Targeting Sigma Receptors for the Treatment of Neurodegenerative and Neurodevelopmental Disorders.
Journal
CNS drugs
ISSN: 1179-1934
Titre abrégé: CNS Drugs
Pays: New Zealand
ID NLM: 9431220
Informations de publication
Date de publication:
05 2023
05 2023
Historique:
accepted:
18
04
2023
medline:
29
5
2023
pubmed:
11
5
2023
entrez:
11
5
2023
Statut:
ppublish
Résumé
The sigma-1 receptor is a 223 amino acid-long protein with a recently identified structure. The sigma-2 receptor is a genetically unrelated protein with a similarly shaped binding pocket and acts to influence cellular activities similar to the sigma-1 receptor. Both proteins are highly expressed in neuronal tissues. As such, they have become targets for treating neurological diseases, including Alzheimer's disease (AD), Huntington's disease (HD), Parkinson's disease (PD), multiple sclerosis (MS), Rett syndrome (RS), developmental and epileptic encephalopathies (DEE), and motor neuron disease/amyotrophic lateral sclerosis (MND/ALS). In recent years, there have been many pre-clinical and clinical studies of sigma receptor (1 and 2) ligands for treating neurological disease. Drugs such as blarcamesine, dextromethorphan and pridopidine, which have sigma-1 receptor activity as part of their pharmacological profile, are effective in treating multiple aspects of several neurological diseases. Furthermore, several sigma-2 receptor ligands are under investigation, including CT1812, rivastigmine and SAS0132. This review aims to provide a current and up-to-date analysis of the current clinical and pre-clinical data of drugs with sigma receptor activities for treating neurological disease.
Identifiants
pubmed: 37166702
doi: 10.1007/s40263-023-01007-6
pii: 10.1007/s40263-023-01007-6
pmc: PMC10173947
doi:
Substances chimiques
Receptors, sigma
0
Types de publication
Journal Article
Review
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
399-440Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.
Références
Hanner M, Moebius FF, Flandorfer A, Knaus HG, Striessnig J, Kempner E, et al. Purification, molecular cloning, and expression of the mammalian sigma1-binding site. Proc Natl Acad Sci USA. 1996;93(15):8072–7. https://doi.org/10.1073/pnas.93.15.8072 .
doi: 10.1073/pnas.93.15.8072
pubmed: 8755605
pmcid: 38877
Hayashi T, Su TP. σ-1 Receptors (σ1 binding sites) form raft-like microdomains and target lipid droplets on the endoplasmic reticulum: roles in endoplasmic reticulum lipid compartmentalization and export. J Pharmacol Exp Ther. 2003;306(2):718–25. https://doi.org/10.1124/jpet.103.051284 .
doi: 10.1124/jpet.103.051284
pubmed: 12730355
Hayashi T, Su TP. Regulating ankyrin dynamics: roles of sigma-1 receptors. Proc Natl Acad Sci USA. 2001;98(2):491–6. https://doi.org/10.1073/pnas.021413698 .
doi: 10.1073/pnas.021413698
pubmed: 11149946
pmcid: 14614
Kinoshita M, Matsuoka Y, Suzuki T, Mirrielees J, Yang J. Sigma-1 receptor alters the kinetics of Kv1.3 voltage gated potassium channels but not the sensitivity to receptor ligands. Brain Res. 2012;1452:1–9. https://doi.org/10.1016/j.brainres.2012.02.070 .
doi: 10.1016/j.brainres.2012.02.070
pubmed: 22433979
pmcid: 3670091
Brimson JM, Akula KK, Abbas H, Ferry DR, Kulkarni SK, Russell ST, et al. Simple ammonium salts acting on sigma-1 receptors yield potential treatments for cancer and depression. Sci Rep. 2020;10(1):9251. https://doi.org/10.1038/s41598-020-65849-6 .
doi: 10.1038/s41598-020-65849-6
pubmed: 32514120
pmcid: 7280195
Brimson JM, Brown CA, Safrany ST. Antagonists show GTP-sensitive high-affinity binding to the sigma-1 receptor. Br J Pharmacol. 2011;164(2B):772–80. https://doi.org/10.1111/j.1476-5381.2011.01417.x .
doi: 10.1111/j.1476-5381.2011.01417.x
pubmed: 21486275
pmcid: 3188898
Natsvlishvili N, Goguadze N, Zhuravliova E, Mikeladze D. Sigma-1 receptor directly interacts with Rac1-GTPase in the brain mitochondria. BMC Biochem. 2015;16(1):1–7. https://doi.org/10.1186/s12858-015-0040-y .
doi: 10.1186/s12858-015-0040-y
Fontanilla D, Johannessen M, Hajipour AR, Cozzi NV, Jackson MB, Ruoho AE. The hallucinogen N, N-dimethyltryptamine (DMT) is an endogenous sigma-1 receptor regulator. Science. 2009;323(5916):934–7. https://doi.org/10.1126/science.1166127 .
doi: 10.1126/science.1166127
pubmed: 19213917
pmcid: 2947205
Hayashi T, Su TP. Sigma-1 receptor ligands: potential in the treatment of neuropsychiatric disorders. CNS Drugs. 2004;18(5):269–84. https://doi.org/10.2165/00023210-200418050-00001 .
doi: 10.2165/00023210-200418050-00001
pubmed: 15089113
Ruoho AE, Chu UB, Ramachandran S, Fontanilla D, Mavlyutov T, Hajipour AR. The ligand binding region of the sigma-1 receptor: studies utilizing photoaffinity probes, sphingosine and N-alkylamines. Curr Pharm Des. 2012;18(7):920–9. https://doi.org/10.2174/138161212799436584 .
doi: 10.2174/138161212799436584
pubmed: 22288412
pmcid: 4440231
Vavers E, Zvejniece L, Maurice T, Dambrova M. Allosteric modulators of sigma-1 receptor: a review. Front Pharmacol. 2019;10:223. https://doi.org/10.3389/fphar.2019.00223 .
doi: 10.3389/fphar.2019.00223
pubmed: 30941035
pmcid: 6433746
Hayashi T, Su TP. The sigma receptor: evolution of the concept in neuropsychopharmacology. Curr Neuropharmacol. 2005;3(4):267–80. https://doi.org/10.2174/157015905774322516 .
doi: 10.2174/157015905774322516
pubmed: 18369400
pmcid: 2268997
Quirion R, Chicheportiche R, Contreras PC, Johnson KM, Lodge D, Tam SW, et al. Classification and nomenclature of phencyclidine and sigma receptor sites. Trends Neurosci. 1987;10(11):444–6. https://doi.org/10.1016/0166-2236(87)90094-4 .
doi: 10.1016/0166-2236(87)90094-4
Spruce BA, Campbell LA, McTavish N, Cooper MA, Appleyard MVL, O’Neill M, et al. Small molecule antagonists of the sigma-1 receptor cause selective release of the death program in tumor and self-reliant cells and inhibit tumor growth in vitro and in vivo. Cancer Res. 2004;64(14):4875–86. https://doi.org/10.1158/0008-5472.CAN-03-3180 .
doi: 10.1158/0008-5472.CAN-03-3180
pubmed: 15256458
Wang L, Prescott AR, Spruce BA, Sanderson J, Duncan G. Sigma receptor antagonists inhibit human lens cell growth and induce pigmentation. Invest Ophthalmol Vis Sci. 2005;46(4):1403–8. https://doi.org/10.1167/iovs.04-1209 .
doi: 10.1167/iovs.04-1209
pubmed: 15790908
Hayashi T, Su TP. Sigma-1 receptor chaperones at the ER-mitochondrion interface regulate Ca2+ signaling and cell survival. Cell. 2007;131(3):596–610. https://doi.org/10.1016/j.cell.2007.08.036 .
doi: 10.1016/j.cell.2007.08.036
pubmed: 17981125
Hellewell SB, Bruce A, Feinstein G, Orringer J, Williams W, Bowen WD. Rat liver and kidney contain high densities of σ1 and σ2 receptors: characterization by ligand binding and photoaffinity labeling. Eur J Pharmacol. 1994;268(1):9–18. https://doi.org/10.1016/0922-4106(94)90115-5 .
doi: 10.1016/0922-4106(94)90115-5
pubmed: 7925616
Wolfe SA Jr, Culp SG, De Souza EB. σ-Receptors in endocrine organs: identification, characterization, and autoradiographic localization in rat pituitary, adrenal, testis, and ovary. Endocrinology. 1989;124(3):1160–72. https://doi.org/10.1210/endo-124-3-1160 .
doi: 10.1210/endo-124-3-1160
pubmed: 2537173
Borde P, Cosgrove N, Charmsaz S, Safrany ST, Young L. An investigation of Sigma-1 receptor expression and ligand-induced endoplasmic reticulum stress in breast cancer. Cancer Gene Ther. 2023;30(2):368–74. https://doi.org/10.1038/s41417-022-00552-4 .
doi: 10.1038/s41417-022-00552-4
pubmed: 36352093
Huang YS, Lu HL, Zhang LJ, Wu Z. Sigma-2 receptor ligands and their perspectives in cancer diagnosis and therapy. Med Res Rev. 2014;34(3):532–66. https://doi.org/10.1002/med.21297 .
doi: 10.1002/med.21297
pubmed: 23922215
Nicholson H, Mesangeau C, McCurdy CR, Bowen WD. Sigma-2 receptors play a role in cellular metabolism: stimulation of glycolytic hallmarks by CM764 in human SK-N-SH neuroblastoma. J Pharmacol Exp Ther. 2016;356(2):232–43. https://doi.org/10.1124/jpet.115.228387 .
doi: 10.1124/jpet.115.228387
pubmed: 26574517
pmcid: 4746495
Rousseaux CG, Greene SF. Sigma receptors [σRs]: biology in normal and diseased states. J Recept Signal Transduct Res. 2016;36(4):327–88. https://doi.org/10.3109/10799893.2015.1015737 .
doi: 10.3109/10799893.2015.1015737
pubmed: 26056947
Liu C, Yu CF, Wang SC, Li HY, Lin CM, Wang HH, et al. Sigma-2 receptor/TMEM97 agonist PB221 as an alternative drug for brain tumor. BMC Cancer. 2019;19(1):473. https://doi.org/10.1186/s12885-019-5700-7 .
doi: 10.1186/s12885-019-5700-7
pubmed: 31109310
pmcid: 6528305
Yang K, Wang C, Sun T. The roles of intracellular chaperone proteins, sigma receptors, in Parkinson’s disease (PD) and major depressive disorder (MDD). Front Pharmacol. 2019;10:528. https://doi.org/10.3389/fphar.2019.00528 .
doi: 10.3389/fphar.2019.00528
pubmed: 31178723
pmcid: 6537631
Georgiadis MO, Karoutzou O, Foscolos AS, Papanastasiou I. Sigma receptor (σR) ligands with antiproliferative and anticancer activity. Molecules. 2017;22:9. https://doi.org/10.3390/molecules22091408 .
doi: 10.3390/molecules22091408
Gebreselassie D, Bowen WD. Sigma-2 receptors are specifically localized to lipid rafts in rat liver membranes. Eur J Pharmacol. 2004;493(1–3):19–28. https://doi.org/10.1016/j.ejphar.2004.04.005 .
doi: 10.1016/j.ejphar.2004.04.005
pubmed: 15189760
Munro S. Lipid rafts: elusive or illusive? Cell. 2003;115(4):377–88. https://doi.org/10.1016/S0092-8674(03)00882-1 .
doi: 10.1016/S0092-8674(03)00882-1
pubmed: 14622593
Alon A, Lyu J, Braz JM, Tummino TA, Craik V, O’Meara MJ, et al. Structures of the σ2 receptor enable docking for bioactive ligand discovery. Nature. 2021;600(7890):759–64. https://doi.org/10.1038/s41586-021-04175-x .
doi: 10.1038/s41586-021-04175-x
pubmed: 34880501
pmcid: 8867396
Terada K, Migita K, Matsushima Y, Kamei C. Sigma-2 receptor as a potential therapeutic target for treating central nervous system disorders. Neural Regen Res. 2019;14(11):1893–4. https://doi.org/10.4103/1673-5374.259609 .
doi: 10.4103/1673-5374.259609
pubmed: 31290438
pmcid: 6676876
Abate C, Niso M, Berardi F. Sigma-2 receptor: past, present and perspectives on multiple therapeutic exploitations. Future Med Chem. 2018;10(16):1997–2018. https://doi.org/10.4155/fmc-2018-0072 .
doi: 10.4155/fmc-2018-0072
pubmed: 29966437
Cantonero C, Camello PJ, Abate C, Berardi F, Salido GM, Rosado JA, et al. NO1, a new Sigma 2 receptor/TMEM97 fluorescent ligand, downregulates SOCE and promotes apoptosis in the triple negative breast cancer cell lines. Cancers (Basel). 2020;12(2):257. https://doi.org/10.3390/cancers12020257 .
doi: 10.3390/cancers12020257
pubmed: 31973006
pmcid: 7072710
Zeng C, Vangveravong S, McDunn JE, Hawkins WG, Mach RH. Sigma-2 receptor ligand as a novel method for delivering a SMAC mimetic drug for treating ovarian cancer. Br J Cancer. 2013;109(9):2368–77. https://doi.org/10.1038/bjc.2013.593 .
doi: 10.1038/bjc.2013.593
pubmed: 24104966
pmcid: 3817331
Zeng C, Riad A, Mach RH. The biological function of Sigma-2 receptor/TMEM97 and its utility in PET imaging studies in cancer. Cancers (Basel). 2020;12(7):1877. https://doi.org/10.3390/cancers12071877 .
doi: 10.3390/cancers12071877
pubmed: 32668577
pmcid: 7409002
2021 Alzheimer's disease facts and figures. Alzheimers Dement. 2021;17(3):327–406. https://doi.org/10.1002/alz.12328 .
Querfurth HW, LaFerla FM. Alzheimer’s disease. N Engl J Med. 2010;362(4):329–44. https://doi.org/10.1056/NEJMra0909142 .
doi: 10.1056/NEJMra0909142
pubmed: 20107219
Hyman BT. Amyloid-dependent and amyloid-independent stages of Alzheimer disease. Arch Neurol. 2011;68(8):1062–4. https://doi.org/10.1001/archneurol.2011.70 .
doi: 10.1001/archneurol.2011.70
pubmed: 21482918
Soria Lopez JA, González HM, Léger GC. Alzheimer’s disease. Handb Clin Neurol. 2019;167:231–55. https://doi.org/10.1016/b978-0-12-804766-8.00013-3 .
doi: 10.1016/b978-0-12-804766-8.00013-3
pubmed: 31753135
Hampel H, Caraci F, Cuello AC, Caruso G, Nisticò R, Corbo M, et al. A path toward precision medicine for neuroinflammatory mechanisms in Alzheimer’s disease. Front Immunol. 2020;11:456. https://doi.org/10.3389/fimmu.2020.00456 .
doi: 10.3389/fimmu.2020.00456
pubmed: 32296418
pmcid: 7137904
Johnson ECB, Dammer EB, Duong DM, Ping L, Zhou M, Yin L, et al. Large-scale proteomic analysis of Alzheimer’s disease brain and cerebrospinal fluid reveals early changes in energy metabolism associated with microglia and astrocyte activation. Nat Med. 2020;26(5):769–80. https://doi.org/10.1038/s41591-020-0815-6 .
doi: 10.1038/s41591-020-0815-6
pubmed: 32284590
pmcid: 7405761
Sánchez-Fernández C, Entrena JM, Baeyens JM, Cobos EJ. Sigma-1 receptor antagonists: a new class of neuromodulatory analgesics. Adv Exp Med Biol. 2017;964:109–32. https://doi.org/10.1007/978-3-319-50174-1_9 .
doi: 10.1007/978-3-319-50174-1_9
pubmed: 28315268
Su TP, Hayashi T. Understanding the molecular mechanism of sigma-1 receptors: towards a hypothesis that sigma-1 receptors are intracellular amplifiers for signal transduction. Curr Med Chem. 2003;10(20):2073–80. https://doi.org/10.2174/0929867033456783 .
doi: 10.2174/0929867033456783
pubmed: 12871086
De B, Nadal X, Portillo-salido E, Sánchez-arroyos R, Ovalle S, Palacios G, et al. Sigma-1 receptors regulate activity-induced spinal sensitization and neuropathic pain after peripheral nerve injury. Pain. 2009;145(3):294–303. https://doi.org/10.1016/j.pain.2009.05.013 .
doi: 10.1016/j.pain.2009.05.013
Nieto FR, Cendán CM, Sánchez-Fernández C, Cobos EJ, Entrena JM, Tejada MA, et al. Role of sigma-1 receptors in paclitaxel-induced neuropathic pain in mice. J Pain. 2012;13(11):1107–21. https://doi.org/10.1016/j.jpain.2012.08.006 .
doi: 10.1016/j.jpain.2012.08.006
pubmed: 23063344
Zamanillo D, Romero L, Merlos M, Vela JM. Sigma 1 receptor: a new therapeutic target for pain. Eur J Pharmacol. 2013;716(1–3):78–93. https://doi.org/10.1016/j.ejphar.2013.01.068 .
doi: 10.1016/j.ejphar.2013.01.068
pubmed: 23500210
Kawamura K, Kimura Y, Tsukada H, Kobayashi T, Nishiyama S, Kakiuchi T, et al. An increase of sigma1 receptors in the aged monkey brain. Neurobiol Aging. 2003;24(5):745–52. https://doi.org/10.1016/S0197-4580(02)00152-5 .
doi: 10.1016/S0197-4580(02)00152-5
pubmed: 12885582
Wallace DR, Mactutus CF, Booze RM. Sigma binding sites identified by [3H] DTG are elevated in aged Fischer-344× Brown Norway (F1) rats. Synapse. 2000;35(4):311–3. https://doi.org/10.1002/(SICI)1098-2396(20000315)35:4%3c311::AID-SYN9%3e3.0.CO;2-5 .
doi: 10.1002/(SICI)1098-2396(20000315)35:4<311::AID-SYN9>3.0.CO;2-5
pubmed: 10657041
Ishiwata K, Kobayashi T, Kawamura K, Matsuno K. Age-related changes of the binding of [3H] SA4503 to sigma1 receptors in the rat brain. Ann Nucl Med. 2003;17(1):73–7. https://doi.org/10.1007/BF02988264 .
doi: 10.1007/BF02988264
pubmed: 12691135
Horsager J, Fedorova TD, Berge NV, Klinge MW, Knudsen K, Hansen AK, et al. Cardiac 11C-donepezil binding increases with age in healthy humans: potentially signifying Sigma-1 receptor upregulation. J Cardiovasc Pharmacol Ther. 2019;24(4):365–70. https://doi.org/10.1177/1074248419838509 .
doi: 10.1177/1074248419838509
pubmed: 30913922
Norbury R, Travis MJ, Erlandsson K, Waddington W, Owens J, Pimlott S, et al. In vivo imaging of muscarinic receptors in the aging female brain with (R, R)[123I]-I-QNB and single photon emission tomography. Exp Gerontol. 2005;40(3):137–45. https://doi.org/10.1016/j.exger.2004.10.002 .
doi: 10.1016/j.exger.2004.10.002
pubmed: 15763390
Sheline YI, Mintun MA, Moerlein SM, Snyder AZ. Greater loss of 5-HT2A receptors in midlife than in late life. Am J Psychiatry. 2002;159(3):430–5. https://doi.org/10.1176/appi.ajp.159.3.430 .
doi: 10.1176/appi.ajp.159.3.430
pubmed: 11870007
Inoue M, Suhara T, Sudo Y, Okubo Y, Yasuno F, Kishimoto T, et al. Age-related reduction of extrastriatal dopamine D2 receptor measured by PET. Life Sci. 2001;69(9):1079–84. https://doi.org/10.1016/s0024-3205(01)01205-x .
doi: 10.1016/s0024-3205(01)01205-x
pubmed: 11508650
Brimson JM, Brimson S, Chomchoei C, Tencomnao T. Using Sigma-ligands as part of a multi-receptor approach to target diseases of the brain. Expert Opin Ther Targets. 2020;24(10):1009–28. https://doi.org/10.1080/14728222.2020.1805435 .
