Age-dependent anticonvulsant actions of perampanel and brivaracetam in the methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) model of seizures in developing rats.
AMPA receptor antagonist
Beta carboline
Neonatal seizure
SV2A ligand
Journal
Pharmacological reports : PR
ISSN: 2299-5684
Titre abrégé: Pharmacol Rep
Pays: Switzerland
ID NLM: 101234999
Informations de publication
Date de publication:
Feb 2021
Feb 2021
Historique:
received:
07
09
2020
accepted:
31
10
2020
revised:
09
10
2020
pubmed:
20
11
2020
medline:
9
9
2021
entrez:
19
11
2020
Statut:
ppublish
Résumé
The antiseizure drugs commonly used as first- and second-line treatments for neonatal seizures display poor efficacy. Thus, drug mechanisms of action that differ from these typical agents might provide better seizure control. Perampanel, an AMPA-receptor antagonist, and brivaracetam, a SV2A ligand, might fill that role. We utilized methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) to evoke seizures in rats to assess the efficacy of perampanel and brivaracetam treatment in clinically relevant doses. In postnatal day (P)10 rats, neither perampanel nor brivaracetam suppressed seizure activity. By contrast, in P21 rats, both drugs decreased the severity of seizures. This effect was evident at the 20 and 40 mg/kg doses of brivaracetam and at the 0.9 and 2.7 mg/kg doses of perampanel. These data indicate that while the efficacy of these drugs may be limited for neonatal seizures, their efficacy increases over early postnatal development.
Sections du résumé
BACKGROUND
BACKGROUND
The antiseizure drugs commonly used as first- and second-line treatments for neonatal seizures display poor efficacy. Thus, drug mechanisms of action that differ from these typical agents might provide better seizure control. Perampanel, an AMPA-receptor antagonist, and brivaracetam, a SV2A ligand, might fill that role.
METHODS
METHODS
We utilized methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) to evoke seizures in rats to assess the efficacy of perampanel and brivaracetam treatment in clinically relevant doses.
RESULTS
RESULTS
In postnatal day (P)10 rats, neither perampanel nor brivaracetam suppressed seizure activity. By contrast, in P21 rats, both drugs decreased the severity of seizures. This effect was evident at the 20 and 40 mg/kg doses of brivaracetam and at the 0.9 and 2.7 mg/kg doses of perampanel.
CONCLUSIONS
CONCLUSIONS
These data indicate that while the efficacy of these drugs may be limited for neonatal seizures, their efficacy increases over early postnatal development.
Identifiants
pubmed: 33210244
doi: 10.1007/s43440-020-00189-w
pii: 10.1007/s43440-020-00189-w
pmc: PMC7864869
mid: NIHMS1647948
doi:
Substances chimiques
Anticonvulsants
0
Carbolines
0
Convulsants
0
Nitriles
0
Pyridones
0
Pyrrolidinones
0
methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate
1309288N1J
perampanel
H821664NPK
brivaracetam
U863JGG2IA
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
296-302Subventions
Organisme : NINDS NIH HHS
ID : L40 NS103805
Pays : United States
Organisme : American Academy of Pediatrics
ID : Marshall-Klaus Award
Organisme : NCATS NIH HHS
ID : KL2 TR001432
Pays : United States
Organisme : NCATS NIH HHS
ID : TL1 TR001431
Pays : United States
Organisme : National Center for Advancing Translational Sciences (US)
ID : TL1TR001431
Organisme : NCATS NIH HHS
ID : KL2TR001432
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD091994
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS097762
Pays : United States
Organisme : National Institute of Neurological Disorders and Stroke (US)
ID : R01NS097762
Organisme : Eunice Kennedy Shriver National Institute of Child Health and Human Development
ID : R01HD091994
Références
Vasudevan C, Levene M. Epidemiology and aetiology of neonatal seizures. Semin Fetal Neonatal Med. 2013;18(4):185–91.
pubmed: 23746578
doi: 10.1016/j.siny.2013.05.008
pmcid: 23746578
Martin JA, Hamilton BE, Osterman MJK, Driscoll AK. Births: final data for 2018. Natl Vital Stat Rep Cent Dis Control Prev Natl Cent Health Stat Natl Vital Stat Syst. 2019;68(13):1–47.
