Overcoming the Psychiatric Side Effects of the Cannabinoid CB1 Receptor Antagonists: Current Approaches for Therapeutics Development.
Allosteric modulators
CB1 receptor
Neutral antagonists
Peripherally restricted antagonists
Psychiatric side effects
Therapeutics development.
Journal
Current topics in medicinal chemistry
ISSN: 1873-4294
Titre abrégé: Curr Top Med Chem
Pays: United Arab Emirates
ID NLM: 101119673
Informations de publication
Date de publication:
2019
2019
Historique:
received:
10
10
2018
revised:
08
11
2018
accepted:
15
11
2018
pubmed:
10
7
2019
medline:
29
10
2019
entrez:
10
7
2019
Statut:
ppublish
Résumé
The Cannabinoid CB1 Receptor (CB1R) is involved in a variety of physiological pathways and has long been considered a golden target for therapeutic manipulation. A large body of evidence in both animal and human studies suggests that CB1R antagonism is highly effective for the treatment of obesity, metabolic disorders and drug addiction. However, the first-in-class CB1R antagonist/inverse agonist, rimonabant, though demonstrating effectiveness for obesity treatment and smoking cessation, displays serious psychiatric side effects, including anxiety, depression and even suicidal ideation, resulting in its eventual withdrawal from the European market. Several strategies are currently being pursued to circumvent the mechanisms leading to these side effects by developing neutral antagonists, peripherally restricted ligands, and allosteric modulators. In this review, we describe the progress in the development of therapeutics targeting the CB1R in the last two decades.
Identifiants
pubmed: 31284863
pii: CTMC-EPUB-99469
doi: 10.2174/1568026619666190708164841
pmc: PMC6771026
mid: NIHMS1052222
doi:
Substances chimiques
Antipsychotic Agents
0
Cannabinoid Receptor Antagonists
0
Receptor, Cannabinoid, CB1
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1418-1435Subventions
Organisme : NIDA NIH HHS
ID : R01 DA040460
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA040693
Pays : United States
Organisme : NIDA NIH HHS
ID : R03 DA045910
Pays : United States
Informations de copyright
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
Références
Pharm Res. 1999 Oct;16(10):1514-9
pubmed: 10554091
Pharmacol Ther. 2001 Apr;90(1):45-60
pubmed: 11448725
Curr Opin Neurobiol. 2002 Jun;12(3):324-30
pubmed: 12049940
Mol Pharmacol. 2002 Dec;62(6):1274-87
pubmed: 12435794
Mol Pharmacol. 2003 Apr;63(4):908-14
pubmed: 12644592
Mol Pharmacol. 2004 Jan;65(1):2-11
pubmed: 14722230
Br J Pharmacol. 2004 Mar;141(5):765-74
pubmed: 14744801
Eur J Pharmacol. 2004 Mar 8;487(1-3):213-21
pubmed: 15033394
J Med Chem. 2004 May 20;47(11):2939-42
pubmed: 15139773
Life Sci. 2005 Feb 4;76(12):1307-24
