{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T05:35:13Z","timestamp":1783402513695,"version":"3.54.6"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,7,14]],"date-time":"2021-07-14T00:00:00Z","timestamp":1626220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 106-2314-B-002-093-MY3 MOST 109-2314-B-002-123-MY2"],"award-info":[{"award-number":["MOST 106-2314-B-002-093-MY3 MOST 109-2314-B-002-123-MY2"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Treatment options for Dravet syndrome are limited. The aim of this study was to evaluate the antiepileptic effect of the AMPA receptor antagonist perampanel (PER) on a mouse model of Dravet syndrome (<jats:italic>Scn1a<\/jats:italic><jats:sup><jats:italic>E1099X\/+<\/jats:italic><\/jats:sup>). We report here that the PER (2\u00a0mg\/kg) treatment inhibited the spontaneous recurrent seizures and attenuated epileptic activity in <jats:italic>Scn1a<\/jats:italic><jats:sup><jats:italic>E1099X\/+<\/jats:italic><\/jats:sup> mice. In the hyperthermia-induced seizure experiment, PER clearly increased temperature tolerance and significantly ameliorated seizure frequency and discharge duration. PER also demonstrated antiepileptic effects in a cross-over study and a synergistic effect for attenuating heat-induced seizure when given in combination with stiripentol or valproic acid. The results showed that PER effectively decreased the occurrence of spontaneous recurrent seizures and showed significant therapeutic potential for hyperthermia-induced seizures with regard to both susceptibility and severity in a Dravet syndrome mouse model. Potential therapeutic effects of PER for treatment of Dravet syndrome were demonstrated.<\/jats:p>","DOI":"10.3389\/fphar.2021.682767","type":"journal-article","created":{"date-parts":[[2021,7,14]],"date-time":"2021-07-14T12:40:03Z","timestamp":1626266403000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Perampanel Reduces Hyperthermia-Induced Seizures in Dravet Syndrome Mouse Model"],"prefix":"10.3389","volume":"12","author":[{"given":"Shih-Yin","family":"Ho","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I-Chun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Che-Wen","family":"Tsai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang-Chia","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Horng-Huei","family":"Liou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,7,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"100330","DOI":"10.1016\/j.ebr.2019.100330","article-title":"Efficacy and Tolerability of Perampanel in Patients with Genetic Generalized Epilepsy (GGE): A Retrospective, Single-center Study from the United Arab Emirates (UAE)","volume":"12","author":"Alsaadi","year":"2019","journal-title":"Epilepsy Behav. Rep."},{"key":"B2","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/j.yebeh.2014.12.028","article-title":"The European Patient with Dravet Syndrome: Results from a Parent-Reported Survey on Antiepileptic Drug Use in the European Population with Dravet Syndrome","volume":"44","author":"Aras","year":"2015","journal-title":"Epilepsy Behav."},{"key":"B3","doi-asserted-by":"publisher","first-page":"e172","DOI":"10.1111\/epi.14578","article-title":"Perampanel and Decanoic Acid Show Synergistic Action against AMPA Receptors and Seizures","volume":"59","author":"Augustin","year":"2018","journal-title":"Epilepsia"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1140","DOI":"10.1111\/j.1528-1167.2012.03497.x","article-title":"Efficacy of Stiripentol in Hyperthermia-Induced Seizures in a Mouse Model of Dravet Syndrome","volume":"53","author":"Cao","year":"2012","journal-title":"Epilepsia"},{"key":"B5","doi-asserted-by":"publisher","first-page":"2982","DOI":"10.1093\/brain\/awr129","article-title":"Dravet Syndrome as Epileptic Encephalopathy: Evidence from Long-Term Course and Neuropathology","volume":"134","author":"Catarino","year":"2011","journal-title":"Brain"},{"key":"B6","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1016\/j.neuron.2018.10.018","article-title":"The AMPA Receptor Code of Synaptic Plasticity","volume":"100","author":"Diering","year":"2018","journal-title":"Neuron"},{"key":"B7","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1016\/B978-0-444-52891-9.00065-8","article-title":"Dravet Syndrome (Severe Myoclonic Epilepsy in Infancy)","volume":"111","author":"Dravet","year":"2013","journal-title":"Handb Clin. Neurol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"2178","DOI":"10.1111\/epi.13925","article-title":"The Risk of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in New Users of Antiepileptic Drugs","volume":"58","author":"Frey","year":"2017","journal-title":"Epilepsia"},{"key":"B9","first-page":"683","article-title":"Perampanel (Fycompa): A Review of Clinical Efficacy and Safety in