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

Authors Shih JJ, Tatum WO, Rudzinski LA

Received 8 April 2013

Accepted for publication 11 May 2013

Published 8 July 2013 Volume 2013:9 Pages 285—293

DOI https://doi.org/10.2147/TCRM.S37317

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2


Jerry J Shih,1 William O Tatum,1 Leslie A Rudzinski2

1Department of Neurology, Mayo Clinic, Jacksonville, FL, USA; 2Department of Neurology, Emory University, Atlanta, GA, USA

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 transmission, 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.

Keywords: perampanel, mechanism of action, efficacy, review

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