Painter MJ, Scher MS, Stein AD, Armatti S, Wang Z, Gardiner JC, et al. Phenobarbital compared with phenytoin for the treatment of neonatal seizures. N Engl J Med. 1999;341(7):485–9.
pubmed: 10441604
doi: 10.1056/NEJM199908123410704
pmcid: 10441604
Sankar R, Painter MJ. Neonatal seizures: after all these years we still love what doesn’t work. Neurology. 2005;64(5):776–7.
pubmed: 15753407
doi: 10.1212/01.WNL.0000157320.78071.6D
pmcid: 15753407
Devinsky O, Cross JH, Laux L, Marsh E, Miller I, Nabbout R, et al. Trial of cannabidiol for drug-resistant seizures in the Dravet Syndrome. N Engl J Med. 2017;376(21):2011–20.
doi: 10.1056/NEJMoa1611618
Lattanzi S, Brigo F, Trinka E, Zaccara G, Cagnetti C, Del Giovane C, et al. Efficacy and safety of cannabidiol in epilepsy: a systematic review and meta-analysis. Drugs. 2018;78(17):1791–804.
pubmed: 30390221
doi: 10.1007/s40265-018-0992-5
pmcid: 30390221
Lattanzi S, Brigo F, Grillo E, Cagnetti C, Verrotti A, Zaccara G, et al. Adjunctive eslicarbazepine acetate in pediatric patients with focal epilepsy: a systematic review and meta-analysis. CNS Drugs. 2018;32(3):189–96.
pubmed: 29508243
doi: 10.1007/s40263-018-0504-x
pmcid: 29508243
Hanada T. The discovery and development of perampanel for the treatment of epilepsy. Expert Opin Drug Discov. 2014;9(4):449–58.
pubmed: 24559052
doi: 10.1517/17460441.2014.891580
pmcid: 24559052
Faulkner MA. Spotlight on perampanel in the management of seizures: design, development and an update on place in therapy. Drug Des DevelTher. 2017;11:2921–30.
Klitgaard H, Matagne A, Nicolas J-M, Gillard M, Lamberty Y, De Ryck M, et al. Brivaracetam: rationale for discovery and preclinical profile of a selective SV2A ligand for epilepsy treatment. Epilepsia. 2016;57(4):538–48.
pubmed: 26920914
doi: 10.1111/epi.13340
Klein P, Diaz A, Gasalla T, Whitesides J. A review of the pharmacology and clinical efficacy of brivaracetam. ClinPharmacolAdvAppl. 2018;10:1–22.
Rao VR, Finkbeiner S. NMDA and AMPA receptors: old channels, new tricks. Trends Neurosci. 2007;30(6):284–91.
pubmed: 17418904
doi: 10.1016/j.tins.2007.03.012
Wright A, Vissel B. The essential role of AMPA receptor GluR2 subunit RNA editing in the normal and diseased brain. Front Mol Neurosci [Internet]. 2012 [cited 2020 Aug 23];5. https://journal.frontiersin.org/article/10.3389/fnmol.2012.00034/abstract .
Berg M, Bruhn T, Johansen FF, Diemer NH. Kainic acid-induced seizures and brain damage in the rat: different effects of NMDA- and AMPA receptor antagonists. PharmacolToxicol. 1993;73(5):262–8.