pubmed: 15670612
Lancet. 2005 Apr 16-22;365(9468):1389-97
pubmed: 15836887
Nat Rev Immunol. 2005 May;5(5):400-11
pubmed: 15864274
Curr Med Chem. 2005;12(12):1361-94
pubmed: 15974990
Mol Pharmacol. 2005 Nov;68(5):1484-95
pubmed: 16113085
Mol Pharmacol. 2005 Dec;68(6):1623-35
pubmed: 16157695
Br J Pharmacol. 2005 Dec;146(7):917-26
pubmed: 16205722
N Engl J Med. 2005 Nov 17;353(20):2121-34
pubmed: 16291982
JAMA. 2006 Feb 15;295(7):761-75
pubmed: 16478899
NeuroRx. 2005 Oct;2(4):541-53
pubmed: 16489364
Neuropharmacology. 2006 Aug;51(2):358-66
pubmed: 16750544
J Med Chem. 2006 Oct 5;49(20):5969-87
pubmed: 17004712
Eur J Pharmacol. 2006 Dec 28;553(1-3):1-9
pubmed: 17081515
Lancet. 2006 Nov 11;368(9548):1660-72
pubmed: 17098084
Trends Pharmacol Sci. 2007 Feb;28(2):83-92
pubmed: 17222464
Br J Pharmacol. 2007 Mar;150(5):586-94
pubmed: 17245367
Trends Cardiovasc Med. 2007 Feb;17(2):35-43
pubmed: 17292044
Physiol Behav. 2007 Jul 24;91(4):383-8
pubmed: 17521686
Neuropsychopharmacology. 2008 Mar;33(4):946-55
pubmed: 17581535
Br J Pharmacol. 2007 Nov;152(5):805-14
pubmed: 17592509
Psychopharmacology (Berl). 2007 Nov;194(4):505-15
pubmed: 17619859
Vasc Health Risk Manag. 2007;3(3):307-11
pubmed: 17703638
Pediatr Res. 2007 Nov;62(5):533-6
pubmed: 17805201
Am J Physiol Regul Integr Comp Physiol. 2007 Dec;293(6):R2185-93
pubmed: 17959701
Physiol Behav. 2008 Mar 18;93(4-5):666-70
pubmed: 18076956
Cell Metab. 2008 Jan;7(1):1-2
pubmed: 18177717
Org Biomol Chem. 2008 Feb 7;6(3):447-50
pubmed: 18219411
Curr Top Med Chem. 2008;8(3):205-30
pubmed: 18289089
Eur J Pharmacol. 2008 Apr 28;584(2-3):338-42
pubmed: 18336811
Curr Diab Rep. 2008 Feb;8(1):12-9
pubmed: 18366993
JAMA. 2008 Apr 2;299(13):1547-60
pubmed: 18387931
Gut. 2008 Aug;57(8):1140-55
pubmed: 18397936
Arthritis Res Ther. 2008;10(2):R43
pubmed: 18416822
J Neuroendocrinol. 2008 May;20 Suppl 1:116-23
pubmed: 18426510
Nat Rev Drug Discov. 2008 May;7(5):438-55
pubmed: 18446159
Behav Brain Res. 2008 Nov 21;193(2):298-305
pubmed: 18602425
Pharmacol Biochem Behav. 2008 Nov;91(1):84-90
pubmed: 18640150
J Clin Invest. 2008 Sep;118(9):3160-9
pubmed: 18677409
Diabetes Care. 2008 Nov;31(11):2169-76
pubmed: 18678611
Pharmacol Biochem Behav. 2009 Jan;91(3):303-6
pubmed: 18703081
J Med Chem. 2009 Jan 22;52(2):234-7
pubmed: 19102698
Circulation. 2009 Jan 6;119(1):28-36
pubmed: 19103987
Arterioscler Thromb Vasc Biol. 2009 Mar;29(3):416-23
pubmed: 19112166
Nat Rev Drug Discov. 2009 Jan;8(1):41-54
pubmed: 19116626
Br J Pharmacol. 2009 Apr;156(7):1154-66
pubmed: 19378378
FASEB J. 2009 Sep;23(9):3020-9
pubmed: 19380512
Bioorg Med Chem Lett. 2010 Jan 15;20(2):479-82
pubmed: 20005704
Neurogastroenterol Motil. 2010 Jul;22(7):787-96, e223
pubmed: 20180825
Pharmacol Biochem Behav. 2010 Jun;95(4):479-84