doi: 10.1080/14728222.2020.1805435
pubmed: 32746649
Prasanth MI, Malar D, Tencomnao T, Brimson J. The emerging role of the sigma-1 receptor in autophagy: hand-in-hand targets for the treatment of Alzheimer’s Disease. Expert Opin Ther Targets. 2021;25(5):401–14. https://doi.org/10.1080/14728222.2021.1939681 .
doi: 10.1080/14728222.2021.1939681
pubmed: 34110944
Mishina M, Ohyama M, Ishii K, Kitamura S, Kimura Y, Oda K, et al. Low density of sigma 1 receptors in early Alzheimer’s disease. Ann Nucl Med. 2008;22(3):151–6. https://doi.org/10.1007/s12149-007-0094-z .
doi: 10.1007/s12149-007-0094-z
pubmed: 18498028
Minoshima S, Giordani B, Berent S, Frey KA, Foster NL, Kuhl DE. Metabolic reduction in the posterior cingulate cortex in very early Alzheimer’s disease. Ann Neurol. 1997;42(1):85–94. https://doi.org/10.1002/ana.410420114 .
doi: 10.1002/ana.410420114
pubmed: 9225689
Uchida N, Ujike H, Tanaka Y, Sakai A, Yamamoto M, Fujisawa Y, et al. A variant of the sigma receptor type-1 gene is a protective factor for Alzheimer disease. Am J Geriatr Psychiatry. 2005;13(12):1062–6. https://doi.org/10.1176/appi.ajgp.13.12.1062 .
doi: 10.1176/appi.ajgp.13.12.1062
pubmed: 16319298
Maruszak A, Safranow K, Gacia M, Gabryelewicz T, Słowik A, Styczyńska M, et al. Sigma receptor type 1 gene variation in a group of polish patients with Alzheimer’s disease and mild cognitive impairment. Dement Geriatr Cogn Disord. 2007;23(6):432–8. https://doi.org/10.1159/000101990 .
doi: 10.1159/000101990
pubmed: 17457031
Huang Y, Zheng L, Halliday G, Dobson-Stone C, Wang Y, Tang H-D, et al. Genetic polymorphisms in sigma-1 receptor and apolipoprotein E interact to influence the severity of Alzheimer’s disease. Curr Alzheimer Res. 2011;8(7):765–70. https://doi.org/10.2174/156720511797633232 .
doi: 10.2174/156720511797633232
pubmed: 21605063
Feher A, Juhasz A, Laszlo A, Kalman J Jr, Pakaski M, Kalman J, et al. Association between a variant of the sigma-1 receptor gene and Alzheimer’s disease. Neurosci Lett. 2012;517(2):136–9. https://doi.org/10.1016/j.neulet.2012.04.046 .
doi: 10.1016/j.neulet.2012.04.046
pubmed: 22561649
Jin JL, Fang M, Zhao YX, Liu XY. Roles of sigma-1 receptors in Alzheimer’s disease. Int J Clin Exp Med. 2015;8(4):4808–20.
pubmed: 26131055
pmcid: 4484039
Tsai SY, Hayashi T, Harvey BK, Wang Y, Wu WW, Shen RF, et al. Sigma-1 receptors regulate hippocampal dendritic spine formation via a free radical-sensitive mechanism involving Rac1•GTP pathway. Proc Natl Acad Sci USA. 2009;106(52):22468–73. https://doi.org/10.1073/pnas.0909089106 .
doi: 10.1073/pnas.0909089106
pubmed: 20018732
pmcid: 2792161
Fisher A, Bezprozvanny I, Wu L, Ryskamp DA, Bar-Ner N, Natan N, et al. AF710B, a novel M1/σ1 agonist with therapeutic efficacy in animal models of Alzheimer’s disease. Neurodegener Dis. 2016;16(1–2):95–110. https://doi.org/10.1159/000440864 .
doi: 10.1159/000440864
pubmed: 26606130
Ryskamp D, Wu L, Wu J, Kim D, Rammes G, Geva M, et al. Pridopidine stabilizes mushroom spines in mouse models of Alzheimer’s disease by acting on the sigma-1 receptor. Neurobiol Dis. 2019;124:489–504. https://doi.org/10.1016/j.nbd.2018.12.022 .
doi: 10.1016/j.nbd.2018.12.022
pubmed: 30594810
Tsai SYA, Pokrass MJ, Klauer NR, Nohara H, Su TP. Sigma-1 receptor regulates Tau phosphorylation and axon extension by shaping p35 turnover via myristic acid. Proc Natl Acad Sci USA. 2015;112(21):6742–7. https://doi.org/10.1073/pnas.1422001112 .
doi: 10.1073/pnas.1422001112
pubmed: 25964330
pmcid: 4450430
Christ MG, Huesmann H, Nagel H, Kern A, Behl C. Sigma-1 receptor activation induces autophagy and increases proteostasis capacity in vitro and in vivo. Cells. 2019;8(3):211. https://doi.org/10.3390/cells8030211 .
doi: 10.3390/cells8030211
pubmed: 30832324
pmcid: 6468724
Romeo MA, Faggioni A, Cirone M. Could autophagy dysregulation link neurotropic viruses to Alzheimer’s disease? Neural Regen Res. 2019;14(9):1503–6. https://doi.org/10.4103/1673-5374.253508 .
doi: 10.4103/1673-5374.253508
pubmed: 31089040
pmcid: 6557098
McBrayer M, Nixon RA. Lysosome and calcium dysregulation in Alzheimer’s disease: partners in crime. Biochem Soc Trans. 2013;41(6):1495–502. https://doi.org/10.1042/BST20130201 .
doi: 10.1042/BST20130201
pubmed: 24256243
pmcid: 3960943
Uddin MS, Stachowiak A, Mamun AA, Tzvetkov NT, Takeda S, Atanasov AG, et al. Autophagy and Alzheimer’s disease: from molecular mechanisms to therapeutic implications. Front Aging Neurosci. 2018;10:04. https://doi.org/10.3389/fnagi.2018.00004 .
doi: 10.3389/fnagi.2018.00004
pubmed: 29441009
pmcid: 5797541
Callens M, Loncke J, Bultynck G. Dysregulated Ca2+ homeostasis as a central theme in neurodegeneration: lessons from Alzheimer’s disease and Wolfram syndrome. Cells. 2022;11(12):1963. https://doi.org/10.3390/cells11121963 .
doi: 10.3390/cells11121963
pubmed: 35741091
pmcid: 9221778
Holmes C, Boche D, Wilkinson D, Yadegarfar G, Hopkins V, Bayer A, et al. Long-term effects of Aβ42 immunisation in Alzheimer’s disease: follow-up of a randomised, placebo-controlled phase I trial. Lancet. 2008;372(9634):216–23. https://doi.org/10.1016/S0140-6736(08)61075-2 .
doi: 10.1016/S0140-6736(08)61075-2
pubmed: 18640458
van Dyck CH, Swanson CJ, Aisen P, Bateman RJ, Chen C, Gee M, et al. Lecanemab in early Alzheimer’s disease. N Engl J Med. 2023;388(1):9–21. https://doi.org/10.1056/NEJMoa2212948 .
doi: 10.1056/NEJMoa2212948
pubmed: 36449413
Lacor PN, Buniel MC, Furlow PW, Clemente AS, Velasco PT, Wood M, et al. Aβ oligomer-induced aberrations in synapse composition, shape, and density provide a molecular basis for loss of connectivity in Alzheimer’s disease. J Neurosci. 2007;27(4):796–807. https://doi.org/10.1523/JNEUROSCI.3501-06.2007 .
doi: 10.1523/JNEUROSCI.3501-06.2007
pubmed: 17251419
pmcid: 6672917
Pannuzzo M. On the physiological/pathological link between Aβ peptide, cholesterol, calcium ions and membrane deformation: a molecular dynamics study. Biochim Biophys Acta. 2016;1858(6):1380–9. https://doi.org/10.1016/j.bbamem.2016.03.018 .
doi: 10.1016/j.bbamem.2016.03.018
pubmed: 27003127
Games D, Adams D, Alessandrini R, Barbour R, Borthelette P, Blackwell C, et al. Alzheimer-type neuropathology in transgenic mice overexpressing V717F β-amyloid precursor protein. Nature. 1995;373(6514):523–7. https://doi.org/10.1038/373523a0 .
doi: 10.1038/373523a0
pubmed: 7845465
Brimson JM. The Pharmacology of the Sigma-1 Receptor [Doctoral Thesis]. In: The University of Bath online repository. 2010. http://opus.bath.ac.uk/19712/ . Accessed 1 Dec 2022.
Katnik C, Guerrero WR, Pennypacker KR, Herrera Y, Cuevas J. Sigma-1 receptor activation prevents intracellular calcium dysregulation in cortical neurons during in vitro ischemia. J Pharmacol Exp Ther. 2006;319(3):1355–65. https://doi.org/10.1124/jpet.106.107557 .
doi: 10.1124/jpet.106.107557
pubmed: 16988055
Delprat B, Crouzier L, Su TP, Maurice T. At the crossing of ER stress and MAMs: a key role of sigma-1 receptor? Adv Exp Med Biol. 2020;1131:699–718. https://doi.org/10.1007/978-3-030-12457-1_2878 .
doi: 10.1007/978-3-030-12457-1_2878
pubmed: 31646531
Hayashi T, Rizzuto R, Hajnoczky G, Su TP. MAM: more than just a housekeeper. Trends Cell Biol. 2009;19(2):81–8. https://doi.org/10.1016/j.tcb.2008.12.00279 .
doi: 10.1016/j.tcb.2008.12.00279
pubmed: 19144519
pmcid: 2750097
Scheffer IE, Berkovic S, Capovilla G, Connolly MB, French J, Guilhoto L, et al. ILAE classification of the epilepsies: position paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017;58(4):512–21. https://doi.org/10.1111/epi.13709 .
doi: 10.1111/epi.13709
pubmed: 28276062
pmcid: 5386840
Specchio N, Curatolo P. Developmental and epileptic encephalopathies: what we do and do not know. Brain. 2021;144(1):32–43. https://doi.org/10.1093/brain/awaa371 .
doi: 10.1093/brain/awaa371
pubmed: 33279965
Raga S, Specchio N, Rheims S, Wilmshurst JM. Developmental and epileptic encephalopathies: recognition and approaches to care. Epileptic Disord. 2021;23(1):40–52. https://doi.org/10.1684/epd.2021.1244 .
doi: 10.1684/epd.2021.1244
pubmed: 33632673
Scheffer IE, Liao J. Deciphering the concepts behind “Epileptic encephalopathy” and “Developmental and epileptic encephalopathy.” Eur J Paediatr Neurol. 2020;24:11–4. https://doi.org/10.1016/j.ejpn.2019.12.023 .
doi: 10.1016/j.ejpn.2019.12.023
pubmed: 31926847
Trivisano M, Specchio N. What are the epileptic encephalopathies? Curr Opin Neurol. 2020;33(2):179–84. https://doi.org/10.1097/wco.0000000000000793 .
doi: 10.1097/wco.0000000000000793
pubmed: 32049741
EPX-100 (Clemizole Hydrochloride) as add-on therapy to control convulsive seizures in patients with Dravet syndrome (ARGUS). In: NIH U.S. National Library of Medicine. 2020. https://clinicaltrials.gov/ct2/show/NCT04462770. Accessed 1 Dec 2022.
Griffin A, Hamling KR, Knupp K, Hong S, Lee LP, Baraban SC. Clemizole and modulators of serotonin signalling suppress seizures in Dravet syndrome. Brain. 2017;140(3):669–83. https://doi.org/10.1093/brain/aww342 .
doi: 10.1093/brain/aww342
pubmed: 28073790
pmcid: 6075536
Vasquez A, Buraniqi E, Wirrell EC. New and emerging pharmacologic treatments for developmental and epileptic encephalopathies. Curr Opin Neurol. 2022;35(2):145–54. https://doi.org/10.1097/wco.0000000000001029 .
doi: 10.1097/wco.0000000000001029
pubmed: 35102126
Miziak B, Czuczwar S. Advances in the design and discovery of novel small molecule drugs for the treatment of Dravet Syndrome. Expert Opin Drug Discov. 2021;16(5):579–93. https://doi.org/10.1080/17460441.2021.1857722 .
doi: 10.1080/17460441.2021.1857722
pubmed: 33275464
Samanta D. Changing landscape of Dravet syndrome management: an overview. Neuropediatrics. 2020;51(2):135–45. https://doi.org/10.1055/s-0040-1701694 .
doi: 10.1055/s-0040-1701694
pubmed: 32079034
Martin P, Reeder T, Sourbron J, de Witte PAM, Gammaitoni AR, Galer BS. An emerging role for Sigma-1 receptors in the treatment of developmental and epileptic encephalopathies. Int J Mol Sci. 2021;22(16):8416. https://doi.org/10.3390/ijms22168416 .
doi: 10.3390/ijms22168416
pubmed: 34445144
pmcid: 8395113
Vavers E, Zvejniece B, Stelfa G, Svalbe B, Vilks K, Kupats E, et al. Genetic inactivation of the sigma-1 chaperone protein results in decreased expression of the R2 subunit of the GABA-B receptor and increased susceptibility to seizures. Neurobiol Dis. 2021;150:105244. https://doi.org/10.1016/j.nbd.2020.105244 .
doi: 10.1016/j.nbd.2020.105244
pubmed: 33385516
Schaffar G, Breuer P, Boteva R, Behrends C, Tzvetkov N, Strippel N, et al. Cellular toxicity of polyglutamine expansion proteins: mechanism of transcription factor deactivation. Mol Cell. 2004;15(1):95–105. https://doi.org/10.1016/j.molcel.2004.06.029 .
doi: 10.1016/j.molcel.2004.06.029
pubmed: 15225551
Martinez-Vicente M, Talloczy Z, Wong E, Tang G, Koga H, Kaushik S, et al. Cargo recognition failure is responsible for inefficient autophagy in Huntington’s disease. Nat Neurosci. 2010;13(5):567–76. https://doi.org/10.1038/nn.2528 .
doi: 10.1038/nn.2528
pubmed: 20383138
pmcid: 2860687
Mochel F, Haller RG. Energy deficit in Huntington disease: why it matters. J Clin Invest. 2011;121(2):493–9. https://doi.org/10.1172/JCI45691 .
doi: 10.1172/JCI45691
pubmed: 21285522
pmcid: 3026743
Caron NS, Wright GEB, Hayden MR. Huntington Disease. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, et al., editors. GeneReviews, University of Washington, Seattle. 1993. https://www.ncbi.nlm.nih.gov/books/NBK1305/ .
Frank S. Treatment of Huntington’s disease. Neurotherapeutics. 2014;11(1):153–60. https://doi.org/10.1007/s13311-013-0244-z .
doi: 10.1007/s13311-013-0244-z
pubmed: 24366610
Miki Y, Tanji K, Mori F, Wakabayashi K. Sigma-1 receptor is involved in degradation of intranuclear inclusions in a cellular model of Huntington’s disease. Neurobiol Dis. 2015;74:25–31. https://doi.org/10.1016/j.nbd.2014.11.005 .
doi: 10.1016/j.nbd.2014.11.005
pubmed: 25449906
Ryskamp D, Wu J, Geva M, Kusko R, Grossman I, Hayden M, et al. The sigma-1 receptor mediates the beneficial effects of pridopidine in a mouse model of Huntington disease. Neurobiol Dis. 2017;97:46–59. https://doi.org/10.1016/j.nbd.2016.10.006 .
doi: 10.1016/j.nbd.2016.10.006
pubmed: 27818324
Jabłońska M, Grzelakowska K, Wiśniewski B, Mazur E, Leis K, Gałązka P. Pridopidine in the treatment of Huntington’s disease. Rev Neurosci. 2020;31(4):441–51. https://doi.org/10.1515/revneuro-2019-0085 .
doi: 10.1515/revneuro-2019-0085
pubmed: 32083454
Nguyen L, Lucke-Wold BP, Mookerjee SA, Cavendish JZ, Robson MJ, Scandinaro AL, et al. Role of sigma-1 receptors in neurodegenerative diseases. J Pharmacol Sci. 2015;127(1):17–29. https://doi.org/10.1016/j.jphs.2014.12.005 .
doi: 10.1016/j.jphs.2014.12.005
pubmed: 25704014
Swinnen B, Robberecht W. The phenotypic variability of amyotrophic lateral sclerosis. Nat Rev Neurol. 2014;10(11):661–70. https://doi.org/10.1038/nrneurol.2014.184 .
doi: 10.1038/nrneurol.2014.184
pubmed: 25311585
Machts J, Keute M, Kaufmann J, Schreiber S, Kasper E, Petri S, et al. Longitudinal clinical and neuroanatomical correlates of memory impairment in motor neuron disease. Neuroimage Clin. 2021;29:102545. https://doi.org/10.1016/j.nicl.2020.102545 .
doi: 10.1016/j.nicl.2020.102545
pubmed: 33387861
Roggenbuck J, Quick A, Kolb SJ. Genetic testing and genetic counseling for amyotrophic lateral sclerosis: an update for clinicians. Genet Med. 2017;19(3):267–74. https://doi.org/10.1038/gim.2016.107 .
doi: 10.1038/gim.2016.107
pubmed: 27537704
van den Bos MAJ, Geevasinga N, Higashihara M, Menon P, Vucic S. Pathophysiology and diagnosis of ALS: insights from advances in neurophysiological techniques. Int J Mol Sci. 2019;20(11):2818. https://doi.org/10.3390/ijms20112818 .
doi: 10.3390/ijms20112818
pubmed: 31185581
pmcid: 6600525
Bensimon G, Lacomblez L, Meininger V. A controlled trial of riluzole in amyotrophic lateral sclerosis. ALS/Riluzole Study Group. N Engl J Med. 1994;330(9):585–91. https://doi.org/10.1056/nejm199403033300901 .
doi: 10.1056/nejm199403033300901
pubmed: 8302340
Heo YA. Sodium phenylbutyrate and ursodoxicoltaurine: first approval. CNS Drugs. 2022;36(9):1007–13. https://doi.org/10.1007/s40263-022-00945-x .
doi: 10.1007/s40263-022-00945-x
pubmed: 35907175
Jaiswal MK. Riluzole and edaravone: a tale of two amyotrophic lateral sclerosis drugs. Med Res Rev. 2019;39(2):733–48. https://doi.org/10.1002/med.21528 .
doi: 10.1002/med.21528
pubmed: 30101496
Mora JS, Genge A, Chio A, Estol CJ, Chaverri D, Hernández M, et al. Masitinib as an add-on therapy to riluzole in patients with amyotrophic lateral sclerosis: a randomized clinical trial. Amyotroph Lateral Scler Frontotemporal Degener. 2020;21(1–2):5–14. https://doi.org/10.1080/21678421.2019.1632346 .
doi: 10.1080/21678421.2019.1632346
pubmed: 31280619
Latham BD, Oskin DS, Crouch RD, Vergne MJ, Jackson KD. Cytochromes P450 2C8 and 3A catalyze the metabolic activation of the tyrosine kinase inhibitor masitinib. Chem Res Toxicol. 2022;35(9):1467–81. https://doi.org/10.1021/acs.chemrestox.2c00057 .
doi: 10.1021/acs.chemrestox.2c00057
pubmed: 36048877
Casanovas A, Salvany S, Lahoz V, Tarabal O, Piedrafita L, Sabater R, et al. Neuregulin 1-ErbB module in C-bouton synapses on somatic motor neurons: molecular compartmentation and response to peripheral nerve injury. Sci Rep. 2017;7:40155. https://doi.org/10.1038/srep40155 .
doi: 10.1038/srep40155
pubmed: 28065942
pmcid: 5220293
Herrando-Grabulosa M, Gaja-Capdevila N, Vela JM, Navarro X. Sigma 1 receptor as a therapeutic target for amyotrophic lateral sclerosis. Br J Pharmacol. 2021;178(6):1336–52. https://doi.org/10.1111/bph.15224 .
doi: 10.1111/bph.15224
pubmed: 32761823
Mavlyutov TA, Epstein ML, Liu P, Verbny YI, Ziskind-Conhaim L, Ruoho AE. Development of the sigma-1 receptor in C-terminals of motoneurons and colocalization with the N, N′-dimethyltryptamine forming enzyme, indole-N-methyl transferase. Neuroscience. 2012;206:60–8. https://doi.org/10.1016/j.neuroscience.2011.12.040 .