Epilepsy","volume":"41","author":"Greenwood","year":"2016","journal-title":"P T"},{"key":"B10","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1016\/j.neuron.2017.04.009","article-title":"Structural and Functional Architecture of AMPA-type Glutamate Receptors and Their Auxiliary Proteins","volume":"94","author":"Greger","year":"2017","journal-title":"Neuron"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1331","DOI":"10.1111\/j.1528-1167.2011.03109.x","article-title":"Perampanel: a Novel, Orally Active, Noncompetitive AMPA-Receptor Antagonist that Reduces Seizure Activity in Rodent Models of Epilepsy","volume":"52","author":"Hanada","year":"2011","journal-title":"Epilepsia"},{"key":"B12","doi-asserted-by":"publisher","first-page":"e00063","DOI":"10.1002\/prp2.63","article-title":"Effect of Perampanel, a Novel AMPA Antagonist, on Benzodiazepine\u2010resistant Status Epilepticus in a Lithium\u2010pilocarpine Rat Model","volume":"2","author":"Hanada","year":"2014","journal-title":"Pharmacol. Res. Perspect."},{"key":"B13","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1002\/acn3.413","article-title":"Screening of Conventional Anticonvulsants in a Genetic Mouse Model of Epilepsy","volume":"4","author":"Hawkins","year":"2017","journal-title":"Ann. Clin. Transl Neurol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"80","DOI":"10.3389\/fncel.2019.00080","article-title":"Perampanel Affects Up-Stream Regulatory Signaling Pathways of GluA1 Phosphorylation in Normal and Epileptic Rats","volume":"13","author":"Kim","year":"2019","journal-title":"Front. Cel. Neurosci."},{"key":"B15","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.eplepsyres.2015.03.005","article-title":"Absence of Liver Toxicity in Perampanel-Treated Subjects: Pooled Results from Partial Seizure Phase III Perampanel Clinical Studies","volume":"113","author":"Laurenza","year":"2015","journal-title":"Epilepsy Res."},{"key":"B16","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1016\/j.yebeh.2018.06.033","article-title":"Efficacy and Tolerability of Perampanel in Children and Adolescents with Pharmacoresistant Epilepsy: The First Real-World Evaluation in Asian Pediatric Neurology Clinics","volume":"85","author":"Lin","year":"2018","journal-title":"Epilepsy Behav."},{"key":"B17","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1016\/j.eplepsyres.2010.04.006","article-title":"Interactions of Stiripentol with Clobazam and Valproate in the Mouse Maximal Electroshock-Induced Seizure Model","volume":"90","author":"Luszczki","year":"2010","journal-title":"Epilepsy Res."},{"key":"B18","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1016\/j.physbeh.2009.09.005","article-title":"A Revised Racine's Scale for PTZ-Induced Seizures in Rats","volume":"98","author":"L\u00fcttjohann","year":"2009","journal-title":"Physiol. Behav."},{"key":"B19","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/S1474-4422(10)70059-4","article-title":"Voltage-gated Sodium Channels as Therapeutic Targets in Epilepsy and Other Neurological Disorders","volume":"9","author":"Mantegazza","year":"2010","journal-title":"Lancet Neurol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1111\/j.1528-1167.2011.02997.x","article-title":"The Genetics of Dravet Syndrome","volume":"52","author":"Marini","year":"2011","journal-title":"Epilepsia"},{"key":"B21","doi-asserted-by":"publisher","first-page":"2508","DOI":"10.1007\/s12035-018-1230-6","article-title":"Perampanel but Not Amantadine Prevents Behavioral Alterations and Epileptogenesis in Pilocarpine Rat Model of Status Epilepticus","volume":"56","author":"Mohammad","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"3994","DOI":"10.1073\/pnas.0813330106","article-title":"Temperature- and Age-dependent Seizures in a Mouse Model of Severe Myoclonic Epilepsy in Infancy","volume":"106","author":"Oakley","year":"2009","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B23","doi-asserted-by":"publisher","first-page":"5903","DOI":"10.1523\/JNEUROSCI.5270-06.2007","article-title":"Nav1.1 Localizes to Axons of Parvalbumin-Positive Inhibitory Interneurons: a Circuit Basis for Epileptic Seizures in Mice Carrying an Scn1a Gene Mutation","volume":"27","author":"Ogiwara","year":"2007","journal-title":"J. Neurosci."},{"key":"B24","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/s0022-510x(96)00211-0","article-title":"Autoradiographic Distribution of [ 3 H]-(S)-zacopride-labelled 5-HT 3 Receptors in Human Brain","volume":"144","author":"Parker","year":"1996","journal-title":"J. Neurol. Sci."