Development of perampanel in epilepsy

Alpha‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA)‐type glutamate receptors play a key role in mediating glutamatergic transmission in the cortex. Perampanel (2‐[2‐oxo‐1‐phenyl‐5‐pyridin‐2‐yl‐1,2‐dihydropyridin‐3‐yl] benzonitrile) is a potent, orally active, highly selective, non‐competitive AMPA‐type glutamate receptor antagonist, identified via a focused discovery program at Eisai Research Laboratories. Development of perampanel as adjunctive therapy for the treatment of partial‐onset seizures was planned in keeping with regulatory guidance and guidelines on antiepileptic drug (AED) development. This is the first AED with a specific action on glutamate‐mediated excitatory neurotransmission to show evidence of efficacy and tolerability in reducing treatment‐refractory partial‐onset seizures in Phase III clinical trials. Perampanel (Fycompa®) has been approved in the EU and the United States for adjunctive treatment of partial‐onset seizures.