doi: 10.1016/j.neuroscience.2011.12.040
pubmed: 22265729
Mavlyutov TA, Epstein ML, Andersen KA, Ziskind-Conhaim L, Ruoho AE. The sigma-1 receptor is enriched in postsynaptic sites of C-terminals in mouse motoneurons. An anatomical and behavioral study. Neuroscience. 2010;167(2):247–55. https://doi.org/10.1016/j.neuroscience.2010.02.022 .
doi: 10.1016/j.neuroscience.2010.02.022
pubmed: 20167253
Watanabe S, Ilieva H, Tamada H, Nomura H, Komine O, Endo F, et al. Mitochondria-associated membrane collapse is a common pathomechanism in SIGMAR 1-and SOD 1-linked ALS. EMBO Mol Med. 2016;8(12):1421–37. https://doi.org/10.15252/emmm.201606403 .
doi: 10.15252/emmm.201606403
pubmed: 27821430
pmcid: 5167132
Couly S, Khalil B, Viguier V, Roussel J, Maurice T, Liévens J-C. Sigma-1 receptor is a key genetic modulator in amyotrophic lateral sclerosis. Hum Mol Genet. 2020;29(4):529–40. https://doi.org/10.1093/hmg/ddz267 .
doi: 10.1093/hmg/ddz267
pubmed: 31696229
Vollrath J, Sechi A, Dreser A, Katona I, Wiemuth D, Vervoorts J, et al. Loss of function of the ALS protein SigR1 leads to ER pathology associated with defective autophagy and lipid raft disturbances. Cell Death Dis. 2014;5(6):e1290. https://doi.org/10.1038/cddis.2014.243 .
doi: 10.1038/cddis.2014.243
pubmed: 24922074
pmcid: 4611717
Dreser A, Vollrath JT, Sechi A, Johann S, Roos A, Yamoah A, et al. The ALS-linked E102Q mutation in Sigma receptor-1 leads to ER stress-mediated defects in protein homeostasis and dysregulation of RNA-binding proteins. Cell Death Differ. 2017;24(10):1655–71. https://doi.org/10.1038/cdd.2017.88 .
doi: 10.1038/cdd.2017.88
pubmed: 28622300
pmcid: 5596426
Mavlyutov TA, Epstein ML, Verbny YI, Huerta MS, Zaitoun I, Ziskind-Conhaim L, et al. Lack of sigma-1 receptor exacerbates ALS progression in mice. Neuroscience. 2013;240:129–34. https://doi.org/10.1016/j.neuroscience.2013.02.035 .
doi: 10.1016/j.neuroscience.2013.02.035
pubmed: 23458708
Al-Saif A, Al-Mohanna F, Bohlega S. A mutation in sigma-1 receptor causes juvenile amyotrophic lateral sclerosis. Ann Neurol. 2011;70(6):913–9. https://doi.org/10.1002/ana.22534 .
doi: 10.1002/ana.22534
pubmed: 21842496
Fukunaga K, Shinoda Y, Tagashira H. The role of SIGMAR1 gene mutation and mitochondrial dysfunction in amyotrophic lateral sclerosis. J Pharmacol Sci. 2015;127(1):36–41. https://doi.org/10.1016/j.jphs.2014.12.012 .
doi: 10.1016/j.jphs.2014.12.012
pubmed: 25704016
Barmada SJ, Skibinski G, Korb E, Rao EJ, Wu JY, Finkbeiner S. Cytoplasmic mislocalization of TDP-43 is toxic to neurons and enhanced by a mutation associated with familial amyotrophic lateral sclerosis. J Neurosci. 2010;30(2):639–49. https://doi.org/10.1523/JNEUROSCI.4988-09.2010 .
doi: 10.1523/JNEUROSCI.4988-09.2010
pubmed: 20071528
pmcid: 2821110
Prasad A, Bharathi V, Sivalingam V, Girdhar A, Patel BK. Molecular mechanisms of TDP-43 misfolding and pathology in amyotrophic lateral sclerosis. Front Mol Neurosci. 2019;12:25. https://doi.org/10.3389/fnmol.2019.00025 .
doi: 10.3389/fnmol.2019.00025
pubmed: 30837838
pmcid: 6382748
Brettschneider J, Del Tredici K, Toledo JB, Robinson JL, Irwin DJ, Grossman M, et al. Stages of pTDP-43 pathology in amyotrophic lateral sclerosis. Ann Neurol. 2013;74(1):20–38. https://doi.org/10.1002/ana.23937 .
doi: 10.1002/ana.23937
pubmed: 23686809
pmcid: 3785076
Lee P-T, Liévens J-C, Wang S-M, Chuang J-Y, Khalil B, Wu H-E, et al. Sigma-1 receptor chaperones rescue nucleocytoplasmic transport deficit seen in cellular and Drosophila ALS/FTD models. Nat Commun. 2020;11(1):5580. https://doi.org/10.1038/s41467-020-19396-3 .
doi: 10.1038/s41467-020-19396-3
pubmed: 33149115
pmcid: 7642387
Frischer JM, Bramow S, Dal-Bianco A, Lucchinetti CF, Rauschka H, Schmidbauer M, et al. The relation between inflammation and neurodegeneration in multiple sclerosis brains. Brain. 2009;132(Pt 5):1175–89. https://doi.org/10.1093/brain/awp070 .
doi: 10.1093/brain/awp070
pubmed: 19339255
pmcid: 2677799
McGinley MP, Goldschmidt CH, Rae-Grant AD. Diagnosis and treatment of multiple sclerosis: a review. JAMA. 2021;325(8):765–79. https://doi.org/10.1001/jama.2020.26858 .
doi: 10.1001/jama.2020.26858
pubmed: 33620411
Krupp L. Fatigue is intrinsic to multiple sclerosis (MS) and is the most commonly reported symptom of the disease. Mult Scler. 2006;12(4):367–8. https://doi.org/10.1191/135248506ms1373ed .
doi: 10.1191/135248506ms1373ed
pubmed: 16900749
Braley TJ, Chervin RD. Fatigue in multiple sclerosis: mechanisms, evaluation, and treatment. Sleep. 2010;33(8):1061–7. https://doi.org/10.1093/sleep/33.8.1061 .
doi: 10.1093/sleep/33.8.1061
pubmed: 20815187
pmcid: 2910465
Jacobs LD, Beck RW, Simon JH, Kinkel RP, Brownscheidle CM, Murray TJ, et al. Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. CHAMPS Study Group. N Engl J Med. 2000;343(13):898–904. https://doi.org/10.1056/nejm200009283431301 .
doi: 10.1056/nejm200009283431301
pubmed: 11006365
Lycke J. Monoclonal antibody therapies for the treatment of relapsing-remitting multiple sclerosis: differentiating mechanisms and clinical outcomes. Ther Adv Neurol Disord. 2015;8(6):274–93. https://doi.org/10.1177/1756285615605429 .
doi: 10.1177/1756285615605429
pubmed: 26600872
pmcid: 4643868
Kappos L, Radue EW, O’Connor P, Polman C, Hohlfeld R, Calabresi P, et al. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med. 2010;362(5):387–401. https://doi.org/10.1056/NEJMoa0909494 .
doi: 10.1056/NEJMoa0909494
pubmed: 20089952
Kappos L, Bar-Or A, Cree BAC, Fox RJ, Giovannoni G, Gold R, et al. Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study. Lancet. 2018;391(10127):1263–73. https://doi.org/10.1016/s0140-6736(18)30475-6 .
doi: 10.1016/s0140-6736(18)30475-6
pubmed: 29576505
Comi G, Kappos L, Selmaj KW, Bar-Or A, Arnold DL, Steinman L, et al. Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis (SUNBEAM): a multicentre, randomised, minimum 12-month, phase 3 trial. Lancet Neurol. 2019;18(11):1009–20. https://doi.org/10.1016/s1474-4422(19)30239-x .
doi: 10.1016/s1474-4422(19)30239-x
pubmed: 31492651
Johnson KP, Brooks BR, Cohen JA, Ford CC, Goldstein J, Lisak RP, et al. Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase III multicenter, double-blind placebo-controlled trial. The Copolymer 1 Multiple Sclerosis Study Group. Neurology. 1995;45(7):1268–76. https://doi.org/10.1212/wnl.45.7.1268 .
doi: 10.1212/wnl.45.7.1268
pubmed: 7617181
Confavreux C, O’Connor P, Comi G, Freedman MS, Miller AE, Olsson TP, et al. Oral teriflunomide for patients with relapsing multiple sclerosis (TOWER): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Neurol. 2014;13(3):247–56. https://doi.org/10.1016/s1474-4422(13)70308-9 .
doi: 10.1016/s1474-4422(13)70308-9
pubmed: 24461574
Giovannoni G, Comi G, Cook S, Rammohan K, Rieckmann P, Soelberg Sørensen P, et al. A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis. N Engl J Med. 2010;362(5):416–26. https://doi.org/10.1056/NEJMoa0902533 .
doi: 10.1056/NEJMoa0902533
pubmed: 20089960
Palacios G, Muro A, Verdú E, Pumarola M, Vela JM. Immunohistochemical localization of the sigma1 receptor in Schwann cells of rat sciatic nerve. Brain Res. 2004;1007(1–2):65–70. https://doi.org/10.1016/j.brainres.2004.02.013 .
doi: 10.1016/j.brainres.2004.02.013
pubmed: 15064136
Hayashi T, Su T-P. Sigma-1 receptors at galactosylceramide-enriched lipid microdomains regulate oligodendrocyte differentiation. Proc Natl Acad Sci USA. 2004;101(41):14949–54. https://doi.org/10.1073/pnas.0402890101 .
doi: 10.1073/pnas.0402890101
pubmed: 15466698
pmcid: 522002
Zhemkov V, Geva M, Hayden MR, Bezprozvanny I. Sigma-1 receptor (S1R) interaction with cholesterol: mechanisms of S1R activation and its role in neurodegenerative diseases. Int J Mol Sci. 2021;22(8):4082. https://doi.org/10.3390/ijms22084082 .
doi: 10.3390/ijms22084082
pubmed: 33920913
pmcid: 8071319
Berghoff SA, Spieth L, Saher G. Local cholesterol metabolism orchestrates remyelination. Trends Neurosci. 2022;45(4):272–83. https://doi.org/10.1016/j.tins.2022.01.001 .
doi: 10.1016/j.tins.2022.01.001
pubmed: 35153084
Kenche H, Singh M, Smith J, Shen K. Neuronal mitochondrial dysfunction in a cellular model of circadian rhythm disruption is rescued by donepezil. Biochem Biophys Res Commun. 2021;567:56–62. https://doi.org/10.1016/j.bbrc.2021.06.029 .
doi: 10.1016/j.bbrc.2021.06.029
pubmed: 34144501
Oxombre B, Lee-Chang C, Duhamel A, Toussaint M, Giroux M, Donnier-Maréchal M, et al. High-affinity σ1 protein agonist reduces clinical and pathological signs of experimental autoimmune encephalomyelitis. Br J Pharmacol. 2015;172(7):1769–82. https://doi.org/10.1111/bph.13037 .
doi: 10.1111/bph.13037
pubmed: 25521311
pmcid: 4376455
Lotankar S, Prabhavalkar KS, Bhatt LK. Biomarkers for Parkinson’s disease: recent advancement. Neurosci Bull. 2017;33(5):585–97. https://doi.org/10.1007/s12264-017-0183-5 .
doi: 10.1007/s12264-017-0183-5
pubmed: 28936761
pmcid: 5636742
Chen-Plotkin AS, Albin R, Alcalay R, Babcock D, Bajaj V, Bowman D, et al. Finding useful biomarkers for Parkinson’s disease. Sci Transl Med. 2018;10(454):eaam6003. https://doi.org/10.1126/scitranslmed.aam6003 .
doi: 10.1126/scitranslmed.aam6003
pubmed: 30111645
pmcid: 6097233
Li T, Le W. Biomarkers for Parkinson’s disease: how good are they? Neurosci Bull. 2020;36(2):183–94. https://doi.org/10.1007/s12264-019-00433-1 .
doi: 10.1007/s12264-019-00433-1
pubmed: 31646434
Bloem BR, Okun MS, Klein C. Parkinson’s disease. Lancet. 2021;397(10291):2284–303. https://doi.org/10.1016/s0140-6736(21)00218-x .
doi: 10.1016/s0140-6736(21)00218-x
pubmed: 33848468
Parkinson disease. In: World Health Organization website. 2022. https://www.who.int/news-room/fact-sheets/detail/parkinson-disease . Accessed 1 Dec 2022.
LeWitt PA. Levodopa therapy for Parkinson’s disease: pharmacokinetics and pharmacodynamics. Mov Disord. 2015;30(1):64–72. https://doi.org/10.1002/mds.26082 .
doi: 10.1002/mds.26082
pubmed: 25449210
Nonnekes J, Timmer MH, de Vries NM, Rascol O, Helmich RC, Bloem BR. Unmasking levodopa resistance in Parkinson’s disease. Mov Disord. 2016;31(11):1602–9. https://doi.org/10.1002/mds.26712 .
doi: 10.1002/mds.26712
pubmed: 27430479
Walker Z, Possin KL, Boeve BF, Aarsland D. Lewy body dementias. Lancet. 2015;386(10004):1683–97. https://doi.org/10.1016/S0140-6736(15)00462-6 .
doi: 10.1016/S0140-6736(15)00462-6
pubmed: 26595642
pmcid: 5792067
Aarsland D, Andersen K, Larsen J, Lolk A, Nielsen H, Kragh-Sørensen P. Risk of dementia in Parkinson’s disease: a community-based, prospective study. Neurology. 2001;56(6):730–6. https://doi.org/10.1212/wnl.56.6.730 .
doi: 10.1212/wnl.56.6.730
pubmed: 11274306
Mishina M, Ishiwata K, Ishii K, Kitamura S, Kimura Y, Kawamura K, et al. Function of sigma 1 receptors in Parkinson’s disease. Acta Neurol Scand. 2005;112(2):103–7. https://doi.org/10.1111/j.1600-0404.2005.00432.x .
doi: 10.1111/j.1600-0404.2005.00432.x
pubmed: 16008536
Hong J, Wang L, Zhang T, Zhang B, Chen L. Sigma-1 receptor knockout increases α-synuclein aggregation and phosphorylation with loss of dopaminergic neurons in substantia nigra. Neurobiol Aging. 2017;59:171–83. https://doi.org/10.1016/j.neurobiolaging.2017.08.007 .
doi: 10.1016/j.neurobiolaging.2017.08.007
pubmed: 28870519
Luo Y, Roth GS. The roles of dopamine oxidative stress and dopamine receptor signaling in aging and age-related neurodegeneration. Antioxid Redox Signal. 2000;2(3):449–60. https://doi.org/10.1089/15230860050192224 .
doi: 10.1089/15230860050192224
pubmed: 11229358
Mori T, Hayashi T, Su TP. Compromising σ-1 receptors at the endoplasmic reticulum render cytotoxicity to physiologically relevant concentrations of dopamine in a nuclear factor-κB/Bcl-2-dependent mechanism: Potential relevance to Parkinson’s disease. J Pharmacol Exp Ther. 2012;341(3):663–71. https://doi.org/10.1124/jpet.111.190868 .
doi: 10.1124/jpet.111.190868
pubmed: 22399814
pmcid: 3362887
Cagnin M, Ozzano M, Bellio N, Fiorentino I, Follo C, Isidoro C. Dopamine induces apoptosis in APPswe-expressing Neuro2A cells following Pepstatin-sensitive proteolysis of APP in acid compartments. Brain Res. 2012;1471:102–17. https://doi.org/10.1016/j.brainres.2012.06.025 .
doi: 10.1016/j.brainres.2012.06.025
pubmed: 22771396
Brimson JM, Safrany ST, Qassam H, Tencomnao T. Dipentylammonium binds to the Sigma-1 receptor and protects against glutamate toxicity, attenuates dopamine toxicity and potentiates neurite outgrowth in various cultured cell lines. Neurotox Res. 2018;34(2):263–72. https://doi.org/10.1007/s12640-018-9883-5 .
doi: 10.1007/s12640-018-9883-5
pubmed: 29589276
Poewe W, Seppi K, Tanner CM, Halliday GM, Brundin P, Volkmann J, et al. Parkinson disease. Nat Rev Dis Primers. 2017;3:17013. https://doi.org/10.1038/nrdp.2017.13 .
doi: 10.1038/nrdp.2017.13
pubmed: 28332488
Jenner P, Olanow CW. Oxidative stress and the pathogenesis of Parkinson’s disease. Neurology. 1996;47(6 Suppl 3):S161–70. https://doi.org/10.1212/wnl.47.6_suppl_3.161s .
doi: 10.1212/wnl.47.6_suppl_3.161s
pubmed: 8959985
Cristóvão AC, Guhathakurta S, Bok E, Je G, Yoo SD, Choi D-H, et al. NADPH oxidase 1 mediates α-synucleinopathy in Parkinson’s disease. J Neurosci. 2012;32(42):14465–77. https://doi.org/10.1523/JNEUROSCI.2246-12.2012 .
doi: 10.1523/JNEUROSCI.2246-12.2012
pubmed: 23077033
pmcid: 3501265
Guo JD, Zhao X, Li Y, Li GR, Liu XL. Damage to dopaminergic neurons by oxidative stress in Parkinson’s disease. Int J Mol Med. 2018;41(4):1817–25. https://doi.org/10.3892/ijmm.2018.3406 .
doi: 10.3892/ijmm.2018.3406
pubmed: 29393357
Pal A, Fontanilla D, Gopalakrishnan A, Chae Y-K, Markley JL, Ruoho AE. The sigma-1 receptor protects against cellular oxidative stress and activates antioxidant response elements. Eur J Pharmacol. 2012;682(1–3):12–20. https://doi.org/10.1016/j.ejphar.2012.01.030 .
doi: 10.1016/j.ejphar.2012.01.030
pubmed: 22381068
pmcid: 3314091
Wang J, Shanmugam A, Markand S, Zorrilla E, Ganapathy V, Smith SB. Sigma 1 receptor regulates the oxidative stress response in primary retinal Müller glial cells via NRF2 signaling and system xc−, the Na+-independent glutamate–cystine exchanger. Free Radic Biol Med. 2015;86:25–36. https://doi.org/10.1016/j.freeradbiomed.2015.04.009 .
doi: 10.1016/j.freeradbiomed.2015.04.009
pubmed: 25920363
pmcid: 4554890
Prasanth MI, Tencomnao T, Brimson JM. The Sigma-1 receptors role in neuroprotection: Comment on Nrf2 as a therapeutic target in ischemic stroke. Expert Opin Ther Targets. 2021;25(7):613–4. https://doi.org/10.1080/14728222.2021.1948016 .
doi: 10.1080/14728222.2021.1948016
pubmed: 34180350
Brimson JM, Prasanth MI, Isidoro C, Sukprasansap M, Tencomnao T. Cleistocalyx nervosum var. paniala seed extracts exhibit sigma-1 antagonist sensitive neuroprotective effects in PC12 cells and protect C. elegans from stress via the SKN-1/NRF-2 pathway. Nutr Healthy Aging. 2021;6(2):131–46. https://doi.org/10.3233/NHA-200108 .
doi: 10.3233/NHA-200108
Brimson JM, Prasanth MI, Malar DS, Verma K, Plaingam W, Tencomnao T. Bacopa monnieri protects neuronal cell line and Caenorhabditis elegans models of Alzheimer’s disease through sigma-1 receptor antagonist sensitive and antioxidant pathways. Nutr Healthy Aging. 2022;7(3):173–96. https://doi.org/10.3233/NHA-220161 .
doi: 10.3233/NHA-220161
Betzer C, Movius AJ, Shi M, Gai W-P, Zhang J, Jensen PH. Identification of synaptosomal proteins binding to monomeric and oligomeric α-synuclein. PLoS ONE. 2015;10(2):e0116473. https://doi.org/10.1371/journal.pone.0116473 .
doi: 10.1371/journal.pone.0116473
pubmed: 25659148
pmcid: 4319895
Schneider JL, Cuervo AM. Autophagy and human disease: emerging themes. Curr Opin Genet Dev. 2014;26:16–23. https://doi.org/10.1016/j.gde.2014.04.003 .