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1665","DOI":"10.1111\/epi.16925","article-title":"Development of an Antiseizure Drug Screening Platform for Dravet Syndrome at the NINDS Contract Site for the Epilepsy Therapy Screening Program","volume":"62","author":"Pernici","year":"2021","journal-title":"Epilepsia"},{"key":"B26","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1016\/j.ejpn.2015.02.008","article-title":"Efficacy and Safety of Perampanel in Adolescent Patients with Drug-Resistant Partial Seizures in Three Double-Blind, Placebo-Controlled, Phase III Randomized Clinical Studies and a Combined Extension Study","volume":"19","author":"Rosenfeld","year":"2015","journal-title":"Eur. J. Paediatric Neurol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1111\/epi.12504","article-title":"Adverse Effects and Safety Profile of Perampanel: a Review of Pooled Data","volume":"55","author":"Rugg-Gunn","year":"2014","journal-title":"Epilepsia"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1109","DOI":"10.1111\/epi.16548","article-title":"Effectiveness and Safety of Perampanel Monotherapy for Focal and Generalized Tonic\u2010clonic Seizures: Experience from a National Multicenter Registry","volume":"61","author":"Toledano Delgado","year":"2020","journal-title":"Epilepsia"},{"key":"B29","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.nbd.2015.02.010","article-title":"Functional and Structural Deficits of the Dentate Gyrus Network Coincide with Emerging Spontaneous Seizures in an Scn1a Mutant Dravet Syndrome Model during Development","volume":"77","author":"Tsai","year":"2015","journal-title":"Neurobiol. Dis."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1740","DOI":"10.1111\/epi.14522","article-title":"Perampanel in Routine Clinical Use in Idiopathic Generalized Epilepsy: The 12-month GENERAL Study","volume":"59","author":"Villanueva","year":"2018","journal-title":"Epilepsia"},{"key":"B31","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1007\/s40263-019-00666-8","article-title":"Recent Advances in the Drug Treatment of Dravet Syndrome","volume":"33","author":"Wirrell","year":"2019","journal-title":"CNS Drugs"},{"key":"B32","doi-asserted-by":"publisher","first-page":"S13","DOI":"10.1017\/cjn.2016.249","article-title":"Treatment of Dravet Syndrome","volume":"43","author":"Wirrell","year":"2016","journal-title":"Can. J. Neurol. Sci."},{"key":"B33","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1002\/acn3.51030","article-title":"Abolishing Spontaneous Epileptiform Activity in Human Brain Tissue through AMPA Receptor Inhibition","volume":"7","author":"Wright","year":"2020","journal-title":"Ann. Clin. Transl Neurol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"e1310","DOI":"10.1542\/peds.2015-1807","article-title":"Incidence of Dravet Syndrome in a US Population","volume":"136","author":"Wu","year":"2015","journal-title":"Pediatrics"},{"key":"B35","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1038\/jcbfm.1994.32","article-title":"Delayed Treatment with AMPA, but Not NMDA, Antagonists Reduces Neocortical Infarction","volume":"14","author":"Xue","year":"1994","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"B36","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1097\/FTD.0000000000000556","article-title":"Influence of Inflammation on the Pharmacokinetics of Perampanel","volume":"40","author":"Yamamoto","year":"2018","journal-title":"Ther. Drug Monit."},{"key":"B37","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1186\/s12929-015-0145-z","article-title":"Low-frequency Electroacupuncture Suppresses Focal Epilepsy and Improves Epilepsy-Induced Sleep Disruptions","volume":"22","author":"Yi","year":"2015","journal-title":"J. Biomed. Sci."},{"key":"B38","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.eplepsyres.2019.02.014","article-title":"Efficacy and Tolerability of Perampanel in Pediatric Patients with Dravet Syndrome","volume":"154","author":"Yoshitomi","year":"2019","journal-title":"Epilepsy Res."},{"key":"B39","doi-asserted-by":"publisher","first-page":"1142","DOI":"10.1038\/nn1754","article-title":"Reduced Sodium Current in GABAergic Interneurons in a Mouse Model of Severe Myoclonic Epilepsy in Infancy","volume":"9","author":"Yu","year":"2006","journal-title":"Nat. Neurosci."},{"key":"B40","doi-asserted-by":"publisher","first-page":"e0131566","DOI":"10.1371\/journal.pone.0131566","article-title":"Comparative Long-Term Effectiveness of a Monotherapy with Five Antiepileptic Drugs for Focal Epilepsy in Adult Patients: A Prospective Cohort Study","volume":"10","author":"Zeng","year":"2015","journal-title":"PLoS One"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2021.682767\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,14]],"date-time":"2021-07-14T12:40:07Z","timestamp":1626266407000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2021.682767\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,14]]},"references-count":40,"alternative-id":["10.3389\/fphar.2021.682767"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2021.682767","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,14]]},"article-number":"682767"}}