AUTHOR=Ho Shih-Yin , Lin Li , Chen I-Chun , Tsai Che-Wen , Chang Fang-Chia , Liou Horng-Huei 

TITLE=Perampanel Reduces Hyperthermia-Induced Seizures in Dravet Syndrome Mouse Model

JOURNAL=Frontiers in Pharmacology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.682767

DOI=10.3389/fphar.2021.682767

ISSN=1663-9812

ABSTRACT=<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 (<italic>Scn1a</italic><sup><italic>E1099X/+</italic></sup>). We report here that the PER (2 mg/kg) treatment inhibited the spontaneous recurrent seizures and attenuated epileptic activity in <italic>Scn1a</italic><sup><italic>E1099X/+</italic></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.</p>