doi: 10.1016/j.gde.2014.04.003
pubmed: 24907664
Vogiatzi T, Xilouri M, Vekrellis K, Stefanis L. Wild type α-synuclein is degraded by chaperone-mediated autophagy and macroautophagy in neuronal cells. J Biol Chem. 2008;283(35):23542–56. https://doi.org/10.1074/jbc.M801992200 .
doi: 10.1074/jbc.M801992200
pubmed: 18566453
pmcid: 2527094
Galvagnion C. The role of lipids interacting with α-synuclein in the pathogenesis of Parkinson’s disease. J Parkinsons Dis. 2017;7(3):433–50. https://doi.org/10.3233/JPD-171103 .
doi: 10.3233/JPD-171103
pubmed: 28671142
Galvagnion C, Brown JW, Ouberai MM, Flagmeier P, Vendruscolo M, Buell AK, et al. Chemical properties of lipids strongly affect the kinetics of the membrane-induced aggregation of α-synuclein. Proc Natl Acad Sci USA. 2016;113(26):7065–70. https://doi.org/10.1073/pnas.1601899113 .
doi: 10.1073/pnas.1601899113
pubmed: 27298346
pmcid: 4932957
Plotegher N, Berti G, Ferrari E, Tessari I, Zanetti M, Lunelli L, et al. DOPAL derived alpha-synuclein oligomers impair synaptic vesicles physiological function. Sci Rep. 2017;7:40699. https://doi.org/10.1038/srep40699 .
doi: 10.1038/srep40699
pubmed: 28084443
pmcid: 5233976
Limegrover CS, Yurko R, Izzo NJ, LaBarbera KM, Rehak C, Look G, et al. Sigma-2 receptor antagonists rescue neuronal dysfunction induced by Parkinson’s patient brain-derived α-synuclein. J Neurosci Res. 2021;99(4):1161–76. https://doi.org/10.1002/jnr.24782 .
doi: 10.1002/jnr.24782
pubmed: 33480104
pmcid: 7986605
Gold WA, Krishnarajy R, Ellaway C, Christodoulou J. Rett syndrome: a genetic update and clinical review focusing on comorbidities. ACS Chem Neurosci. 2018;9(2):167–76. https://doi.org/10.1021/acschemneuro.7b00346 .
doi: 10.1021/acschemneuro.7b00346
pubmed: 29185709
Vidal S, Xiol C, Pascual-Alonso A, O’Callaghan M, Pineda M, Armstrong J. Genetic landscape of Rett syndrome spectrum: improvements and challenges. Int J Mol Sci. 2019;20(16):3925. https://doi.org/10.3390/ijms20163925 .
doi: 10.3390/ijms20163925
pubmed: 31409060
pmcid: 6719047
Chahrour M, Jung SY, Shaw C, Zhou X, Wong ST, Qin J, et al. MeCP2, a key contributor to neurological disease, activates and represses transcription. Science. 2008;320(5880):1224–9. https://doi.org/10.1126/science.1153252 .
doi: 10.1126/science.1153252
pubmed: 18511691
pmcid: 2443785
Lyst MJ, Bird A. Rett syndrome: a complex disorder with simple roots. Nat Rev Genet. 2015;16(5):261–75. https://doi.org/10.1038/nrg3897 .
doi: 10.1038/nrg3897
pubmed: 25732612
Kriaucionis S, Paterson A, Curtis J, Guy J, Macleod N, Bird A. Gene expression analysis exposes mitochondrial abnormalities in a mouse model of Rett syndrome. Mol Cell Biol. 2006;26(13):5033–42. https://doi.org/10.1128/mcb.01665-05 .
doi: 10.1128/mcb.01665-05
pubmed: 16782889
pmcid: 1489175
Ricciardi S, Boggio EM, Grosso S, Lonetti G, Forlani G, Stefanelli G, et al. Reduced AKT/mTOR signaling and protein synthesis dysregulation in a Rett syndrome animal model. Hum Mol Genet. 2011;20(6):1182–96. https://doi.org/10.1093/hmg/ddq563 .
doi: 10.1093/hmg/ddq563
pubmed: 21212100
Palmer A, Qayumi J, Ronnett G. MeCP2 mutation causes distinguishable phases of acute and chronic defects in synaptogenesis and maintenance, respectively. Mol Cell Neurosci. 2008;37(4):794–807. https://doi.org/10.1016/j.mcn.2008.01.005 .
doi: 10.1016/j.mcn.2008.01.005
pubmed: 18295506
Fonzo M, Sirico F, Corrado B. Evidence-based physical therapy for individuals with Rett syndrome: a systematic review. Brain Sci. 2020;10(7):410. https://doi.org/10.3390/brainsci10070410 .
doi: 10.3390/brainsci10070410
pubmed: 32630125
pmcid: 7407501
Ehinger Y, Matagne V, Villard L, Roux JC. Rett syndrome from bench to bedside: recent advances. F1000Res. 2018;7:398. https://doi.org/10.12688/f1000research.14056.1 .
doi: 10.12688/f1000research.14056.1
pubmed: 29636907
pmcid: 5871944
Chahil G, Bollu PC. Rett Syndrome. In: Aboubakr S, Abu-Ghosh A, Acharya A, Adibi Sedeh P, Aeby T, Aeddula N, Et al. Editors. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. 2023. https://www.ncbi.nlm.nih.gov/books/NBK482252/ .
Ohno K, Saito Y, Ueda R, Togawa M, Ohmae T, Matsuda E, et al. Effect of serotonin 1A agonists and selective serotonin reuptake inhibitors on behavioral and nighttime respiratory symptoms in Rett syndrome. Pediatr Neurol. 2016;60:54-9.e1. https://doi.org/10.1016/j.pediatrneurol.2016.03.016 .
doi: 10.1016/j.pediatrneurol.2016.03.016
pubmed: 27212420
Neul JL, Lane JB, Lee H-S, Geerts S, Barrish JO, Annese F, et al. Developmental delay in Rett syndrome: data from the natural history study. J Neurodev Disord. 2014;6(1):20. https://doi.org/10.1186/1866-1955-6-20 .
doi: 10.1186/1866-1955-6-20
pubmed: 25071871
pmcid: 4112822
Luikenhuis S, Giacometti E, Beard CF, Jaenisch R. Expression of MeCP2 in postmitotic neurons rescues Rett syndrome in mice. Proc Natl Acad Sci USA. 2004;101(16):6033–8. https://doi.org/10.1073/pnas.0401626101 .
doi: 10.1073/pnas.0401626101
pubmed: 15069197
pmcid: 395918
Cohen DR, Matarazzo V, Palmer AM, Tu Y, Jeon O-H, Pevsner J, et al. Expression of MeCP2 in olfactory receptor neurons is developmentally regulated and occurs before synaptogenesis. Mol Cell Neurosci. 2003;22(4):417–29. https://doi.org/10.1016/s1044-7431(03)00026-5 .
doi: 10.1016/s1044-7431(03)00026-5
pubmed: 12727440
Chen WG, Chang Q, Lin Y, Meissner A, West AE, Griffith EC, et al. Derepression of BDNF transcription involves calcium-dependent phosphorylation of MeCP2. Science. 2003;302(5646):885–9. https://doi.org/10.1126/science.1086446 .
doi: 10.1126/science.1086446
pubmed: 14593183
Kikuchi-Utsumi K, Nakaki T. Chronic treatment with a selective ligand for the sigma-1 receptor chaperone, SA4503, up-regulates BDNF protein levels in the rat hippocampus. Neurosci Lett. 2008;440(1):19–22. https://doi.org/10.1016/j.neulet.2008.05.055 .
doi: 10.1016/j.neulet.2008.05.055
pubmed: 18547721
Mysona BA, Zhao J, Smith S, Bollinger KE. Relationship between Sigma-1 receptor and BDNF in the visual system. Exp Eye Res. 2018;167:25–30. https://doi.org/10.1016/j.exer.2017.10.012 .
doi: 10.1016/j.exer.2017.10.012
pubmed: 29031856
Hashimoto K. Sigma-1 receptor chaperone and brain-derived neurotrophic factor: emerging links between cardiovascular disease and depression. Prog Neurobiol. 2013;100:15–29. https://doi.org/10.1016/j.pneurobio.2012.09.001 .
doi: 10.1016/j.pneurobio.2012.09.001
pubmed: 23044468
Nakano M, Osada K, Misonoo A, Fujiwara K, Takahashi M, Ogawa Y, et al. Fluvoxamine and sigma-1 receptor agonists dehydroepiandrosterone (DHEA)-sulfate induces the Ser473-phosphorylation of Akt-1 in PC12 cells. Life Sci. 2010;86(9–10):309–14. https://doi.org/10.1016/j.lfs.2009.11.017 .
doi: 10.1016/j.lfs.2009.11.017
pubmed: 19995565
Christ MG, Clement AM, Behl C. The sigma-1 receptor at the crossroad of proteostasis, neurodegeneration, and autophagy. Trends Neurosci. 2020;43(2):79–81. https://doi.org/10.1016/j.tins.2019.12.002 .
doi: 10.1016/j.tins.2019.12.002
pubmed: 31918966
Urano F. Wolfram syndrome: diagnosis, management, and treatment. Curr Diab Rep. 2016;16(1):6. https://doi.org/10.1007/s11892-015-0702-6 .
doi: 10.1007/s11892-015-0702-6
pubmed: 26742931
pmcid: 4705145
Abreu D, Urano F. Current landscape of treatments for Wolfram syndrome. Trends Pharmacol Sci. 2019;40(10):711–4. https://doi.org/10.1016/j.tips.2019.07.011 .
doi: 10.1016/j.tips.2019.07.011
pubmed: 31420094
pmcid: 7547529
Delprat B, Maurice T, Delettre C. Wolfram syndrome: MAMs’ connection? Cell Death Dis. 2018;9(3):364. https://doi.org/10.1038/s41419-018-0406-3 .
doi: 10.1038/s41419-018-0406-3
pubmed: 29511163
pmcid: 5840383
Mori T, Hayashi T, Hayashi E, Su TP. Sigma-1 receptor chaperone at the ER-mitochondrion interface mediates the mitochondrion-ER-nucleus signaling for cellular survival. PLoS ONE. 2013;8(10):e76941. https://doi.org/10.1371/journal.pone.0076941 .
doi: 10.1371/journal.pone.0076941
pubmed: 24204710
pmcid: 3799859
Crouzier L, Danese A, Yasui Y, Richard EM, Liévens J-C, Patergnani S, et al. Activation of the sigma-1 receptor chaperone alleviates symptoms of Wolfram syndrome in preclinical models. Sci Transl Med. 2022;14(631):eabh3763. https://doi.org/10.1126/scitranslmed.abh3763 .
doi: 10.1126/scitranslmed.abh3763
pubmed: 35138910
pmcid: 9516885
Kornhuber J, Bormann J, Hübers M, Rusche K, Riederer P. Effects of the 1-amino-adamantanes at the MK-801-binding site of the NMDA-receptor-gated ion channel: a human postmortem brain study. Eur J Pharmacol. 1991;206(4):297–300. https://doi.org/10.1016/0922-4106(91)90113-v .
doi: 10.1016/0922-4106(91)90113-v
pubmed: 1717296
Blanpied TA, Clarke RJ, Johnson JW. Amantadine inhibits NMDA receptors by accelerating channel closure during channel block. J Neurosci. 2005;25(13):3312–22. https://doi.org/10.1523/jneurosci.4262-04.2005 .
doi: 10.1523/jneurosci.4262-04.2005
pubmed: 15800186
pmcid: 6724906
Peeters M, Romieu P, Maurice T, Su TP, Maloteaux JM, Hermans E. Involvement of the sigma1 receptor in the modulation of dopaminergic transmission by amantadine. Eur J Neurosci. 2004;19(8):2212–20. https://doi.org/10.1111/j.0953-816X.2004.03297.x .
doi: 10.1111/j.0953-816X.2004.03297.x
pubmed: 15090047
Abbas H. Expression of sigma receptors in human cancer cell lines and effects of novel sigma-2 ligands on their proliferation [Doctoral Thesis]. In. The University of Wolverhampton open repository. 2018. http://hdl.handle.net/2436/621768 . Accessed 1 Dec 2022.
Hubsher G, Haider M, Okun MS. Amantadine: the journey from fighting flu to treating Parkinson disease. Neurology. 2012;78(14):1096–9. https://doi.org/10.1212/WNL.0b013e31824e8f0d .
doi: 10.1212/WNL.0b013e31824e8f0d
pubmed: 22474298
Chang C, Ramphul K. Amantadine. In: Aboubakr S, Abu-Ghosh A, Acharya A, Adibi Sedeh P, Aeby T, Aeddula N, et al. Editors. StatPearls. Treasure Island (FL): StatPearls Publishing. 2023. https://www.ncbi.nlm.nih.gov/books/NBK499953/ .
Schwab RS, England AC, Poskanzer DC, Young RR. Amantadine in the treatment of Parkinson’s disease. JAMA. 1969;208(7):1168–70.
doi: 10.1001/jama.1969.03160070046011
pubmed: 5818715
Rascol O, Fabbri M, Poewe W. Amantadine in the treatment of Parkinson’s disease and other movement disorders. Lancet Neurol. 2021;20(12):1048–56. https://doi.org/10.1016/S1474-4422(21)00249-0 .
doi: 10.1016/S1474-4422(21)00249-0
pubmed: 34678171
Kornhuber J, Schoppmeyer K, Riederer P. Affinity of 1-aminoadamantanes for the σ binding site in post-mortem human frontal cortex. Neurosci Lett. 1993;163(2):129–31. https://doi.org/10.1016/0304-3940(93)90362-O .
doi: 10.1016/0304-3940(93)90362-O
pubmed: 8309617
Crosby NJ, Deane KH, Clarke CE. Amantadine for dyskinesia in Parkinson’s disease. Cochrane Database Syst Rev. 2003;2003(2):CD003467. https://doi.org/10.1002/14651858.Cd003467 .
doi: 10.1002/14651858.Cd003467
pubmed: 12804468
pmcid: 8715285
Aoki FY, Sitar DS. Clinical pharmacokinetics of amantadine hydrochloride. Clin Pharmacokinet. 1988;14(1):35–51. https://doi.org/10.2165/00003088-198814010-00003 .
doi: 10.2165/00003088-198814010-00003
pubmed: 3280212
Al-Salama ZT. Amantadine extended release capsules (GOCOVRI) in Parkinson’s disease: a profile of its use in the USA. Drugs Ther Perspect. 2022;38(5):203–14. https://doi.org/10.1007/s40267-022-00912-y .
doi: 10.1007/s40267-022-00912-y
Hauser RA, Mehta SH, Kremens D, et al. Effects of Gocovri (amantadine) extended-release capsules on motor aspects of experiences of daily living in people with Parkinson’s disease and dyskinesia. Neurol Ther. 2021;10(2):739–51. https://doi.org/10.1007/s40120-021-00256-1 .
doi: 10.1007/s40120-021-00256-1
pubmed: 34024025
pmcid: 8571461
Elmer LW, Juncos JL, Singer C, et al. Pooled analyses of phase III studies of ADS-5102 (amantadine) extended-release capsules for dyskinesia in Parkinson’s disease. CNS Drugs. 2018;32:387–98. https://doi.org/10.1007/s40263-018-0498-4 .
doi: 10.1007/s40263-018-0498-4
pubmed: 29532440
pmcid: 5934466
Isaacson SH, Fahn S, Pahwa R, et al. Parkinson’s patients with dyskinesia switched from immediate release amantadine to open-label ADS-5102. Mov Disord Clin Pract. 2018;5:183–90. https://doi.org/10.1002/mdc3.12595 .
doi: 10.1002/mdc3.12595
pubmed: 29780852
pmcid: 5947645
Oertel W, Eggert K, Pahwa R, Tanner CM, Hauser RA, Trenkwalder C, et al. Randomized, placebo-controlled trial of ADS-5102 (amantadine) extended-release capsules for levodopa-induced dyskinesia in Parkinson’s disease (EASE LID 3). Mov Disord. 2017;32(12):1701–9. https://doi.org/10.1002/mds.27131 .
doi: 10.1002/mds.27131
pubmed: 28833562
pmcid: 5763269
Pahwa R, Tanner CM, Hauser RA, Isaacson SH, Nausieda PA, Truong DD, et al. ADS-5102 (amantadine) extended-release capsules for levodopa-induced dyskinesia in Parkinson disease (EASE LID study): a randomized clinical trial. JAMA Neurol. 2017;74(8):941–9. https://doi.org/10.1001/jamaneurol.2017.0943 .
doi: 10.1001/jamaneurol.2017.0943
pubmed: 28604926
pmcid: 5710325
Tanner CM, Pahwa R, Hauser RA, Oertel WH, Isaacson SH, Jankovic J, et al. EASE LID 2: a 2-year open-label trial of gocovri (amantadine) extended release for dyskinesia in Parkinson’s disease. J Parkinsons Dis. 2020;10(2):543–58. https://doi.org/10.3233/JPD-191841 .
doi: 10.3233/JPD-191841
pubmed: 31929122
pmcid: 7242830
Rosenberg GA, Appenzeller O. Amantadine, fatigue, and multiple sclerosis. Arch Neurol. 1988;45(10):1104–6. https://doi.org/10.1001/archneur.1988.00520340058012 .
doi: 10.1001/archneur.1988.00520340058012
pubmed: 2972270
Shaygannejad V, Janghorbani M, Ashtari F, Zakeri H. Comparison of the effect of aspirin and amantadine for the treatment of fatigue in multiple sclerosis: a randomized, blinded, crossover study. Neurol Res. 2012;34(9):854–8. https://doi.org/10.1179/1743132812Y.0000000081 .
doi: 10.1179/1743132812Y.0000000081
pubmed: 22979982
Ledinek AH, Sajko MC, Rot U. Evaluating the effects of amantadin, modafinil and acetyl-L-carnitine on fatigue in multiple sclerosis–result of a pilot randomized, blind study. Clin Neurol Neurosurg. 2013;115:S86–9. https://doi.org/10.1016/j.clineuro.2013.09.029 .
doi: 10.1016/j.clineuro.2013.09.029
pubmed: 24321164
Khazaei M, Karevan A, Taheri M, Ghafouri-Fard S. Comparison of the effects of amantadine and ondansetron in treatment of fatigue in patients with multiple sclerosis. Clin Transl Med. 2019;8(1):20. https://doi.org/10.1186/s40169-019-0239-4 .
doi: 10.1186/s40169-019-0239-4
pubmed: 31263986
pmcid: 6603072
Puca F, Bricolo A, Turella G. Effect of L-dopa or amantadine therapy on sleep spindles in Parkinsonism. Electroencephalogr Clin Neurophysiol. 1973;35(3):327–30. https://doi.org/10.1016/0013-4694(73)90245-9 .
doi: 10.1016/0013-4694(73)90245-9
pubmed: 4126184
Nourbakhsh B, Revirajan N, Morris B, Cordano C, Creasman J, Manguinao M, et al. Safety and efficacy of amantadine, modafinil, and methylphenidate for fatigue in multiple sclerosis: a randomised, placebo-controlled, crossover, double-blind trial. Lancet Neurol. 2021;20(1):38–48. https://doi.org/10.1016/s1474-4422(20)30354-9 .
doi: 10.1016/s1474-4422(20)30354-9
pubmed: 33242419
Villard V, Espallergues J, Keller E, Vamvakides A, Maurice T. Anti-amnesic and neuroprotective potentials of the mixed muscarinic receptor/sigma1 (σ1) ligand ANAVEX2-73, a novel aminotetrahydrofuran derivative. J Psychopharmacol. 2011;25(8):1101–17. https://doi.org/10.1177/0269881110379286 .
doi: 10.1177/0269881110379286
pubmed: 20829307
Lahmy V, Meunier J, Malmström S, Naert G, Givalois L, Kim SH, et al. Blockade of Tau hyperphosphorylation and Aβ 1–42 generation by the aminotetrahydrofuran derivative ANAVEX2-73, a mixed muscarinic and σ 1 receptor agonist, in a nontransgenic mouse model of Alzheimer’s disease. Neuropsychopharmacology. 2013;38(9):1706. https://doi.org/10.1038/npp.2013.70 .
doi: 10.1038/npp.2013.70
pubmed: 23493042
pmcid: 3717544
Lahmy V, Long R, Morin D, Villard V, Maurice T. Mitochondrial protection by the mixed muscarinic/σ1 ligand ANAVEX2-73, a tetrahydrofuran derivative, in Aβ25–35 peptide-injected mice, a nontransgenic Alzheimer’s disease model. Front Cell Neurosci. 2015;8:463. https://doi.org/10.3389/fncel.2014.00463 .
doi: 10.3389/fncel.2014.00463
pubmed: 25653589
pmcid: 4299448
Voges O, Weigmann I, Bitterlich N, Missling C, Schindler C. A Phase I dose escalation study to investigate safety, tolerability, and pharmacokinetics of ANAVEX 2‐73 in Healthy Male Subjects. Innov Clin Neurosci. 2014;12(Suppl B), 1-20; CNS Summit 2014, Boca Raton, Florida.
