Perampanel, a novel, non-competitive, selective AMPA receptor antagonist as adjunctive therapy for treatment-resistant partial-onset seizures.

INTRODUCTION: In the search for new antiepileptic drugs (AEDs), AMPA-type receptor antagonists have a novel target and the potential to improve seizure control in patients with refractory seizures. This article reviews preclinical and clinical data for 2-(2-oxo-1-phenyl-5-pyridin-2-yl-1,2-dihydropyridin-3-yl)benzonitrile, perampanel , a new chemical entity developed for the treatment of partial-onset seizures. AREAS COVERED: Perampanel is a selective, non-competitive AMPA receptor antagonist. The preclinical profile of perampanel and its clinical development are reviewed. EXPERT OPINION: Unlike many traditional AEDs, perampanel demonstrated efficacy in a broad spectrum of preclinical seizure models. Phase I and II clinical studies suggested perampanel had a favorable safety and tolerability profile and demonstrated proof of concept for its mechanism of action in patients with treatment-resistant partial-onset seizures. Three Phase III studies have additionally demonstrated that adjunctive perampanel 4 - 12 mg/day is well-tolerated and significantly improves seizure control in these patients. Median reductions in seizure frequency were 23.3% (4 mg), 26.3 - 30.8% (8 mg) and 17.6 - 34.5% (12 mg) versus 9.7 - 21.0% for placebo. Responder rates were 28.5% (4 mg), 33.3 - 37.6% (8 mg) and 33.9 - 36.1% (12 mg) versus 14.7 - 26.4% for placebo. Perampanel may offer an alternative treatment option in the management of patients with refractory partial-onset seizures.