Chen T, Dai S-H, Jiang Z-Q, Luo P, Jiang X-F, Fei Z, et al. The AMPAR antagonist perampanel attenuates traumatic brain injury through anti-oxidative and anti-inflammatory activity. Cell MolNeurobiol. 2017;37(1):43–52.
doi: 10.1007/s10571-016-0341-8
Niu H-X, Wang J-Z, Wang D-L, Miao J-J, Li H, Liu Z-G, et al. The orally active noncompetitive AMPAR antagonist perampanel attenuates focal cerebral ischemia injury in rats. Cell MolNeurobiol. 2018;38(2):459–66.
doi: 10.1007/s10571-017-0489-x
Mohammad H, Sekar S, Wei Z, Moien-Afshari F, Taghibiglou C. Perampanel but not amantadine prevents behavioral alterations and epileptogenesis in pilocarpine rat model of status epilepticus. MolNeurobiol. 2019;56(4):2508–23.
Wood MD, Gillard M. Evidence for a differential interaction of brivaracetam and levetiracetam with the synaptic vesicle 2A protein. Epilepsia. 2017;58(2):255–62.
pubmed: 28012162
doi: 10.1111/epi.13638
Matagne A, Margineanu D-G, Kenda B, Michel P, Klitgaard H. Anti-convulsive and anti-epileptic properties of brivaracetam (ucb 34714), a high-affinity ligand for the synaptic vesicle protein, SV2A: anticonvulsive properties of brivaracetam. Br J Pharmacol. 2009;154(8):1662–71.
doi: 10.1038/bjp.2008.198
Hanada T, Hashizume Y, Tokuhara N, Takenaka O, Kohmura N, Ogasawara A, et al. Perampanel: a novel, orally active, noncompetitive AMPA-receptor antagonist that reduces seizure activity in rodent models of epilepsy. Epilepsia. 2011;52(7):1331–40.
pubmed: 21635236
doi: 10.1111/j.1528-1167.2011.03109.x
pmcid: 21635236
Dupuis N, Mazarati A, Desnous B, Chhor V, Fleiss B, Le Charpentier T, et al. Pro-epileptogenic effects of viral-like inflammation in both mature and immature brains. J Neuroinflammation [Internet]. 2016 [cited 2017 Jan 8];13(1). https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-016-0773-6 .
Dupuis N, Matagne A, Staelens L, Dournaud P, Desnous B, Gressens P, et al. Anti-ictogenic and antiepileptogenic properties of brivaracetam in mature and immature rats. Epilepsia. 2015;56(5):800–5.
pubmed: 25818358
doi: 10.1111/epi.12973
pmcid: 25818358
Kulick C, Gutherz S, Kondratyev A, Forcelli PA. Ontogenic profile of seizures evoked by the beta-carboline DMCM (methyl-6,7-dimethoxy-4-ethyl-β-carboline-3-carboxylate) in rats. Eur J Pharmacol. 2014;5(740):662–8.
doi: 10.1016/j.ejphar.2014.06.012
Kulick CV, Gutherz SB, Beck VC, Medvedeva N, Soper C, Forcelli PA. Profile of anticonvulsant action of levetiracetam, tiagabine and phenobarbital against seizures evoked by DMCM (methyl-6,7-dimethoxy-4-ethyl-β-carboline-3-carboxylate) in neonatal rats. Eur J Pharmacol. 2014;15(743):63–8.
doi: 10.1016/j.ejphar.2014.09.016
Huizenga MN, Wicker E, Beck VC, Forcelli PA. Anticonvulsant effect of cannabinoid receptor agonists in models of seizures in developing rats. Epilepsia. 2017;58(9):1593–602.
pubmed: 28691158
doi: 10.1111/epi.13842
pmcid: 28691158
Huizenga MN, Sepulveda-Rodriguez A, Forcelli PA. Preclinical safety and efficacy of cannabidivarin for early life seizures. Neuropharmacology. 2019;148:189–98.
pubmed: 30633929
pmcid: 6424614
doi: 10.1016/j.neuropharm.2019.01.002
Semple BD, Blomgren K, Gimlin K, Ferriero DM, Noble-Haeusslein LJ. Brain development in rodents and humans: identifying benchmarks of maturation and vulnerability to injury across species. Prog Neurobiol. 2013;106–107:1–16.