Hampel H, Williams C, Etcheto A, Goodsaid F, Parmentier F, Sallantin J, et al. A precision medicine framework using artificial intelligence for the identification and confirmation of genomic biomarkers of response to an Alzheimer’s disease therapy: Analysis of the blarcamesine (ANAVEX2-73) Phase 2a clinical study. Alzheimers Dement. 2020;6(1):e12013. https://doi.org/10.1002/trc2.12013 .
doi: 10.1002/trc2.12013
Lisak RP, Nedelkoska L, Benjamins JA. Sigma-1 receptor agonists as potential protective therapies in multiple sclerosis. J Neuroimmunol. 2020;342:577188. https://doi.org/10.1016/j.jneuroim.2020.577188 .
doi: 10.1016/j.jneuroim.2020.577188
pubmed: 32179326
Kaufmann WE, Sprouse J, Rebowe N, Hanania T, Klamer D, Missling CU. ANAVEX 2–73 (blarcamesine), a Sigma-1 receptor agonist, ameliorates neurologic impairments in a mouse model of Rett syndrome. Pharmacol Biochem Behav. 2019;187:172796. https://doi.org/10.1016/j.pbb.2019.172796 .
doi: 10.1016/j.pbb.2019.172796
pubmed: 31704481
Reyes ST, Deacon RM, Guo SG, Altimiras FJ, Castillo JB, van der Wildt B, et al. Effects of the sigma-1 receptor agonist blarcamesine in a murine model of fragile X syndrome: neurobehavioral phenotypes and receptor occupancy. Sci Rep. 2021;11(1):17150. https://doi.org/10.1038/s41598-021-94079-7 .
doi: 10.1038/s41598-021-94079-7
pubmed: 34433831
pmcid: 8387417
Anavex-Life-Sciences-Corp. ANAVEX2-73 (Blarcamesine) AVATAR phase 3 trial met primary and secondary efficacy endpoints. In: Anavex press release. 2022. https://www.anavex.com/post/anavex-2-73-blarcamesine-avatar-phase-3-trial-met-primary-and-secondary-efficacy-endpoints . Accessed 1 Nov 2022.
Hall H, Iulita MF, Gubert P, Flores Aguilar L, Ducatenzeiler A, Fisher A, et al. AF710B, an M1/sigma-1 receptor agonist with long-lasting disease-modifying properties in a transgenic rat model of Alzheimer’s disease. Alzheimers Dement. 2018;14(6):811–23. https://doi.org/10.1016/j.jalz.2017.11.009 .
doi: 10.1016/j.jalz.2017.11.009
pubmed: 29291374
Anavex-life-Sciences-Corp. Anavex Life Sciences reports positive results from phase 1 clinical trial of ANAVEX3-71. In: Anavex press release. 2022. https://www.anavex.com/post/anavex-life-sciences-reports-positive-results-from-phase-1-clinical-trial-of-anavex-3-71 . Accessed 1 Nov 2022.
Rishton GM, Look GC, Ni ZJ, Zhang J, Wang Y, Huang Y, et al. Discovery of investigational drug CT1812, an antagonist of the Sigma-2 receptor complex for Alzheimer’s disease. ACS Med Chem Lett. 2021;12(9):1389–95. https://doi.org/10.1021/acsmedchemlett.1c00048 .
doi: 10.1021/acsmedchemlett.1c00048
pubmed: 34531947
pmcid: 8436239
Izzo NJ, Xu J, Zeng C, Kirk MJ, Mozzoni K, Silky C, et al. Alzheimer’s therapeutics targeting amyloid beta 1–42 oligomers II: sigma-2/PGRMC1 receptors mediate Abeta 42 oligomer binding and synaptotoxicity. PLoS ONE. 2014;9(11):e111899. https://doi.org/10.1371/journal.pone.0111899 .
doi: 10.1371/journal.pone.0111899
pubmed: 25390692
pmcid: 4229119
Izzo NJ, Yuede CM, LaBarbera KM, Limegrover CS, Rehak C, Yurko R, et al. Preclinical and clinical biomarker studies of CT1812: a novel approach to Alzheimer’s disease modification. Alzheimers Dement. 2021;17(8):1365–82. https://doi.org/10.1371/journal.pone.0111899 .
doi: 10.1371/journal.pone.0111899
pubmed: 33559354
pmcid: 8349378
Harper AR, Nayee S, Topol EJ. Protective alleles and modifier variants in human health and disease. Nat Rev Genet. 2015;16(12):689–701. https://doi.org/10.1038/nrg4017 .
doi: 10.1038/nrg4017
pubmed: 26503796
Grundman M, Morgan R, Lickliter JD, Schneider LS, DeKosky S, Izzo NJ, et al. A phase 1 clinical trial of the sigma-2 receptor complex allosteric antagonist CT1812, a novel therapeutic candidate for Alzheimer’s disease. Alzheimers Dement. 2019;5:20–6. https://doi.org/10.1016/j.trci.2018.11.001 .
doi: 10.1016/j.trci.2018.11.001
Catalano S, Grundman M, Schneider LS, DeKosky S, Morgan R, Guttendorf R, et al. [P4–567]: a phase 1 safety trial of the Aβ oligomer receptor antagonist CT1812. Alzheimers Dement. 2017;13(7S):P1523–80. https://doi.org/10.1016/j.jalz.2017.07.730 .
doi: 10.1016/j.jalz.2017.07.730
Schwartz AR, Pizon AF, Brooks DE. Dextromethorphan-induced serotonin syndrome. Clin Toxicol. 2008;46(8):771–3. https://doi.org/10.1080/15563650701668625 .
doi: 10.1080/15563650701668625
Shin EJ, Nah SY, Chae JS, Bing G, Shin SW, Yen TP, et al. Dextromethorphan attenuates trimethyltin-induced neurotoxicity via sigma1 receptor activation in rats. Neurochem Int. 2007;50(6):791–9. https://doi.org/10.1016/j.neuint.2007.01.008 .
doi: 10.1016/j.neuint.2007.01.008
pubmed: 17386960
Nguyen L, Thomas KL, Lucke-Wold BP, Cavendish JZ, Crowe MS, Matsumoto RR. Dextromethorphan: an update on its utility for neurological and neuropsychiatric disorders. Pharmacol Ther. 2016;159:1–22. https://doi.org/10.1016/j.pharmthera.2016.01.016 .
doi: 10.1016/j.pharmthera.2016.01.016
pubmed: 26826604
Sauvé WM. Recognizing and treating pseudobulbar affect. CNS Spectr. 2016;21(S1):34–44. https://doi.org/10.1017/S1092852916000791 .
doi: 10.1017/S1092852916000791
pubmed: 28044945
Garnock-Jones KP. Dextromethorphan/quinidine. CNS Drugs. 2011;25(5):435–45. https://doi.org/10.2165/11207260-000000000-00000 .
doi: 10.2165/11207260-000000000-00000
pubmed: 21476614
Cummings JL, Lyketsos CG, Peskind ER, Porsteinsson AP, Mintzer JE, Scharre DW, et al. Effect of dextromethorphan-quinidine on agitation in patients with Alzheimer disease dementia: a randomized clinical trial. JAMA. 2015;314(12):1242–54. https://doi.org/10.1001/jama.2015.10214 .
doi: 10.1001/jama.2015.10214
pubmed: 26393847
Senanarong V, Cummings J, Fairbanks L, Mega M, Masterman D, O’connor S, et al. Agitation in Alzheimer’s disease is a manifestation of frontal lobe dysfunction. Dement Geriatr Cogn Disord. 2004;17(1–2):14–20. https://doi.org/10.1159/000074080 .
doi: 10.1159/000074080
pubmed: 14560060
O’Gorman C, Jones A, Cummings JL, et al. Efficacy and safety of AXS‐05, a novel, oral, NMDA‐receptor antagonist with multimodal activity, in agitation associated with Alzheimer’s disease: results from ADVANCE‐1, a phase 2/3, double‐blind, active and placebo‐controlled trial: developments in clinical trials and cognitive assessment. Alzheimer Dement. 2020;16:e047684. https://doi.org/10.1002/alz.047684 .
doi: 10.1002/alz.047684
Chou Y-C, Liao J-F, Chang W-Y, Lin M-F, Chen C-F. Binding of dimemorfan to sigma-1 receptor and its anticonvulsant and locomotor effects in mice, compared with dextromethorphan and dextrorphan. Brain Res. 1999;821(2):516–9. https://doi.org/10.1016/s0006-8993(99)01125-7 .
doi: 10.1016/s0006-8993(99)01125-7
pubmed: 10064839
Verhagen Metman L, Del Dotto P, Natté R, van den Munckhof P, Chase TN. Dextromethorphan improves levodopa-induced dyskinesias in Parkinson’s disease. Neurology. 1998;51(1):203–6. https://doi.org/10.1212/wnl.51.1.203 .
doi: 10.1212/wnl.51.1.203
pubmed: 9674803
Starr MS, Starr BS, Kaur S. Stimulation of basal and L-DOPA-induced motor activity by glutamate antagonists in animal models of Parkinson’s disease. Neurosci Biobehav Rev. 1997;21(4):437–46. https://doi.org/10.1016/s0149-7634(96)00039-5 .
doi: 10.1016/s0149-7634(96)00039-5
pubmed: 9195601
Paquette MA, Brudney EG, Putterman DB, Meshul CK, Johnson SW, Berger SP. Sigma ligands, but not N-methyl-D-aspartate antagonists, reduce levodopa-induced dyskinesias. NeuroReport. 2008;19(1):111–5. https://doi.org/10.1097/WNR.0b013e3282f3b0d1 .
doi: 10.1097/WNR.0b013e3282f3b0d1
pubmed: 18281903
pmcid: 2845294
Liu C-T, Kao L-T, Shih J-H, Chien W-C, Chiu C-H, Ma K-H, et al. The effect of dextromethorphan use in Parkinson’s disease: a 6-hydroxydopamine rat model and population-based study. Eur J Pharmacol. 2019;862:172639. https://doi.org/10.1016/j.ejphar.2019.172639 .
doi: 10.1016/j.ejphar.2019.172639
pubmed: 31491406
Fox SH, Metman LV, Nutt JG, Brodsky M, Factor SA, Lang AE, et al. Trial of dextromethorphan/quinidine to treat levodopa-induced dyskinesia in Parkinson’s disease. Mov Disord. 2017;32(6):893–903. https://doi.org/10.1002/mds.26976 .
doi: 10.1002/mds.26976
pubmed: 28370447
Verhagen Metman L, Blanchet PJ, van den Munckhof P, Del Dotto P, Natté R, Chase TN. A trial of dextromethorphan in parkinsonian patients with motor response complications. Mov Disord. 1998;13(3):414–7. https://doi.org/10.1002/mds.870130307 .
doi: 10.1002/mds.870130307
pubmed: 9613730
Wilhelm R, Ahl B, Anghelescu I-G. Dextrometorphan-paroxetine, but not dronabinol, effective for treatment-resistant aggression and agitation in an elderly patient with Lewy body dementia. J Clin Psychopharmacol. 2017;37(6):745–7. https://doi.org/10.1097/jcp.0000000000000805 .
doi: 10.1097/jcp.0000000000000805
pubmed: 29035934
Logan BK, Yeakel JK, Goldfogel G, Frost MP, Sandstrom G, Wickham DJ. Dextromethorphan abuse leading to assault, suicide, or homicide. J Forensic Sci. 2012;57(5):1388–94. https://doi.org/10.1111/j.1556-4029.2012.02133.x .
doi: 10.1111/j.1556-4029.2012.02133.x
pubmed: 22537430
Smith R, Pioro E, Myers K, Sirdofsky M, Goslin K, Meekins G, et al. Enhanced bulbar function in amyotrophic lateral sclerosis: the Nuedexta treatment trial. Neurotherapeutics. 2017;14(3):762–72. https://doi.org/10.1007/s13311-016-0508-5 .
doi: 10.1007/s13311-016-0508-5
pubmed: 28070747
pmcid: 5509619
Green JR, Allison KM, Cordella C, Richburg BD, Pattee GL, Berry JD, et al. Additional evidence for a therapeutic effect of dextromethorphan/quinidine on bulbar motor function in patients with amyotrophic lateral sclerosis: a quantitative speech analysis. Br J Clin Pharmacol. 2018;84(12):2849–56. https://doi.org/10.1111/bcp.13745 .
doi: 10.1111/bcp.13745
pubmed: 30152872
pmcid: 6256051
Sancho J, Ferrer S, Burés E, Díaz JL, Torrecilla T, Signes-Costa J, et al. Effect of one-year dextromethorphan/quinidine treatment on management of respiratory impairment in amyotrophic lateral sclerosis. Respir Med. 2021;186:106536. https://doi.org/10.1016/j.rmed.2021.106536 .
doi: 10.1016/j.rmed.2021.106536
pubmed: 34260979
Chechneva OV, Mayrhofer F, Daugherty DJ, Pleasure DE, Hong J-S, Deng W. Low dose dextromethorphan attenuates moderate experimental autoimmune encephalomyelitis by inhibiting NOX2 and reducing peripheral immune cells infiltration in the spinal cord. Neurobiol Dis. 2011;44(1):63–72. https://doi.org/10.1016/j.nbd.2011.06.004 .
doi: 10.1016/j.nbd.2011.06.004
pubmed: 21704706
pmcid: 3153572
Lisak RP, Nedelkoska L, Benjamins JA. Effects of dextromethorphan on glial cell function: proliferation, maturation, and protection from cytotoxic molecules. Glia. 2014;62(5):751–62. https://doi.org/10.1002/glia.22639 .
doi: 10.1002/glia.22639
pubmed: 24526455
Pioro EP, Brooks BR, Cummings J, Schiffer R, Thisted RA, Wynn D, et al. Dextromethorphan plus ultra low-dose quinidine reduces pseudobulbar affect. Ann Neurol. 2010;68(5):693–702. https://doi.org/10.1002/ana.22093 .
doi: 10.1002/ana.22093
pubmed: 20839238
McGrane I, VandenBerg A, Munjal R. Treatment of pseudobulbar affect with fluoxetine and dextromethorphan in a woman with multiple sclerosis. Ann Pharmacother. 2017;51(11):1035–6. https://doi.org/10.1177/1060028017720746 .
doi: 10.1177/1060028017720746
pubmed: 28691510
Ehde DM, Osborne TL, Jensen MP. Chronic pain in persons with multiple sclerosis. Phys Med Rehabil Clin N Am. 2005;16(2):503–12. https://doi.org/10.1016/j.pmr.2005.01.001 .
doi: 10.1016/j.pmr.2005.01.001
pubmed: 15893684
Merlos M, Romero L, Zamanillo D, Plata-Salamán C, Vela JM. Sigma-1 receptor and pain. Handb Exp Pharmacol. 2017;244:131–61. https://doi.org/10.1007/164_2017_9 .
doi: 10.1007/164_2017_9
pubmed: 28275913
Panitch HS, Thisted RA, Smith RA, Wynn DR, Wymer JP, Achiron A, et al. Randomized, controlled trial of dextromethorphan/quinidine for pseudobulbar affect in multiple sclerosis. Ann Neurol. 2006;59(5):780–7. https://doi.org/10.1002/ana.20828 .
doi: 10.1002/ana.20828
pubmed: 16634036
Nelson KA, Park KM, Robinovitz E, Tsigos C, Max MB. High-dose oral dextromethorphan versus placebo in painful diabetic neuropathy and postherpetic neuralgia. Neurology. 1997;48(5):1212–8. https://doi.org/10.1212/wnl.48.5.1212 .
doi: 10.1212/wnl.48.5.1212
pubmed: 9153445
Abraham RB, Marouani N, Kollender Y, Meller I, Weinbroum AA. Dextromethorphan for phantom pain attenuation in cancer amputees: a double-blind crossover trial involving three patients. Clin J Pain. 2002;18(5):282–5. https://doi.org/10.1097/00002508-200209000-00002 .
doi: 10.1097/00002508-200209000-00002
pubmed: 12218498
Carlsson K, Hoem N, Moberg E, Mathisen L. Analgesic effect of dextromethorphan in neuropathic pain. Acta Anaesthesiol Scand. 2004;48(3):328–36. https://doi.org/10.1111/j.0001-5172.2004.0325.x .
doi: 10.1111/j.0001-5172.2004.0325.x
pubmed: 14982566
Gilron I, Booher S, Rowan J, Smoller B, Max M. A randomized, controlled trial of high-dose dextromethorphan in facial neuralgias. Neurology. 2000;55(7):964–71. https://doi.org/10.1212/wnl.55.7.964 .
doi: 10.1212/wnl.55.7.964
pubmed: 11061252
McQuay HJ, Carroll D, Jadad AR, Glynn CJ, Jack T, Moore RA, et al. Dextromethorphan for the treatment of neuropathic pain: a double-blind randomised controlled crossover trial with integral n-of-1 design. Pain. 1994;59(1):127–33. https://doi.org/10.1016/0304-3959(94)90056-6 .
doi: 10.1016/0304-3959(94)90056-6
pubmed: 7854793
Smith-Hicks CL, Gupta S, Ewen JB, Hong M, Kratz L, Kelley R, Tierney E, Vaurio R, Bibat G, Sanyal A, Yenokyan G, Brereton N, Johnston MV, Naidu S. Randomized open-label trial of dextromethorphan in Rett syndrome. Neurology. 2017;89(16):1684–90. https://doi.org/10.1212/WNL.0000000000004515 .
doi: 10.1212/WNL.0000000000004515
pubmed: 28931647
pmcid: 5644464
Kumagai K, Shono K, Nakayama H, Ohno Y, Sajai I. (2R-trans)-2-butyl-5-heptylpyrrolidine as a potent sigma receptor ligand produced by Streptomyces longispororuber. Journal Antibiot. 2000;53(5):467–73. https://doi.org/10.7164/antibiotics.53.467 .
doi: 10.7164/antibiotics.53.467
Moebius FF, Reiter RJ, Hanner M, Glossmann H. High affinity of sigma1-binding sites for sterol isomerization inhibitors: evidence for a pharmacological relationship with the yeast sterol C8–C7 isomerase. Br J Pharmacol. 1997;121(1):1–6. https://doi.org/10.1038/sj.bjp.0701079 .
doi: 10.1038/sj.bjp.0701079
pubmed: 9146879
pmcid: 1564641
Ramachandran S, Chu UB, Mavlyutov TA, Pal A, Pyne S, Ruoho AE. The sigma1 receptor interacts with N-alkyl amines and endogenous sphingolipids. Eur J Pharmacol. 2009;609(1–3):19–26. https://doi.org/10.1016/j.ejphar.2009.03.003 .
doi: 10.1016/j.ejphar.2009.03.003
pubmed: 19285059
pmcid: 3194046
Li J, Satyshur K, Guo LW, Ruoho AE. Sphingoid bases regulate the Sigma-1 receptor—sphingosine and N,N’-dimethylsphingosine are endogenous agonists. Int J Mol Sci. 24(4):3103; Doi: https://doi.org/10.3390/ijms24043103
National-Institute-for-Health-and-Care-Excellence. Donepezil, galantamine, rivastigmine and memantine for the treatment of Alzheimer’s disease. In: National Institute for Heath Care Excelence. 2011;TA217:1-77; https://www.nice.org.uk/guidance/ta217 . Accessed 1 Nov 2022.
