Novel treatment options for epilepsy: Focus on perampanel

V. Franco, F. Crema, A. Iudice, G. Zaccara, E. Grillo

Research output: Contribution to journalArticlepeer-review


Perampanel is a new chemical entity recently approved in the United States (US) and European Union (EU) as adjunctive treatment of partial-onset seizures with and without secondary generalization in patients with epilepsy aged 12 years and older. Pharmacological studies suggest that perampanel acts with a new mechanism of action via non-competitive antagonism of the ionotropic α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) receptor of glutamate, the main mediator of excitatory neurotransmission in the central nervous system. Perampanel is completely absorbed after oral administration. The drug is 95% bound to plasma proteins and is extensively metabolized by oxidation followed by glucuronidation. Perampanel has an elimination half-life of approximately 52-129 h, allowing once daily dosing, with peak plasma levels observed 0.25-2 h post-dose. Randomized placebo-controlled trials of adjunctive treatment have demonstrated that once-daily perampanel doses of 4-12 mg/day significantly reduced partial-onset seizure frequency in patients with pharmacoresistant epilepsy along with a favorable tolerability profile. In perampanel pivotal trials, the most frequently reported treatment emergent adverse events (>10%) included dizziness, somnolence, fatigue and headache. Perampanel therapeutic response was maintained in patients included in the long term open-label extension studies for up to 4 years. Based on these data, perampanel offers a valuable option in the add-on treatment of partial-onset and secondarily generalized seizures.

Original languageEnglish
Pages (from-to)35-40
Number of pages6
JournalPharmacological Research
Issue number1
Publication statusPublished - Apr 2013


  • AMPA receptors
  • Epilepsy
  • Glutamate
  • Mechanism of action
  • Perampanel

ASJC Scopus subject areas

  • Pharmacology


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