title: Perampanel, a novel, non-competitive, selective AMPA receptor antagonist as adjunctive therapy for treatment-resistant partial-onset seizures.
abstract: BACKGROUND
  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.
  
  
  METHODS
  Perampanel is a selective, non-competitive AMPA receptor antagonist. The preclinical profile of perampanel and its clinical development are reviewed.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Masaryk University, Central European Institute of Technology, St Anne's Hospital, Brno Epilepsy Center, First Department of Neurology, Pekarska 53, 656 91 Brno, Czech Republic. irektor@med.muni.cz
authors.forename: Ivan
authors.initials: I
authors.lastname: Rektor
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D004828:Epilepsies, Partial / Q000188:drug therapy*; D006801:Humans; D058990:Molecular Targeted Therapy; D009570:Nitriles; D011728:Pyridones / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D016896:Treatment Outcome
chemical_list: D000927:Anticonvulsants; D009570:Nitriles; D011728:Pyridones; D018091:Receptors, AMPA; C551441:perampanel