Kato K, Hayako H, Ishihara Y, Marui S, Iwane M, Miyamoto M. TAK-147, an acetylcholinesterase inhibitor, increases choline acetyltransferase activity in cultured rat septal cholinergic neurons. Neurosci Lett. 1999;260(1):5–8. https://doi.org/10.1016/S0304-3940(98)00943-4 .
doi: 10.1016/S0304-3940(98)00943-4
pubmed: 10027686
Ramakrishnan NK, Visser AK, Schepers M, Luurtsema G, Nyakas CJ, Elsinga PH, et al. Dose-dependent sigma-1 receptor occupancy by donepezil in rat brain can be assessed with 11 C-SA4503 and microPET. Psychopharmacology. 2014;231(20):3997–4006. https://doi.org/10.1007/s00213-014-3533-2 .
doi: 10.1007/s00213-014-3533-2
pubmed: 24639047
Sato K, Urbano R, Yu C, Yamasaki F, Sato T, Jordan J, et al. The effect of donepezil treatment on cardiovascular mortality. Clin Pharmacol Ther. 2010;88(3):335–8. https://doi.org/10.1038/clpt.2010.98 .
doi: 10.1038/clpt.2010.98
pubmed: 20664535
Nordström P, Religa D, Wimo A, Winblad B, Eriksdotter M. The use of cholinesterase inhibitors and the risk of myocardial infarction and death: a nationwide cohort study in subjects with Alzheimer’s disease. Eur Heart J. 2013;34(33):2585–91. https://doi.org/10.1093/eurheartj/eht182 .
doi: 10.1093/eurheartj/eht182
pubmed: 23735859
Bhuiyan MS, Fukunaga K. Targeting sigma-1 receptor signaling by endogenous ligands for cardioprotection. Expert Opin Ther Targets. 2011;15(2):145–55. https://doi.org/10.1517/14728222.2011.546350 .
doi: 10.1517/14728222.2011.546350
pubmed: 21204730
Ishima T, Nishimura T, Iyo M, Hashimoto K. Potentiation of nerve growth factor-induced neurite outgrowth in PC12 cells by donepezil: role of sigma-1 receptors and IP3 receptors. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32(7):1656–9. https://doi.org/10.1016/j.pnpbp.2008.06.011 .
doi: 10.1016/j.pnpbp.2008.06.011
pubmed: 18647636
Zhang X, Lian S, Zhang Y, Zhao Q. Efficacy and safety of donepezil for mild cognitive impairment: a systematic review and meta-analysis. Clin Neurol Neurosurg. 2022;213:107134. https://doi.org/10.1016/j.clineuro.2022.107134 .
doi: 10.1016/j.clineuro.2022.107134
pubmed: 35078087
Birks JS, Harvey RJ. Donepezil for dementia due to Alzheimer’s disease. Cochrane Database Syst Rev. 2018;6(6):CD001190. https://doi.org/10.1002/14651858.CD001190.pub3 .
doi: 10.1002/14651858.CD001190.pub3
pubmed: 29923184
Wang H, Zong Y, Han Y, Zhao J, Liu H, Liu Y. Compared of efficacy and safety of high-dose donepezil vs standard-dose donepezil among elderly patients with Alzheimer’s disease: a systematic review and meta-analysis. Expert Opin Drug Saf. 2022;21(3):407–15. https://doi.org/10.1080/14740338.2022.2027905 .
doi: 10.1080/14740338.2022.2027905
pubmed: 35099343
Howard R, McShane R, Lindesay J, Ritchie C, Baldwin A, Barber R, et al. Donepezil and memantine for moderate-to-severe Alzheimer’s disease. N Engl J Med. 2012;366(10):893–903. https://doi.org/10.1056/NEJMoa1106668 .
doi: 10.1056/NEJMoa1106668
pubmed: 22397651
Tariot PN, Cummings JL, Katz IR, Mintzer J, Perdomo CA, Schwam EM, et al. A randomized, double-blind, placebo-controlled study of the efficacy and safety of donepezil in patients with Alzheimer’s disease in the nursing home setting. J Am Geriatr Soc. 2001;49(12):1590–9.
doi: 10.1111/j.1532-5415.2001.49266.x
pubmed: 11843990
Ye CY, Lei Y, Tang XC, Zhang HY. Donepezil attenuates Aβ-associated mitochondrial dysfunction and reduces mitochondrial Aβ accumulation in vivo and in vitro. Neuropharmacology. 2015;95:29–36. https://doi.org/10.1016/j.neuropharm.2015.02.020 .
doi: 10.1016/j.neuropharm.2015.02.020
pubmed: 25744714
Dong H, Yuede CM, Coughlan CA, Murphy KM, Csernansky JG. Effects of donepezil on amyloid-β and synapse density in the Tg2576 mouse model of Alzheimer’s disease. Brain Res. 2009;1303:169–78. https://doi.org/10.1016/j.brainres.2009.09.097 .
doi: 10.1016/j.brainres.2009.09.097
pubmed: 19799879
pmcid: 2789417
Ishibashi K, Miura Y, Wagatsuma K, Ishiwata K, Ishii K. Changes in brain amyloid-β accumulation after donepezil administration. J Clin Neurosci. 2017;45:328–9. https://doi.org/10.1016/j.jocn.2017.08.025 .
doi: 10.1016/j.jocn.2017.08.025
pubmed: 28864409
Howard RJ, Juszczak E, Ballard CG, Bentham P, Brown RG, Bullock R, et al. Donepezil for the treatment of agitation in Alzheimer’s disease. N Engl J Med. 2007;357(14):1382–92. https://doi.org/10.1056/NEJMoa066583 .
doi: 10.1056/NEJMoa066583
pubmed: 17914039
De Keyser J, Sulter G, Luiten PG. Clinical trials with neuroprotective drugs in acute ischaemic stroke: are we doing the right thing? Trends Neurosci. 1999;22(12):535–40. https://doi.org/10.1016/s0166-2236(99)01463-0 .
doi: 10.1016/s0166-2236(99)01463-0
pubmed: 10542428
Modell S, Naber D, Holzbach R. Efficacy and safety of an opiate sigma-receptor antagonist (SL 82.0715) in schizophrenic patients with negative symptoms: an open dose-range study. Pharmacopsychiatry. 1996;29(02):63–6. https://doi.org/10.1055/s-2007-979546 .
doi: 10.1055/s-2007-979546
pubmed: 8741023
Hashimoto K, London ED. Interactions of erythro-ifenprodil, threo-ifenprodil, erythro-iodoifenprodil, and eliprodil with subtypes of σ receptors. Eur J Pharmacol. 1995;273(3):307–10. https://doi.org/10.1016/0014-2999(94)00763-w .
doi: 10.1016/0014-2999(94)00763-w
pubmed: 7737340
Brooks S, Kaur S, Starr BS, Starr MS. Motor actions of eliprodil in the normal and monoamine-depleted mouse: a role in the treatment of Parkinson’s disease? J Neural Transm (Vienna). 1996;103(6):737–48. https://doi.org/10.1007/bf01271233 .
doi: 10.1007/bf01271233
pubmed: 8836935
Demerens C, Stankoff B, Zalc B, Lubetzki C. Eliprodil stimulates CNS myelination: new prospects for multiple sclerosis? Neurology. 1999;52(2):346. https://doi.org/10.1212/wnl.52.2.346 .
doi: 10.1212/wnl.52.2.346
pubmed: 9932955
Silkina I, Gan’shina T, Seredin S, Mirzoian R. Gabaergic mechanism of cerebrovascular and neuroprotective effects of afobazole and picamilon. E Eksp Klin Farmakol. 2005;68(1):20–4.
Antipova T, Sapozhnikova D, Liu B, Seredenin S. Selective anxiolytic afobazole increases the content of BDNF and NGF in cultured hippocampal HT-22 line neurons. Eksp Klin Farmakol. 2009;72(1):12–4.
pubmed: 19334503
Cuevas J, Rodriguez A, Behensky A, Katnik C. Afobazole modulates microglial function via activation of both σ-1 and σ-2 receptors. J Pharmacol Exp Ther. 2011;339(1):161–72. https://doi.org/10.1124/jpet.111.182816 .
doi: 10.1124/jpet.111.182816
pubmed: 21715561
Behensky AA, Yasny IE, Shuster AM, Seredenin SB, Petrov AV, Cuevas J. Stimulation of sigma receptors with afobazole blocks activation of microglia and reduces toxicity caused by amyloid-β25–35. J Pharmacol Exp Ther. 2013;347(2):458–67. https://doi.org/10.1124/jpet.113.208348 .
doi: 10.1124/jpet.113.208348
pubmed: 24006337
Behensky AA, Yasny IE, Shuster AM, Seredenin SB, Petrov AV, Cuevas J. Afobazole activation of σ-1 receptors modulates neuronal responses to amyloid-β25–35. J Pharmacol Exp Ther. 2013;347(2):468–77. https://doi.org/10.1124/jpet.113.208330 .
doi: 10.1124/jpet.113.208330
pubmed: 24006338
Martin P, de-Witte PAM, Maurice T, Gammaitoni A, Farfel G, Galer B. Fenfluramine acts as a positive modulator of sigma-1 receptors. Epilepsy Behav. 2020;105:106989. https://doi.org/10.1016/j.yebeh.2020.106989 .
Maurice T. Bi-phasic dose response in the preclinical and clinical developments of sigma-1 receptor ligands for the treatment of neurodegenerative disorders. Expert Opin Drug Discov. 2021;16(4):373–89. https://doi.org/10.1080/17460441.2021.1838483 .
doi: 10.1080/17460441.2021.1838483
pubmed: 33070647
Knupp KG, Scheffer IE, Ceulemans B, Sullivan JE, Nickels KC, Lagae L, et al. Efficacy and safety of fenfluramine for the treatment of seizures associated with Lennox-Gastaut syndrome: a randomized clinical trial. JAMA Neurol. 2022;79(6):554–64. https://doi.org/10.1001/jamaneurol.2022.0829 .
doi: 10.1001/jamaneurol.2022.0829
pubmed: 35499850
pmcid: 9062770
Lagae L, Sullivan J, Knupp K, Laux L, Polster T, Nikanorova M, et al. Fenfluramine hydrochloride for the treatment of seizures in Dravet syndrome: a randomised, double-blind, placebo-controlled trial. Lancet. 2019;394(10216):2243–54. https://doi.org/10.1016/S0140-6736(19)32500-0 .
doi: 10.1016/S0140-6736(19)32500-0
pubmed: 31862249
Specchio N, Pietrafusa N, Doccini V, Trivisano M, Darra F, Ragona F, et al. Efficacy and safety of Fenfluramine hydrochloride for the treatment of seizures in Dravet syndrome: a real-world study. Epilepsia. 2020;61(11):2405–14. https://doi.org/10.1111/epi.16690 .
doi: 10.1111/epi.16690
pubmed: 32945537
Chomchoei C, Brimson J, Brimson S. Repurposing fluoxetine to treat lymphocytic leukaemia: apoptosis induction, sigma-1 receptor upregulation, inhibition of IL-2 cytokine production, and autophagy induction. Expert Opin Ther Targets. 2023. https://doi.org/10.1080/14728222.2022.2166829 .
doi: 10.1080/14728222.2022.2166829
Németh ZK, Szûcs A, Vitrai J, Juhász D, Németh JP, Holló A. Fluoxetine use is associated with improved survival of patients with COVID-19 pneumonia: a retrospective case-control study. Ideggyogy Sz. 2021;74(11–12):389–96. https://doi.org/10.18071/isz.74.0389 .
doi: 10.18071/isz.74.0389
pubmed: 34856085
Emilia M, Rosso D, Laura M, María A. Immunomodulatory effects of fluoxetine: a new potential pharmacological action for a classic antidepressant drug ? Pharmacol Res. 2016;109:101–7. https://doi.org/10.1016/j.phrs.2015.11.021 .
doi: 10.1016/j.phrs.2015.11.021
Safrany ST, Brimson JM. Are fluoxetine’s effects due to sigma-1 receptor agonism? Pharmacol Res. 2016;113:707–8. https://doi.org/10.1016/j.phrs.2016.05.031 .
doi: 10.1016/j.phrs.2016.05.031
pubmed: 27262678
Mostert JP, Admiraal-Behloul F, Hoogduin JM, Luyendijk J, Heersema DJ, Van Buchem MA, et al. Effects of fluoxetine on disease activity in relapsing multiple sclerosis: a double-blind, placebo-controlled, exploratory study. J Neurol Neurosurg Psychiatry. 2008;79(9):1027–31. https://doi.org/10.1136/jnnp.2007.139345 .
doi: 10.1136/jnnp.2007.139345
pubmed: 18450787
Lee JY, Kang SR, Yune TY. Fluoxetine prevents oligodendrocyte cell death by inhibiting microglia activation after spinal cord injury. J Neurotrauma. 2015;32(9):633–44. https://doi.org/10.1089/neu.2014.3527 .
doi: 10.1089/neu.2014.3527
pubmed: 25366938
pmcid: 4410451
Sijens PE, Mostert JP, Irwan R, Potze JH, Oudkerk M, De Keyser J. Impact of fluoxetine on the human brain in multiple sclerosis as quantified by proton magnetic resonance spectroscopy and diffusion tensor imaging. Psychiatry Res. 2008;164(3):274–82. https://doi.org/10.1016/j.pscychresns.2007.12.014 .
doi: 10.1016/j.pscychresns.2007.12.014
pubmed: 19017554
Cambron M, Mostert J, D’Hooghe M, Nagels G, Willekens B, Debruyne J, et al. Fluoxetine in progressive multiple sclerosis: the FLUOX-PMS trial. Mult Scler J. 2019;25(13):1728–35. https://doi.org/10.1177/1352458519843051 .
doi: 10.1177/1352458519843051
Connick P, De Angelis F, Parker RA, Plantone D, Doshi A, John N, et al. Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial (MS-SMART): a multiarm phase IIb randomised, double-blind, placebo-controlled clinical trial comparing the efficacy of three neuroprotective drugs in secondary progressive multiple sclerosis. BMJ Open. 2018;8(8):e021944. https://doi.org/10.1136/bmjopen-2018-021944.
De Angelis F, Connick P, Parker RA, Plantone D, Doshi A, John N, et al. Amiloride, fluoxetine or riluzole to reduce brain volume loss in secondary progressive multiple sclerosis: the MS-SMART four-arm RCT. Efficacy Mech Eval. 2020;7(3):1–72. https://doi.org/10.3310/eme07030 .
doi: 10.3310/eme07030
Chataway J, De Angelis F, Connick P, Parker RA, Plantone D, Doshi A, et al. Efficacy of three neuroprotective drugs in secondary progressive multiple sclerosis (MS-SMART): a phase 2b, multiarm, double-blind, randomised placebo-controlled trial. Lancet Neurol. 2020;19(3):214–25. https://doi.org/10.1016/S1474-4422(19)30485-5 .
doi: 10.1016/S1474-4422(19)30485-5
pubmed: 31981516
pmcid: 7029307
Brimson JM, Prasanth MI, Malar DS, Brimson S, Thitilertdecha P, Tencomnao T. Drugs that offer the potential to reduce hospitalization and mortality from SARS-CoV-2 infection: the possible role of the Sigma-1 receptor and autophagy. Expert Opin Ther Targets. 2021;25(6):35–449. https://doi.org/10.1080/14728222.2021.1952987 .
doi: 10.1080/14728222.2021.1952987
Nishimura T, Ishima T, Iyo M, Hashimoto K. Potentiation of nerve growth factor-induced neurite outgrowth by fluvoxamine: role of sigma-1 receptors, IP3 receptors and cellular signaling pathways. PLoS ONE. 2008;3(7):e2558. https://doi.org/10.1371/journal.pone.0002558 .
doi: 10.1371/journal.pone.0002558
pubmed: 18596927
pmcid: 2435603
Benedetti F, Campori E, Colombo C, Smeraldi E. Fluvoxamine treatment of major depression associated with multiple sclerosis. J Neuropsychiatry Clin Neurosci. 2004;16(3):364–6. https://doi.org/10.1176/jnp.16.3.364 .
doi: 10.1176/jnp.16.3.364
pubmed: 15377746
Ghareghani M, Zibara K, Sadeghi H, Dokoohaki S, Sadeghi H, Aryanpour R, et al. Fluvoxamine stimulates oligodendrogenesis of cultured neural stem cells and attenuates inflammation and demyelination in an animal model of multiple sclerosis. Sci Rep. 2017;7(1):4923. https://doi.org/10.1038/s41598-017-04968-z .
doi: 10.1038/s41598-017-04968-z
pubmed: 28687730
pmcid: 5501834
Robson MJ, Elliott M, Seminerio MJ, Matsumoto RR. Evaluation of sigma (σ) receptors in the antidepressant-like effects of ketamine in vitro and in vivo. Eur Neuropsychopharmacol. 2012;22(4):308–17. https://doi.org/10.1016/j.euroneuro.2011.08.002 .
doi: 10.1016/j.euroneuro.2011.08.002
pubmed: 21911285
Nikiforuk A, Popik P. Ketamine prevents stress-induced cognitive inflexibility in rats. Psychoneuroendocrinology. 2014;40:119–22. https://doi.org/10.1016/j.psyneuen.2013.11.009 .
doi: 10.1016/j.psyneuen.2013.11.009
pubmed: 24485483
Shibakawa YS, Sasaki Y, Goshima Y, Echigo N, Kamiya Y, Kurahashi K, et al. Effects of ketamine and propofol on inflammatory responses of primary glial cell cultures stimulated with lipopolysaccharide. Br J Anaesth. 2005;95(6):803–10. https://doi.org/10.1093/bja/aei256 .
doi: 10.1093/bja/aei256
pubmed: 16227338
Hollinger A, Rüst CA, Riegger H, Gysi B, Tran F, Brügger J, et al. Ketamine vs haloperidol for prevention of cognitive dysfunction and postoperative delirium: a phase IV multicentre randomised placebo-controlled double-blind clinical trial. J Clin Anesth. 2021;68:110099. https://doi.org/10.1016/j.jclinane.2020.110099 .
doi: 10.1016/j.jclinane.2020.110099
pubmed: 33120302
Lara DR, Bisol LW, Munari LR. Antidepressant, mood stabilizing and procognitive effects of very low dose sublingual ketamine in refractory unipolar and bipolar depression. Int J Neuropsychopharmacol. 2013;16(9):2111–7. https://doi.org/10.1017/S1461145713000485 .
doi: 10.1017/S1461145713000485
pubmed: 23683309
Zhang MW, Ho RC. Controversies of the effect of ketamine on cognition. Front Psychiatry. 2016;7:47. https://doi.org/10.3389/fpsyt.2016.00047 .
doi: 10.3389/fpsyt.2016.00047
pubmed: 27065891
pmcid: 4809869
Ownby RL, Crocco E, Acevedo A, John V, Loewenstein D. Depression and risk for Alzheimer disease: systematic review, meta-analysis, and metaregression analysis. Arch Gen Psychiatry. 2006;63(5):530–8. https://doi.org/10.1001/archpsyc.63.5.530 .
doi: 10.1001/archpsyc.63.5.530
pubmed: 16651510
pmcid: 3530614
Aan Het Rot M, Zarate CA, Charney DS, Mathew SJ. Ketamine for depression: where do we go from here? Biol Psychiatry. 2012;72(7):537–47. https://doi.org/10.1016/j.biopsych.2012.05.003.
Rocha FL, de Vasconcelos Cunha UG, Paschoalin RC, Hara C, Thomaz DP. Use of subcutaneous ketamine to rapidly improve severe treatment-resistant depression in a patient with Alzheimer’s disease. Int Clin Psychopharmacol. 2021;36(2):104–5. https://doi.org/10.1097/YIC.0000000000000334 .
doi: 10.1097/YIC.0000000000000334
pubmed: 33230024
He Y, Li H, Huang J, Huang S, Bai Y, Li Y, et al. Efficacy of antidepressant drugs in the treatment of depression in Alzheimer disease patients: a systematic review and network meta-analysis. J Psychopharmacol. 2021;35(8):901–9. https://doi.org/10.1177/02698811211030181 .
doi: 10.1177/02698811211030181
pubmed: 34238048
Yeung L, Wai MS, Fan M, Mak Y, Lam W, Li Z, et al. Hyperphosphorylated tau in the brains of mice and monkeys with long-term administration of ketamine. Toxicol Lett. 2010;193(2):189–93. https://doi.org/10.1016/j.toxlet.2010.01.008 .
doi: 10.1016/j.toxlet.2010.01.008
pubmed: 20093173
Ferro M, Angelucci M, Anselmo-Franci J, Canteras N, Da Cunha C. Neuroprotective effect of ketamine/xylazine on two rat models of Parkinson’s disease. Braz J Med Biol Res. 2007;40:89–96. https://doi.org/10.1590/s0100-879x2007000100012 .
doi: 10.1590/s0100-879x2007000100012
pubmed: 17225001
Vecchia DD, Kanazawa LKS, Wendler E, Hocayen PdAS, Vital MABF, Takahashi RN, et al. Ketamine reversed short-term memory impairment and depressive-like behavior in animal model of Parkinson’s disease. Brain Res Bull. 2021;168:63–73. https://doi.org/10.1016/j.brainresbull.2020.12.011.