pubmed: 23583307
doi: 10.1016/j.pneurobio.2013.04.001
pmcid: 23583307
Dobbing J, Sands J. Comparative aspects of the brain growth spurt. Early Hum Dev. 1979;3(1):79–83.
pubmed: 118862
doi: 10.1016/0378-3782(79)90022-7
pmcid: 118862
Dupuis N, Enderlin J, Thomas J, Desnous B, Dournaud P, Allorge D, et al. Anti-ictogenic and antiepileptogenic properties of perampanel in mature and immature rats. Epilepsia. 2017;58(11):1985–92.
pubmed: 28850671
doi: 10.1111/epi.13894
pmcid: 28850671
Forcelli PA, Soper C, Lakhkar A, Gale K, Kondratyev A. Anticonvulsant effect of retigabine during postnatal development in rats. Epilepsy Res. 2012;101(1–2):135–40.
pubmed: 22483539
doi: 10.1016/j.eplepsyres.2012.03.006
pmcid: 22483539
Forcelli PA, Soper C, Duckles A, Gale K, Kondratyev A. Melatonin potentiates the anticonvulsant action of phenobarbital in neonatal rats. Epilepsy Res. 2013;107(3):217–23.
pubmed: 24206906
doi: 10.1016/j.eplepsyres.2013.09.013
pmcid: 24206906
Kubova H, Mares P. Anticonvulsant effects of phenobarbital and primidone during ontogenesis in rats. Epilepsy Res. 1991;10(2–3):148–55.
pubmed: 1817955
doi: 10.1016/0920-1211(91)90007-3
pmcid: 1817955
Hibi S, Ueno K, Nagato S, Kawano K, Ito K, Norimine Y, et al. Discovery of 2-(2-Oxo-1-phenyl-5-pyridin-2-yl-1,2-dihydropyridin-3-yl)benzonitrile (Perampanel): a novel, noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropanoic Acid (AMPA) receptor antagonist. J Med Chem. 2012;55(23):10584–600.
pubmed: 23181587
doi: 10.1021/jm301268u
pmcid: 23181587
Insel TR, Miller LP, Gelhard RE. The ontogeny of excitatory amino acid receptors in rat forebrain–I. N-methyl-D-aspartate and quisqualate receptors. Neuroscience. 1990;35(1):31–43.
pubmed: 1972786
doi: 10.1016/0306-4522(90)90117-M
pmcid: 1972786
Kubová H, Bendová Z, Moravcová S, Pačesová D, Rocha LL, Mareš P. Neonatal clonazepam administration induces long-lasting changes in glutamate receptors. Front MolNeurosci. 2018;11:382.
Szczurowska E, Ergang P, Kubová H, Druga R, Salaj M, Mareš P. Influence of early life status epilepticus on the developmental expression profile of the GluA2 subunit of AMPA receptors. ExpNeurol. 2016;283(Pt A):97–109.
Ritter LM, Vazquez DM, Meador-Woodruff JH. Ontogeny of ionotropic glutamate receptor subunit expression in the rat hippocampus. Brain Res Dev Brain Res. 2002;139(2):227–36.
pubmed: 12480137
doi: 10.1016/S0165-3806(02)00572-2
pmcid: 12480137
Erdö SL, Wolff JR. Transient increase in ligand binding to quisqualate and kainate sites in cerebral cortex of immature rats. Neurosci Lett. 1989;104(1–2):161–6.
pubmed: 2554218
doi: 10.1016/0304-3940(89)90348-0
pmcid: 2554218
Schwenk J, Baehrens D, Haupt A, Bildl W, Boudkkazi S, Roeper J, et al. Regional diversity and developmental dynamics of the AMPA-receptor proteome in the mammalian brain. Neuron. 2014;84(1):41–54.
