New drug classes for the treatment of partial onset epilepsy: focus on perampanel

• Type of Material: Article
• Authors: Jerry J. Shih, Mayo Clinic Jacksonville; William O. Tatum, Mayo Clinic Jacksonville; Leslie Rudzinski, Emory University
• Language: English
• Date: 2013-01-01
• Publisher: DOVE MEDICAL PRESS LTD
• Publication Version: Final Published Version
• Copyright Statement: © 2013 Shih et al, publisher and licensee Dove Medical Press Ltd.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.2147/TCRM.S37317
• Title of Journal or Parent Work: THERAPEUTICS AND CLINICAL RISK MANAGEMENT
• Volume: 9
• Issue: 1
• Start Page: 285
• End Page: 293
• Keywords: AMPA RECEPTORS; GLUTAMATE RECEPTORS; review; Health Care Sciences & Services; TOLERABILITY; Life Sciences & Biomedicine; perampanel; EFFICACY; Science & Technology; AUTOPHAGY; ADJUNCTIVE PERAMPANEL; mechanism of action; SEIZURES; RANDOMIZED PHASE-III; ANTIEPILEPTIC DRUGS; efficacy; SYNAPTIC-TRANSMISSION
• Research Categories: Biology, Cell; Biology, Neuroscience

Abstract

Perampanel (2-[2-oxo-1-phenyl-5-pyridin-2-yl-1,2-dihydropyridin-3-yl] benzonitrile hydrate) is the latest in the line of new antiepileptic drugs with a novel mechanism of action. Perampanel inhibits α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)-induced increases in intracellular Ca2+ and selectively blocks AMPA receptor-mediated synaptic trans-mission, thus reducing neuronal excitation. Three Phase III multicenter, randomized, double-blind, placebo-controlled trials demonstrated the efficacy and good tolerability of perampanel as adjunctive treatment in patients with refractory partial-onset seizures. The drug is approved for use in the European Union and United States, with expected release onto the American market in June-September 2013, pending US Drug Enforcement Agency classification. The pharmacology of perampanel offers potential as more than just another new antiepileptic drug. This first-in-class drug will provide another option for practitioners of rational polytherapy. As an AMPA-receptor antagonist, perampanel may possess antiepileptogenic properties in addition to its demonstrated antiseizure properties.