Fan J-C, Song J-J, Wang Y, Chen Y, Hong D-X. Neuron-protective effect of subanesthestic-dosage ketamine on mice of Parkinson’s disease. Asian Pac J Trop Med. 2017;10(10):1007–10. https://doi.org/10.1016/j.apjtm.2017.09.014 .
doi: 10.1016/j.apjtm.2017.09.014
pubmed: 29111184
Wright JJ, Goodnight PD, McEvoy MD. The utility of ketamine for the preoperative management of a patient with Parkinson’s disease. Anesth Analg. 2009;108(3):980–2. https://doi.org/10.1213/ane.0b013e3181924025 .
doi: 10.1213/ane.0b013e3181924025
pubmed: 19224812
Salazar G, Motamed C. A remifentanil/ketamine sedation in surgical cancer patients having severe Parkinson’s disease: two case reports. J Opioid Manag. 2012;8(2):133–4. https://doi.org/10.5055/jom.2012.0106 .
doi: 10.5055/jom.2012.0106
pubmed: 22616319
Barenboim I, Lafer B. Maintenance use of ketamine for treatment-resistant depression: an open-label pilot study. Braz J Psychiatry. 2018;40(1):110. https://doi.org/10.1590/1516-4446-2017-2380 .
doi: 10.1590/1516-4446-2017-2380
pubmed: 29590266
pmcid: 6899427
Mathew SJ, Shah A, Lapidus K, Clark C, Jarun N, Ostermeyer B, et al. Ketamine for treatment-resistant unipolar depression. CNS Drugs. 2012;26(3):189–204. https://doi.org/10.2165/11599770-000000000-00000 .
doi: 10.2165/11599770-000000000-00000
pubmed: 22303887
pmcid: 3677048
Feifel D. Breaking sad: unleashing the breakthrough potential of k etamine’s rapid antidepressant effects. Drug Dev Res. 2016;77(8):489–94. https://doi.org/10.1002/ddr.21347 .
doi: 10.1002/ddr.21347
pubmed: 27888525
Shiroma PR, Johns B, Kuskowski M, Wels J, Thuras P, Albott CS, et al. Augmentation of response and remission to serial intravenous subanesthetic ketamine in treatment resistant depression. J Affect Disord. 2014;155:123–9. https://doi.org/10.1016/j.jad.2013.10.036 .
doi: 10.1016/j.jad.2013.10.036
pubmed: 24268616
Wang X, Chang L, Tan Y, Qu Y, Shan J, Hashimoto K. (R)-ketamine ameliorates the progression of experimental autoimmune encephalomyelitis in mice. Brain Res Bull. 2021;177:316–23. https://doi.org/10.1016/j.brainresbull.2021.10.013 .
doi: 10.1016/j.brainresbull.2021.10.013
pubmed: 34688833
Wang X, Chang L, Wan X, Tan Y, Qu Y, Shan J, et al. (R)-ketamine ameliorates demyelination and facilitates remyelination in cuprizone-treated mice: a role of gut–microbiota–brain axis. Neurobiol Dis. 2022;165:105635. https://doi.org/10.1016/j.nbd.2022.105635 .
doi: 10.1016/j.nbd.2022.105635
pubmed: 35085752
Sakai T, Tomiyasu S, Ono T, Yamada H, Sumikawa K. Multiple sclerosis with severe pain and allodynia alleviated by oral ketamine. Clin J Pain. 2004;20(5):375–6. https://doi.org/10.1097/00002508-200409000-00016 .
doi: 10.1097/00002508-200409000-00016
pubmed: 15322448
Messer MM, Haller IV. Ketamine therapy for treatment-resistant depression in a patient with multiple sclerosis: a case report. Innov Clin Neurosci. 2017;14(1–2):56–9.
pubmed: 28386522
pmcid: 5373796
Patrizi A, Picard N, Simon AJ, Gunner G, Centofante E, Andrews NA, et al. Chronic administration of the N-methyl-D-aspartate receptor antagonist ketamine improves Rett syndrome phenotype. Biol Psychiatry. 2016;79(9):755–64. https://doi.org/10.1016/j.biopsych.2015.08.018 .
doi: 10.1016/j.biopsych.2015.08.018
pubmed: 26410354
Kron M, Howell CJ, Adams IT, Ransbottom M, Christian D, Ogier M, et al. Brain activity mapping in Mecp2 mutant mice reveals functional deficits in forebrain circuits, including key nodes in the default mode network, that are reversed with ketamine treatment. J Neurosci. 2012;32(40):13860–72. https://doi.org/10.1523/jneurosci.2159-12.2012 .
doi: 10.1523/jneurosci.2159-12.2012
pubmed: 23035095
pmcid: 3500840
Jolly T, McLean HS. Use of ketamine during procedural sedation: indications, controversies, and side effects. J Infus Nurs. 2012;35(6):377–82. https://doi.org/10.1097/NAN.0b013e31827068c1 .
doi: 10.1097/NAN.0b013e31827068c1
pubmed: 23132086
Mount C, Downton C. Alzheimer disease: progress or profit? Nat Med. 2006;12(7):780–4. https://doi.org/10.1038/nm0706-780 .
doi: 10.1038/nm0706-780
pubmed: 16829947
Guo J, Wang Z, Liu R, Huang Y, Zhang N, Zhang R. Memantine, donepezil, or combination therapy—what is the best therapy for Alzheimer’s disease? A network meta-analysis. Brain Behav. 2020;10(11):e01831. https://doi.org/10.1002/brb3.1831 .
doi: 10.1002/brb3.1831
pubmed: 32914577
pmcid: 7667299
Schmitt HP. On the paradox of ion channel blockade and its benefits in the treatment of Alzheimer disease. Med Hypotheses. 2005;65(2):259–65. https://doi.org/10.1016/j.mehy.2005.03.011 .
doi: 10.1016/j.mehy.2005.03.011
pubmed: 15922097
Parsons C, Danysz W, Quack G. Memantine is a clinically well tolerated N-methyl-D-aspartate (NMDA) receptor antagonist—a review of preclinical data. Neuropharmacol. 1999;38(6):735–67. https://doi.org/10.1016/s0028-3908(99)00019-2 .
doi: 10.1016/s0028-3908(99)00019-2
Rogawski MA, Wenk GL. The neuropharmacological basis for the use of memantine in the treatment of Alzheimer’s disease. CNS Drug Rev. 2003;9(3):275–308. https://doi.org/10.1111/j.1527-3458.2003.tb00254.x .
doi: 10.1111/j.1527-3458.2003.tb00254.x
pubmed: 14530799
pmcid: 6741669
Martina M, Turcotte MEB, Halman S, Bergeron R. The sigma-1 receptor modulates NMDA receptor synaptic transmission and plasticity via SK channels in rat hippocampus. J Physiol. 2007;578(1):143–57. https://doi.org/10.1113/jphysiol.2006.116178 .
doi: 10.1113/jphysiol.2006.116178
pubmed: 17068104
Chaki S, Okuyama S, Ogawa S-i, Tomisawa K. Regulation of NMDA-induced [3H] dopamine release from rat hippocampal slices through sigma-1 binding sites. Neurochem Int. 1998;33(1):29–34. https://doi.org/10.1113/jphysiol.2006.116178.
Sha S, Qu WJ, Li L, Lu ZH, Chen L, Yu WF, et al. Sigma-1 receptor knockout impairs neurogenesis in dentate gyrus of adult hippocampus via down-regulation of NMDA receptors. CNS Neurosci Ther. 2013;19(9):705–13. https://doi.org/10.1111/cns.12129 .
doi: 10.1111/cns.12129
pubmed: 23745740
pmcid: 6493366
Pabba M, Wong AY, Ahlskog N, Hristova E, Biscaro D, Nassrallah W, et al. NMDA receptors are upregulated and trafficked to the plasma membrane after sigma-1 receptor activation in the rat hippocampus. J Neurosci. 2014;34(34):11325–38. https://doi.org/10.1523/JNEUROSCI.0458-14.2014 .
doi: 10.1523/JNEUROSCI.0458-14.2014
pubmed: 25143613
pmcid: 6615506
Stahl SM. Mechanism of action of ketamine. CNS Spectr. 2013;18(4):171–4. https://doi.org/10.1017/S109285291300045X .
doi: 10.1017/S109285291300045X
pubmed: 23866089
Winblad B, Jones RW, Wirth Y, Stöffler A, Möbius HJ. Memantine in moderate to severe Alzheimer’s disease: a meta-analysis of randomised clinical trials. Dement Geriatr Cogn Disord. 2007;24(1):20–7. https://doi.org/10.1159/000102568 .
doi: 10.1159/000102568
pubmed: 17496417
Atri A, Molinuevo JL, Lemming O, Wirth Y, Pulte I, Wilkinson D. Memantine in patients with Alzheimer’s disease receiving donepezil: new analyses of efficacy and safety for combination therapy. Alzheimers Res Ther. 2013;5(1):6. https://doi.org/10.1186/alzrt160 .
doi: 10.1186/alzrt160
pubmed: 23336974
pmcid: 3580327
Schmitt FA, van Dyck CH, Wichems CH, Olin JT, Group MM-M-S. Cognitive response to memantine in moderate to severe Alzheimer disease patients already receiving donepezil: an exploratory reanalysis. Alzheimer Dis Assoc Disord. 2006;20(4):255–62. https://doi.org/10.1097/01.wad.0000213860.35355.d4 .
Lopez OL, Becker JT, Wahed AS, Saxton J, Sweet RA, Wolk DA, et al. Long-term effects of the concomitant use of memantine with cholinesterase inhibition in Alzheimer disease. J Neurol Neurosurg Psychiatry. 2009;80(6):600–7. https://doi.org/10.1136/jnnp.2008.158964 .
doi: 10.1136/jnnp.2008.158964
pubmed: 19204022
Tariot PN, Farlow MR, Grossberg GT, Graham SM, McDonald S, Gergel I, et al. Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. JAMA. 2004;291(3):317–24. https://doi.org/10.1001/jama.291.3.317 .
doi: 10.1001/jama.291.3.317
pubmed: 14734594
Hendrix S, Ellison N, Stanworth S, Otcheretko V, Tariot PN. Post Hoc Evidence for an additive effect of memantine and donepezil: consistent findings from DOMINO-AD Study and Memantine Clinical Trial Program. J Prev Alzheimers Dis. 2015;2(3):165–71. https://doi.org/10.14283/jpad.2015.66 .
doi: 10.14283/jpad.2015.66
pubmed: 29226942
Porsteinsson AP, Grossberg GT, Mintzer J, Olin JT. Memantine treatment in patients with mild to moderate Alzheimer’s disease already receiving a cholinesterase inhibitor: a randomized, double-blind, placebo-controlled trial. Curr Alzheimer Res. 2008;5(1):83–9. https://doi.org/10.2174/156720508783884576 .
doi: 10.2174/156720508783884576
pubmed: 18288936
Leroi I, Overshott R, Byrne EJ, Daniel E, Burns A. Randomized controlled trial of memantine in dementia associated with Parkinson’s disease. Mov Disord. 2009;24(8):1217–21. https://doi.org/10.1002/mds.22495 .
doi: 10.1002/mds.22495
pubmed: 19370737
Emre M, Tsolaki M, Bonuccelli U, Destée A, Tolosa E, Kutzelnigg A, et al. Memantine for patients with Parkinson’s disease dementia or dementia with Lewy bodies: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2010;9(10):969–77. https://doi.org/10.1016/S1474-4422(10)70194-0 .
doi: 10.1016/S1474-4422(10)70194-0
pubmed: 20729148
Ondo WG, Shinawi L, Davidson A, et al. Memantine for non-motor features of Parkinson’s disease: a double-blind placebo controlled exploratory pilot trial. Parkinsonism Relat Disord. 2011;17(3):156–9. https://doi.org/10.1016/j.parkreldis.2010.12.003 .
doi: 10.1016/j.parkreldis.2010.12.003
pubmed: 21193343
Moreau C, Delval A, Tiffreau V, et al. Memantine for axial signs in Parkinson’s disease: a randomised, double-blind, placebo-controlled pilot study. J Neurol Neurosurg Psychiatry. 2013;84(5):552–5. https://doi.org/10.1136/jnnp-2012-303182 .
doi: 10.1136/jnnp-2012-303182
pubmed: 23077087
Wang HF, Yu JT, Tang SW, Jiang T, Tan CC, Meng XF, et al. Efficacy and safety of cholinesterase inhibitors and memantine in cognitive impairment in Parkinson’s disease, Parkinson’s disease dementia, and dementia with Lewy bodies: systematic review with meta-analysis and trial sequential analysis. J Neurol Neurosurg Psychiatry. 2015;86(2):135–43. https://doi.org/10.1136/jnnp-2014-307659 .
doi: 10.1136/jnnp-2014-307659
pubmed: 24828899
Sanjay M, Amir G, John R, Scott O, Stephen D, et al. Short-term tolerability of a nonazapirone selective serotonin 1A agonist in adults with generalized anxiety disorder: a 28-day, open-label study. Clin Ther. 2008;30:9. https://doi.org/10.1016/j.clinthera.2008.09.006 .
doi: 10.1016/j.clinthera.2008.09.006
Rickels K, Mathew S, Banov MD, Zimbroff DL, Oshana S, Parsons EC Jr, et al. Effects of PRX-00023, a novel, selective serotonin 1A receptor agonist on measures of anxiety and depression in generalized anxiety disorder: results of a double-blind, placebo-controlled trial. J Clin Psychopharmacol. 2008;28(2):235–9. https://doi.org/10.1097/JCP.0b013e31816774de .
doi: 10.1097/JCP.0b013e31816774de
pubmed: 18344738
PRX-00023 Therapy in localization-related epilepsy. In: NIH U.S. National Library of Medicine clinical trials web site; 2011. https://clinicaltrials.gov/ct2/show/NCT01281956. Accessed 1 Dec 2022.
Merritt HH, Putnam TJ. Sodium diphenyl hydantoinate in the treatment of convulsive disorders. J Am Med Assoc. 1938;111(12):1068–73. https://doi.org/10.1001/jama.1938.02790380010004 .
doi: 10.1001/jama.1938.02790380010004
Rogawski MA, Löscher W. The neurobiology of antiepileptic drugs. Nat Rev Neurosci. 2004;5(7):553–64. https://doi.org/10.1038/nrn1430 .
doi: 10.1038/nrn1430
pubmed: 15208697
Tchedre KT, Huang RQ, Dibas A, Krishnamoorthy RR, Dillon GH, Yorio T. Sigma-1 receptor regulation of voltage-gated calcium channels involves a direct interaction. Invest Ophthalmol Vis Sci. 2008;49(11):4993–5002. https://doi.org/10.1167/iovs.08-1867 .
doi: 10.1167/iovs.08-1867
pubmed: 18641291
Mueller BH II, Park Y, Daudt DR III, Ma H-Y, Akopova I, Stankowska DL, et al. Sigma-1 receptor stimulation attenuates calcium influx through activated L-type voltage gated calcium channels in purified retinal ganglion cells. Exp Eye Res. 2013;107:21–31. https://doi.org/10.1016/j.exer.2012.11.002 .
doi: 10.1016/j.exer.2012.11.002
pubmed: 23183135
Zhang K, Zhao Z, Lan L, Wei X, Wang L, Liu X, et al. Sigma-1 receptor plays a negative modulation on N-type calcium channel. Front Pharmacol. 2017;8:302. https://doi.org/10.3389/fphar.2017.00302 .
doi: 10.3389/fphar.2017.00302
pubmed: 28603497
pmcid: 5445107
Zhang H, Cuevas J. Sigma receptors inhibit high-voltage–activated calcium channels in rat sympathetic and parasympathetic neurons. J Neurophysiol. 2002;87(6):2867–79. https://doi.org/10.1152/jn.2002.87.6.2867 .
doi: 10.1152/jn.2002.87.6.2867
pubmed: 12037190
DeHaven-Hudkins D, Ford-Rice F, Allen J, Hudkins R. Allosteric modulation of ligand binding to [3H](+) pentazocine-defined σ recognition sites by phenytoin. Life Sci. 1993;53(1):41–8. https://doi.org/10.1016/0024-3205(93)90609-7 .
doi: 10.1016/0024-3205(93)90609-7
pubmed: 8515681
Braakman HM, Verhoeven JS, Erasmus CE, Haaxma CA, Willemsen MH, Schelhaas HJ. Phenytoin as a last-resort treatment in SCN 8A encephalopathy. Epilepsia Open. 2017;2(3):343–4. https://doi.org/10.1002/epi4.12059 .
doi: 10.1002/epi4.12059
pubmed: 29588963
pmcid: 5862112
Dilena R, Striano P, Gennaro E, Bassi L, Olivotto S, Tadini L, et al. Efficacy of sodium channel blockers in SCN2A early infantile epileptic encephalopathy. Brain Dev. 2017;39(4):345–8. https://doi.org/10.1016/j.braindev.2016.10.015 .
doi: 10.1016/j.braindev.2016.10.015
pubmed: 27876397
Su TP, Wu XZ, Cone EJ, Shukla K, Gund TM, Dodge AL, et al. Sigma compounds derived from phencyclidine: identification of PRE-084, a new, selective sigma ligand. J Pharmacol Exp Ther. 1991;259(2):543–50.
pubmed: 1658302
Motawe ZY, Abdelmaboud SS, Cuevas J, Breslin JW. PRE-084 as a tool to uncover potential therapeutic applications for selective sigma-1 receptor activation. Int J Biochem Cell Biol. 2020;126:105803; Doi: https://doi.org/10.1016/j.biocel.2020.105803
Motawe ZY, Farsaei F, Abdelmaboud SS, Cuevas J, Breslin JW. Sigma-1 receptor activation-induced glycolytic ATP production and endothelial barrier enhancement. Microcirculation. 2020;27(6):e12620. https://doi.org/10.1111/micc.12620 .
doi: 10.1111/micc.12620
pubmed: 32279379
pmcid: 7821090
An Y, Qi Y, Li Y, Li Z, Yang C, Jia D. Activation of the sigma-1 receptor attenuates blood–brain barrier disruption by inhibiting amyloid deposition in Alzheimer’s disease mice. Neurosci Lett. 2022;774:136528. https://doi.org/10.1016/j.neulet.2022.136528 .
doi: 10.1016/j.neulet.2022.136528
pubmed: 35157973
Penas C, Pascual-Font A, Mancuso R, Forés J, Casas C, Navarro X. Sigma receptor agonist 2-(4-morpholinethyl) 1 phenylcyclohexanecarboxylate (Pre084) increases GDNF and BiP expression and promotes neuroprotection after root avulsion injury. J Neurotrauma. 2011;28(5):831–40. https://doi.org/10.1089/neu.2010.1674 .
doi: 10.1089/neu.2010.1674
pubmed: 21332255
Francardo V, Bez F, Wieloch T, Nissbrandt H, Ruscher K, Cenci MA. Pharmacological stimulation of sigma-1 receptors has neurorestorative effects in experimental parkinsonism. Brain. 2014;137(7):1998–2014. https://doi.org/10.1093/brain/awu107 .
doi: 10.1093/brain/awu107
pubmed: 24755275
Rao YL, Ganaraja B, Murlimanju BV, Joy T, Krishnamurthy A, Agrawal A. Hippocampus and its involvement in Alzheimer’s disease: a review. 3 Biotech. 2022;12(2):55; Doi: https://doi.org/10.1007/s13205-022-03123-4
Eriksson PS, Perfilieva E, Björk-Eriksson T, Alborn A-M, Nordborg C, Peterson DA, et al. Neurogenesis in the adult human hippocampus. Nat Med. 1998;4(11):1313–7. https://doi.org/10.1038/3305 .
