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

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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.