pubmed: 20347865
Drug Discov Today. 2010 Jun;15(11-12):411-5
pubmed: 20447467
Br J Pharmacol. 2010 Jun;160(3):677-87
pubmed: 20590571
ChemMedChem. 2010 Sep 3;5(9):1439-43
pubmed: 20652930
Pharmacol Biochem Behav. 2010 Nov;97(1):179-84
pubmed: 20713079
Br J Pharmacol. 2010 Sep;161(2):336-49
pubmed: 20735419
Br J Pharmacol. 2010 Oct;161(3):629-42
pubmed: 20880401
Methods Enzymol. 2010;484:31-51
pubmed: 21036225
Pharmacol Biochem Behav. 2011 Jan;97(3):537-43
pubmed: 21056053
Eur J Pharmacol. 2011 Jan 25;651(1-3):96-105
pubmed: 21114999
Psychopharmacology (Berl). 2011 Aug;216(3):355-65
pubmed: 21369753
Br J Pharmacol. 2012 Apr;165(8):2450-61
pubmed: 21470208
Bioorg Med Chem Lett. 2011 Oct 1;21(19):5711-4
pubmed: 21875798
Br J Pharmacol. 2012 Apr;165(7):2274-91
pubmed: 21951309
J Biol Chem. 2012 Apr 6;287(15):12070-82
pubmed: 22343625
J Med Chem. 2012 Mar 22;55(6):2820-34
pubmed: 22372835
Chem Res Toxicol. 2012 Apr 16;25(4):825-7
pubmed: 22404317
J Med Chem. 2012 Jun 14;55(11):5627-31
pubmed: 22571451
Cell Metab. 2012 Aug 8;16(2):167-79
pubmed: 22841573
J Biol Chem. 2012 Oct 26;287(44):36944-67
pubmed: 22952224
Bioorg Med Chem Lett. 2012 Oct 1;22(19):6173-80
pubmed: 22959249
J Med Chem. 2012 Nov 26;55(22):10022-32
pubmed: 23098108
Philos Trans R Soc Lond B Biol Sci. 2012 Dec 5;367(1607):3353-63
pubmed: 23108552
Mol Pharmacol. 2013 Feb;83(2):322-38
pubmed: 23160940
J Neurochem. 2013 Mar;124(5):584-9
pubmed: 23205875
J Pharmacol Exp Ther. 2013 Mar;344(3):561-7
pubmed: 23287700
Eur J Med Chem. 2013 Apr;62:256-69
pubmed: 23357307
PLoS One. 2013;8(4):e60918
pubmed: 23565287
Br J Clin Pharmacol. 2013 Dec;76(6):846-57
pubmed: 23601084
Nutr Diabetes. 2013 May 27;3:e68
pubmed: 23712280
Pharmacol Res. 2013 Aug;74:94-108
pubmed: 23756200
Hepatology. 2014 Jan;59(1):143-53
pubmed: 23832510
Bioorg Med Chem Lett. 2013 Sep 1;23(17):4751-60
pubmed: 23902803
J Med Chem. 2013 Oct 24;56(20):8066-72
pubmed: 24041123
J Med Chem. 2013 Dec 27;56(24):9920-33
pubmed: 24224693
Synapse. 2014 Mar;68(3):89-97
pubmed: 24293119
Science. 2014 Jan 3;343(6166):94-8
pubmed: 24385629
Behav Pharmacol. 2014 Apr;25(2):182-5
pubmed: 24603340
J Med Chem. 2014 Apr 10;57(7):3040-52
pubmed: 24635495
Psychopharmacology (Berl). 2014 Nov;231(22):4291-300
pubmed: 24770676
Naunyn Schmiedebergs Arch Pharmacol. 2014 Jul;387(7):621-8
pubmed: 24853577
ACS Med Chem Lett. 2011 Sep 17;2(11):866-9
pubmed: 24900275
Adv Pharmacol. 2014;70:121-33
pubmed: 24931194
J Biol Chem. 2014 Sep 5;289(36):24845-62
pubmed: 25037227
FASEB J. 2014 Dec;28(12):5361-75
pubmed: 25154875
J Med Chem. 2014 Sep 25;57(18):7758-69
pubmed: 25162172
Behav Pharmacol. 2015 Apr;26(3):289-303
pubmed: 25356730
Proc Natl Acad Sci U S A. 2014 Dec 16;111(50):E5420-8