doi: 10.1038/3305
pubmed: 9809557
Borbély E, Varga V, Szögi T, Schuster I, Bozsó Z, Penke B, et al. Impact of two neuronal Sigma-1 receptor modulators, PRE084 and DMT, on neurogenesis and neuroinflammation in an Aβ1–42-injected, wild-type mouse model of AD. Int J Mol Sci. 2022;23(5):2514. https://doi.org/10.3390/ijms23052514 .
doi: 10.3390/ijms23052514
pubmed: 35269657
pmcid: 8910266
Li L, Xu B, Zhu Y, Chen L, Sokabe M, Chen L. DHEA prevents Aβ25–35-impaired survival of newborn neurons in the dentate gyrus through a modulation of PI3K-Akt-mTOR signaling. Neuropharmacol. 2010;59(4–5):323–33. https://doi.org/10.1016/j.neuropharm.2010.02.009 .
doi: 10.1016/j.neuropharm.2010.02.009
Estévez-Silva HM, Cuesto G, Romero N, Brito-Armas JM, Acevedo-Arozena A, Acebes Á, et al. Pridopidine promotes synaptogenesis and reduces spatial memory deficits in the Alzheimer’s disease APP/PS1 mouse model. Neurotherapeutics. 2022;19(5):1566–87. https://doi.org/10.1007/s13311-022-01280-1 .
doi: 10.1007/s13311-022-01280-1
pubmed: 35917088
pmcid: 9606189
Guzmán-Lenis MS, Navarro X, Casas C. Selective sigma receptor agonist 2-(4-morpholinethyl) 1-phenylcyclohexanecarboxylate (PRE084) promotes neuroprotection and neurite elongation through protein kinase C (PKC) signaling on motoneurons. Neuroscience. 2009;162(1):31–8. https://doi.org/10.1016/j.neuroscience.2009.03.067 .
doi: 10.1016/j.neuroscience.2009.03.067
pubmed: 19345724
Mancuso R, Oliván S, Rando A, Casas C, Osta R, Navarro X. Sigma-1R agonist improves motor function and motoneuron survival in ALS mice. Neurotherapeutics. 2012;9(4):814–26. https://doi.org/10.1007/s13311-012-0140-y .
doi: 10.1007/s13311-012-0140-y
pubmed: 22935988
pmcid: 3480575
Mancuso R, Del Valle J, Morell M, Pallás M, Osta R, Navarro X. Lack of synergistic effect of resveratrol and sigma-1 receptor agonist (PRE-084) in SOD1G93A ALS mice: overlapping effects or limited therapeutic opportunity? Orphanet J Rare Dis. 2014;9(1):1–11. https://doi.org/10.1186/1750-1172-9-78 .
doi: 10.1186/1750-1172-9-78
Gaja-Capdevila N, Hernández N, Navarro X, Herrando-Grabulosa M. Sigma-1 receptor is a pharmacological target to promote neuroprotection in the SOD1G93A ALS mice. Front Pharmacol. 2021;12:780588. https://doi.org/10.3389/fphar.2021.780588 .
doi: 10.3389/fphar.2021.780588
pubmed: 34955848
pmcid: 8702863
Peviani M, Salvaneschi E, Bontempi L, Petese A, Manzo A, Rossi D, et al. Neuroprotective effects of the Sigma-1 receptor (S1R) agonist PRE-084, in a mouse model of motor neuron disease not linked to SOD1 mutation. Neurobiol Dis. 2014;62:218–32. https://doi.org/10.1016/j.nbd.2013.10.010 .
doi: 10.1016/j.nbd.2013.10.010
pubmed: 24141020
Barwick SR, Siddiq MS, Wang J, Xiao H, Marshall B, Perry E, et al. Sigma 1 receptor co-localizes with NRF2 in retinal photoreceptor cells. Antioxidants. 2021;10(6):981. https://doi.org/10.3390/antiox10060981 .
doi: 10.3390/antiox10060981
pubmed: 34205384
pmcid: 8234060
Weng TY, Hung DT, Su TP, Tsai SYA. Loss of Sigma-1 receptor chaperone promotes astrocytosis and enhances the Nrf2 antioxidant defense. Oxid Med Cell Longev. 2017;2017:4582135. https://doi.org/10.1155/2017/4582135 .
doi: 10.1155/2017/4582135
pubmed: 28883901
pmcid: 5573104
Lasbleiz C, Peyrel A, Tarot P, Sarniguet J, Crouzier L, Cubedo N, et al. Sigma-1 receptor agonist PRE-084 confers protection against TAR DNA-binding protein-43 toxicity through NRF2 signalling. Redox Biol. 2022;58:102542. https://doi.org/10.1016/j.redox.2022.102542 .
doi: 10.1016/j.redox.2022.102542
pubmed: 36442393
pmcid: 9706169
Hyrskyluoto A, Pulli I, Törnqvist K, Ho H, Korhonen L, Lindholm D. Sigma-1 receptor agonist PRE084 is protective against mutant huntingtin-induced cell degeneration: involvement of calpastatin and the NF-κB pathway. Cell Death Dis. 2013;4(5):e646. https://doi.org/10.1038/cddis.2013.170 .
doi: 10.1038/cddis.2013.170
pubmed: 23703391
pmcid: 3674377
Bol’Shakova A, Kraskovskaya N, Gainullina A, Kukanova E, Vlasova O, Bezprozvanny I. Neuroprotective effect of σ1-receptors on the cell model of Huntington’s disease. Bull Exp Biol Med. 2017;164:252–8. https://doi.org/10.1007/s10517-017-3968-7 .
Johnston TH, Geva M, Steiner L, Orbach A, Papapetropoulos S, Savola JM, et al. Pridopidine, a clinic-ready compound, reduces 3, 4-dihydroxyphenylalanine-induced dyskinesia in Parkinsonian macaques. Mov Disord. 2019;34(5):708–16. https://doi.org/10.1002/mds.27565 .
doi: 10.1002/mds.27565
pubmed: 30575996
Grachev ID, Meyer PM, Becker GA, Bronzel M, Marsteller D, Pastino G, et al. Sigma-1 and dopamine D2/D3 receptor occupancy of pridopidine in healthy volunteers and patients with Huntington disease: a [(18)F] fluspidine and [(18)F] fallypride PET study. Eur J Nucl Med Mol Imaging. 2021;48(4):1103–15. https://doi.org/10.1007/s00259-020-05030-3 .
doi: 10.1007/s00259-020-05030-3
pubmed: 32995944
Sahlholm K, Sijbesma JWA, Maas B, Kwizera C, Marcellino D, Ramakrishnan NK, et al. Pridopidine selectively occupies sigma-1 rather than dopamine D2 receptors at behaviorally active doses. Psychopharmacology. 2015;232(18):3443–53. https://doi.org/10.1007/s00213-015-3997-8 .
doi: 10.1007/s00213-015-3997-8
pubmed: 26159455
pmcid: 4537502
Bourne J, Harris KM. Do thin spines learn to be mushroom spines that remember? Curr Opin Neurobiol. 2007;17(3):381–6. https://doi.org/10.1016/j.conb.2007.04.009 .
doi: 10.1016/j.conb.2007.04.009
pubmed: 17498943
Bourne JN, Harris KM. Balancing structure and function at hippocampal dendritic spines. Annu Rev Neurosci. 2008;31:47–67. https://doi.org/10.1146/annurev.neuro.31.060407.125646 .
doi: 10.1146/annurev.neuro.31.060407.125646
pubmed: 18284372
pmcid: 2561948
Hayashi-Takagi A, Yagishita S, Nakamura M, Shirai F, Wu YI, Loshbaugh AL, et al. Labelling and optical erasure of synaptic memory traces in the motor cortex. Nature. 2015;525(7569):333–8. https://doi.org/10.1038/nature15257 .
doi: 10.1038/nature15257
pubmed: 26352471
pmcid: 4634641
Ionescu A, Gradus T, Altman T, Maimon R, Avraham NS, Geva M, et al. Targeting the sigma-1 receptor via pridopidine ameliorates central features of ALS pathology in a SOD1G93A model. Cell Death Dis. 2019;10(3):210. https://doi.org/10.1038/s41419-019-1451-2 .
doi: 10.1038/s41419-019-1451-2
pubmed: 30824685
pmcid: 6397200
Estévez-Silva HM, Mediavilla T, Giacobbo BL, Liu X, Sultan FR, Marcellino DJ. Pridopidine modifies disease phenotype in a SOD1 mouse model of amyotrophic lateral sclerosis. Eur J Neurosci. 2022;55(5):1356–72. https://doi.org/10.1111/ejn.15608 .
doi: 10.1111/ejn.15608
pubmed: 35080077
pmcid: 9305776
Wang S-M, Wu H-E, Yasui Y, Geva M, Hayden M, Maurice T, et al. Nucleoporin POM121 signals TFEB-mediated autophagy via activation of SIGMAR1/sigma-1 receptor chaperone by pridopidine. Autophagy. 2023;19(1):126–51. https://doi.org/10.1080/15548627.2022.2063003 .
doi: 10.1080/15548627.2022.2063003
pubmed: 35507432
Garcia-Miralles M, Geva M, Tan JY, Yusof NABM, Cha Y, Kusko R, et al. Early pridopidine treatment improves behavioral and transcriptional deficits in YAC128 Huntington disease mice. JCI insight. 2017;2:23. https://doi.org/10.1172/jci.insight.95665 .
doi: 10.1172/jci.insight.95665
Nguyen KQ, Rymar VV, Sadikot AF. Impaired TrkB signaling underlies reduced BDNF-mediated trophic support of striatal neurons in the R6/2 mouse model of Huntington’s disease. Front Cell Neurosci. 2016;10:37. https://doi.org/10.3389/fncel.2016.00037 .
doi: 10.3389/fncel.2016.00037
pubmed: 27013968
pmcid: 4783409
Kusko R, Dreymann J, Ross J, Cha Y, Escalante-Chong R, Garcia-Miralles M, et al. Large-scale transcriptomic analysis reveals that pridopidine reverses aberrant gene expression and activates neuroprotective pathways in the YAC128 HD mouse. Mol Neurodegener. 2018;13(1):25. https://doi.org/10.1186/s13024-018-0259-3 .
doi: 10.1186/s13024-018-0259-3
pubmed: 29783994
pmcid: 5963017
Xie Y, Hayden MR, Xu B. BDNF overexpression in the forebrain rescues Huntington’s disease phenotypes in YAC128 mice. J Neurosci. 2010;30(44):14708–18. https://doi.org/10.1523/JNEUROSCI.1637-10.2010 .
doi: 10.1523/JNEUROSCI.1637-10.2010
pubmed: 21048129
pmcid: 2989389
Geva M, Kusko R, Soares H, Fowler KD, Birnberg T, Barash S, et al. Pridopidine activates neuroprotective pathways impaired in Huntington disease. Hum Mol Genet. 2016;25(18):3975–87. https://doi.org/10.1093/hmg/ddw238 .
doi: 10.1093/hmg/ddw238
pubmed: 27466197
pmcid: 5291233
Yagasaki Y, Numakawa T, Kumamaru E, Hayashi T, Su TP, Kunugi H. Chronic antidepressants potentiate via sigma-1 receptors the brain-derived neurotrophic factor-induced signaling for glutamate release. J Biol Chem. 2006;281(18):12941–9. https://doi.org/10.1074/jbc.M508157200 .
doi: 10.1074/jbc.M508157200
pubmed: 16522641
Huntington Study Group HART Investigators. A randomized, double-blind, placebo-controlled trial of pridopidine in Huntington’s disease. Mov Disord. 2013;28(10):1407–15. https://doi.org/10.1002/mds.25362 .
doi: 10.1002/mds.25362
De Yebenes JG, Landwehrmeyer B, Squitieri F, Reilmann R, Rosser A, Barker RA, et al. Pridopidine for the treatment of motor function in patients with Huntington’s disease (MermaiHD): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2011;10(12):1049–57. https://doi.org/10.1016/S1474-4422(11)70233-2 .
doi: 10.1016/S1474-4422(11)70233-2
pubmed: 22071279
Reilmann R, McGarry A, Grachev ID, Savola J-M, Borowsky B, Eyal E, et al. Safety and efficacy of pridopidine in patients with Huntington’s disease (PRIDE-HD): a phase 2, randomised, placebo-controlled, multicentre, dose-ranging study. Lancet Neurol. 2019;18(2):165–76. https://doi.org/10.1016/S1474-4422(18)30391-0 .
doi: 10.1016/S1474-4422(18)30391-0
pubmed: 30563778
McGarry A, Auinger P, Kieburtz K, Geva M, Mehra M, Abler V, et al. Additional safety and exploratory efficacy data at 48 and 60 months from Open-HART, an open-label extension study of pridopidine in Huntington disease. J Huntingtons Dis. 2020;9(2):173–84. https://doi.org/10.3233/JHD-190393 .
doi: 10.3233/JHD-190393
pubmed: 32508327
Ponten H, Kullingsjö J, Sonesson C, Waters S, Waters N, Tedroff J. The dopaminergic stabilizer pridopidine decreases expression of l-DOPA-induced locomotor sensitisation in the rat unilateral 6-OHDA model. Eur J Pharmacol. 2013;698(1–3):278–85. https://doi.org/10.1016/j.ejphar.2012.10.039 .
doi: 10.1016/j.ejphar.2012.10.039
pubmed: 23127496
McFarthing K, Prakash N, Simuni T. Clinical trial highlights – dyskinesia. J Parkinsons Dis. 2019;9:449–65. https://doi.org/10.3233/JPD-199002 .
doi: 10.3233/JPD-199002
pubmed: 31356217
pmcid: 6704371
Nadjar A, Gerfen CR, Bezard E. Priming for l-dopa-induced dyskinesia in Parkinson’s disease: a feature inherent to the treatment or the disease? Prog Neurobiol. 2009;87(1):1–9. https://doi.org/10.1016/j.pneurobio.2008.09.013 .
doi: 10.1016/j.pneurobio.2008.09.013
pubmed: 18938208
Khoury R, Rajamanickam J, Grossberg GT. An update on the safety of current therapies for Alzheimer’s disease: focus on rivastigmine. Ther Adv Drug Saf. 2018;9(3):171–8. https://doi.org/10.1177/2042098617750555 .
doi: 10.1177/2042098617750555
pubmed: 29492246
pmcid: 5810854
Terada K, Migita K, Matsushima Y, Sugimoto Y, Kamei C, Matsumoto T, et al. Cholinesterase inhibitor rivastigmine enhances nerve growth factor-induced neurite outgrowth in PC12 cells via sigma-1 and sigma-2 receptors. PLoS ONE. 2018;13(12):e0209250. https://doi.org/10.1371/journal.pone.0209250 .
doi: 10.1371/journal.pone.0209250
pubmed: 30557385
pmcid: 6296549
Corey-Bloom J. A randomized trial evaluating the efficacy and safety of ENA 713 (rivastigmine tartrate), a new acetylcholinesterase inhibitor, in patients with mild to moderately severe Alzheimer’s disease. Int J Geriatr Psyopharmacol. 1998;1:55–65.
Rösler M, Anand R, Cicin-Sain A, Gauthier S, Agid Y, Dal-Bianco P, et al. Efficacy and safety of rivastigmine in patients with Alzheimer’s disease: international randomised controlled trial. BMJ. 1999;318(7184):633–8. https://doi.org/10.1136/bmj.318.7184.633 .
doi: 10.1136/bmj.318.7184.633
pubmed: 10066203
pmcid: 27767
Finkel SI. Effects of rivastigmine on behavioral and psychological symptoms of dementia in Alzheimer’s disease. Clin Ther. 2004;26(7):980–90. https://doi.org/10.1016/s0149-2918(04)90172-5 .
doi: 10.1016/s0149-2918(04)90172-5
pubmed: 15336465
Yi B, Sahn JJ, Ardestani PM, Evans AK, Scott LL, Chan JZ, et al. Small molecule modulator of sigma 2 receptor is neuroprotective and reduces cognitive deficits and neuroinflammation in experimental models of Alzheimer’s disease. J Neurochem. 2017;140(4):561–75. https://doi.org/10.1111/jnc.13917 .
doi: 10.1111/jnc.13917
pubmed: 27926996
pmcid: 5312682
Yano T, Tanabe H, Kobayashi K, Kobayashi H, Nabetani A, Sakai Y, et al. Sigma-1 receptor is a molecular target for novel neuroprotectant T-817MA. Alzheimer Dement. 2015;11(7):P861. https://doi.org/10.1016/j.jalz.2015.08.038 .
doi: 10.1016/j.jalz.2015.08.038
Nguyen PTH, Kimura T, Ho SA, Tran AH, Ono T, Nishijo H. Ameliorative effects of a neuroprotective agent, T-817MA, on place learning deficits induced by continuous infusion of amyloid-β peptide (1–40) in rats. Hippocampus. 2007;17(6):443–55. https://doi.org/10.1002/hipo.20281 .
doi: 10.1002/hipo.20281
pubmed: 17397046
Kimura T, Hong Nguyen PT, Ho SA, Tran AH, Ono T, Nishijo H. T-817MA, a neurotrophic agent, ameliorates the deficits in adult neurogenesis and spatial memory in rats infused icv with amyloid-β peptide. Br J Pharmacol. 2009;157(3):451–63. https://doi.org/10.1111/j.1476-5381.2009.00141.x .
doi: 10.1111/j.1476-5381.2009.00141.x
pubmed: 19371351
pmcid: 2707991
Schneider LS, Thomas RG, Hendrix S, Rissman RA, Brewer JB, Salmon DP, et al. Safety and efficacy of edonerpic maleate for patients with mild to moderate alzheimer disease: a phase 2 randomized clinical trial. JAMA Neurol. 2019;76(11):1330–9. https://doi.org/10.1001/jamaneurol.2019.1868 .
doi: 10.1001/jamaneurol.2019.1868
pubmed: 31282954
pmcid: 6618817
Schneider L, Porsteinsson A, Farlow M, Shimakura A, Nakagawa M, Iwakami N. The neuroprotective and neurotrophic agent T-817MA for Alzheimer’s disease: randomized, double-blind, placebo-controlled proof-of-concept trial outcomes. Alzheimers Dement. 2013;9(4):P530–1. https://doi.org/10.1016/j.jalz.2013.04.272 .
doi: 10.1016/j.jalz.2013.04.272
Audronytė E, Kaubrys G. Odor identification and discrimination as markers of early Alzheimer’s disease. Alzheimers Dement. 2022;18:e063101. https://doi.org/10.1002/alz.063101 .
doi: 10.1002/alz.063101
Hudd F, Shiel A, Harris M, Bowdler P, Wood B, Tsivos D, et al. novel blood biomarkers that correlate with cognitive performance and hippocampal volumetry: potential for early diagnosis of Alzheimer’s disease. J Alzheimers Dis. 2019;67(3):931–47. https://doi.org/10.3233/JAD-180879 .
doi: 10.3233/JAD-180879
pubmed: 30689581
Pinto JM, Wroblewski KE, Kern DW, Schumm LP, McClintock MK. Olfactory dysfunction predicts 5-year mortality in older adults. PLoS ONE. 2014;9(10):e107541. https://doi.org/10.1371/journal.pone.0107541 .
doi: 10.1371/journal.pone.0107541
pubmed: 25271633
pmcid: 4182669
Adams DR, Kern DW, Wroblewski KE, McClintock MK, Dale W, Pinto JM. Olfactory dysfunction predicts subsequent dementia in older US adults. J Am Geriatr Soc. 2018;66(1):140–4. https://doi.org/10.1111/jgs.15048 .
doi: 10.1111/jgs.15048
pubmed: 28944467
Wang W, Lee J, Harrou F, Sun Y. Early detection of Parkinson’s disease using deep learning and machine learning. IEEE Access. 2020;8:147635–46. https://doi.org/10.1109/ACCESS.2020.3016062 .
doi: 10.1109/ACCESS.2020.3016062
Lin C-H, Wang F-C, Kuo T-Y, Huang P-W, Chen S-F, Fu L-C. Early detection of Parkinson’s disease by neural network models. IEEE Access. 2022;10:19033–44. https://doi.org/10.1109/ACCESS.2022.3150774 .
doi: 10.1109/ACCESS.2022.3150774