Perampanel Reduces Hyperthermia-Induced Seizures in Dravet Syndrome Mouse Model

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

doi:10.3389/fphar.2021.682767

Perampanel Reduces Hyperthermia-Induced Seizures in Dravet Syndrome Mouse Model

Front Pharmacol. 2021 Jul 14:12:682767. doi: 10.3389/fphar.2021.682767. eCollection 2021.

Authors

Shih-Yin Ho^{1

2}, Li Lin², I-Chun Chen², Che-Wen Tsai², Fang-Chia Chang³, Horng-Huei Liou^{1

2

4}

Affiliations

¹ Department of Neurology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
² Department and Graduate Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan.
³ Department of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, Taipei, Taiwan.
⁴ National Taiwan University Hospital Yunlin Branch, Douliu, Taiwan.

Abstract

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 (Scn1a ^E1099X/+ ). We report here that the PER (2 mg/kg) treatment inhibited the spontaneous recurrent seizures and attenuated epileptic activity in Scn1a ^E1099X/+ 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.

Keywords: NBQX; SCN1A; epilepsy; phenytoin; stiripentol; valproic acid.