pubmed: 25422468
Pharmacol Res Perspect. 2014 Dec;2(6):e00069
pubmed: 25431655
Proc Natl Acad Sci U S A. 2015 Jan 6;112(1):285-90
pubmed: 25535367
Int J Neuropsychopharmacol. 2014 Dec 25;18(6):null
pubmed: 25542687
FASEB J. 2015 Apr;29(4):1446-55
pubmed: 25550466
Br J Pharmacol. 2015 May;172(9):2406-18
pubmed: 25572435
Hepatology. 2015 May;61(5):1615-26
pubmed: 25580584
Psychopharmacology (Berl). 2015 Aug;232(15):2751-61
pubmed: 25772338
Bioorg Med Chem. 2015 May 1;23(9):2195-2203
pubmed: 25797163
Mol Pharmacol. 2015 Aug;88(2):368-79
pubmed: 26044547
J Physiol Pharmacol. 2015 Jun;66(3):343-53
pubmed: 26084216
Pharmacol Res. 2015 Sep;99:370-6
pubmed: 26211948
Br J Pharmacol. 2015 Oct;172(20):4790-805
pubmed: 26218440
Am J Physiol Regul Integr Comp Physiol. 2015 Oct 15;309(8):R805-13
pubmed: 26290104
Int J Neuropsychopharmacol. 2015 Sep 10;19(2):null
pubmed: 26362774
Am J Respir Cell Mol Biol. 2015 Oct;53(4):555-62
pubmed: 26426981
Br J Clin Pharmacol. 2016 Apr;81(4):713-23
pubmed: 26617196
Eur J Nutr. 2016 Jun;55(4):1799-805
pubmed: 26759262
Bioorg Med Chem. 2016 Mar 1;24(5):1063-70
pubmed: 26827137
Neuropsychopharmacology. 2016 Aug;41(9):2283-93
pubmed: 26888056
Int J Neuropsychopharmacol. 2016 Dec 30;19(12):
pubmed: 27493155
Sci Rep. 2016 Sep 19;6:33302
pubmed: 27641999
Bioorg Med Chem Lett. 2016 Nov 1;26(21):5346-5349
pubmed: 27671496
Bioorg Med Chem Lett. 2016 Nov 15;26(22):5597-5601
pubmed: 27671499
Med Res Rev. 2017 May;37(3):441-474
pubmed: 27879006
Mol Metab. 2016 Oct 22;5(12):1187-1199
pubmed: 27900261
J Med Chem. 2017 Feb 9;60(3):1089-1104
pubmed: 28059509
Physiol Behav. 2017 Mar 15;171:32-39
pubmed: 28065722
Psychopharmacology (Berl). 2017 Mar;234(6):1029-1043
pubmed: 28144708
Eur Neuropsychopharmacol. 2017 Jul;27(7):667-678
pubmed: 28377074
Nephrol Dial Transplant. 2017 Oct 1;32(10):1655-1665
pubmed: 28387811
Sci Rep. 2017 Jun 21;7(1):3946
pubmed: 28638091
Methods Enzymol. 2017;593:199-215
pubmed: 28750803
J Med Chem. 2017 Sep 14;60(17):7410-7424
pubmed: 28792219
Neuropharmacology. 2017 Oct;125:365-375
pubmed: 28803965
Mol Metab. 2017 Oct;6(10):1113-1125
pubmed: 29031713
Front Pharmacol. 2017 Oct 05;8:707
pubmed: 29051736
Bioorg Med Chem. 2017 Dec 15;25(24):6427-6434
pubmed: 29079014
Neuropharmacology. 2018 Mar 15;131:200-208
pubmed: 29109060
Nutr Diabetes. 2018 Jan 17;8(1):6
pubmed: 29343706
Front Pharmacol. 2018 Mar 20;9:156
pubmed: 29615900
J Med Chem. 2018 May 24;61(10):4370-4385
pubmed: 29688015
Trends Pharmacol Sci. 2018 Aug;39(8):748-765
pubmed: 29885909
Bioorg Med Chem. 2018 Aug 15;26(15):4518-4531
pubmed: 30077609
ACS Chem Neurosci. 2019 Jan 16;10(1):518-527
pubmed: 30188693
Obes Surg. 2019 Jan;29(1):268-276
pubmed: 30244333
Mol Pharmacol. 1998 Dec;54(6):1064-72
pubmed: 9855635