pubmed: 25242221
doi: 10.1016/j.neuron.2014.08.044
pmcid: 25242221
Kumar SS, Bacci A, Kharazia V, Huguenard JR. A developmental switch of AMPA receptor subunits in neocortical pyramidal neurons. J NeurosciOff J SocNeurosci. 2002;22(8):3005–15.
doi: 10.1523/JNEUROSCI.22-08-03005.2002
Szczurowska E, Mareš P. An antagonist of calcium permeable AMPA receptors, IEM1460: anticonvulsant action in immature rats? Epilepsy Res. 2015;109:106–13.
pubmed: 25524849
doi: 10.1016/j.eplepsyres.2014.10.020
pmcid: 25524849
Brill J, Huguenard JR. Sequential changes in AMPA receptor targeting in the developing neocortical excitatory circuit. J Neurosci Off J SocNeurosci. 2008;28(51):13918–28.
doi: 10.1523/JNEUROSCI.3229-08.2008
Akgül G, McBain CJ. Diverse roles for ionotropic glutamate receptors on inhibitory interneurons in developing and adult brain. J Physiol. 2016;594(19):5471–90.
pubmed: 26918438
pmcid: 5043048
doi: 10.1113/JP271764
Gillard M, Fuks B, Leclercq K, Matagne A. Binding characteristics of brivaracetam, a selective, high affinity SV2A ligand in rat, mouse and human brain: relationship to anti-convulsant properties. Eur J Pharmacol. 2011;664(1–3):36–44.
pubmed: 21575627
doi: 10.1016/j.ejphar.2011.04.064
pmcid: 21575627
Crèvecœur J, Foerch P, Doupagne M, Thielen C, Vandenplas C, Moonen G, et al. Expression of SV2 isoforms during rodent brain development. BMC Neurosci. 2013;14(1):87.
pubmed: 23937191
pmcid: 3765414
doi: 10.1186/1471-2202-14-87
Wu T, Ido K, Osada Y, Kotani S, Tamaoka A, Hanada T. The neuroprotective effect of perampanel in lithium-pilocarpine rat seizure model. Epilepsy Res. 2017;137:152–8.
pubmed: 28624183
doi: 10.1016/j.eplepsyres.2017.06.002
pmcid: 28624183
Shetty AK. Prospects of levetiracetam as a neuroprotective drug against status epilepticus, traumatic brain injury, and stroke. Front Neurol [Internet]. 2013 [cited 2020 Aug 23];4. https://journal.frontiersin.org/article/10.3389/fneur.2013.00172/abstract .
Bittigau P, Sifringer M, Genz K, Reith E, Pospischil D, Govindarajalu S, et al. Antiepileptic drugs and apoptotic neurodegeneration in the developing brain. Proc Natl Acad Sci U A. 2002;99(23):15089–94.
doi: 10.1073/pnas.222550499
Katz I, Kim J, Gale K, Kondratyev A. Effects of lamotrigine alone and in combination with MK-801, phenobarbital, or phenytoin on cell death in the neonatal rat brain. J PharmacolExpTher. 2007;322(2):494–500.
Kim J, Kondratyev A, Gale K. Antiepileptic drug-induced neuronal cell death in the immature brain: effects of carbamazepine, topiramate, and levetiracetam as monotherapy versus polytherapy. J PharmacolExpTher. 2007;323(1):165–73.
Kaushal S, Tamer Z, Opoku F, Forcelli PA. Anticonvulsant drug-induced cell death in the developing white matter of the rodent brain. Epilepsia. 2016;57(5):727–34.
pubmed: 27012547
pmcid: 5214662
doi: 10.1111/epi.13365
Brown L, Gutherz S, Kulick C, Soper C, Kondratyev A, Forcelli PA. Profile of retigabine-induced neuronal apoptosis in the developing rat brain. Epilepsia. 2016;57(4):660–70.
pubmed: 26865186
pmcid: 5214840
doi: 10.1111/epi.13335
Fycompa (perampanel) [package inset]. [Internet]. Eisai Inc; 2019 [cited 2020 Sep 6]. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/202834s011lbl.pdf .