AMPA receptor inhibitors for the treatment of epilepsy: the role of perampanel

Abstract

α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in the postsynaptic membrane are involved in fast excitatory signaling in the brain and their activation may lead to the firing of action potentials. Talampanel and perampanel were the first noncompetitive AMPA receptor antagonists to be tested as add-on drugs in patients with refractory partial seizures, and were found to be effective in improving seizure control. Due to an unfavorable kinetic and tolerability profile, talampanel clinical development in the field of epilepsy was discontinued early while perampanel has been recently approved in Europe and the USA as adjunctive therapy for adults with partial seizures with or without secondary generalization. The recommended perampanel starting dose is 2 mg/day once daily, which can be increased up to the recommended maintenance dose of 4–8 mg/day. Increments should be of 2 mg/day and based on clinical response and tolerability. Titration should be performed at 1-week intervals or at lower speed and a 12-mg daily dose should be considered after careful evaluation. To date, no serious and/or idiosyncratic adverse effects have been associated with this agent. Most frequently reported adverse effects are dizziness, ataxia, aggression, irritability, vertigo, somnolence, fatigue, headache and gait disturbance. Weight increase is the only non-neurological adverse effects associated with perampanel.

Keywords::

• α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors
• antiepileptic drugs
• drug therapy
• epilepsy
• partial-onset seizures
• perampanel

Financial & competing interests disclosure

G Zaccara has received speaker’s or consultancy fees from EISAI, GSK, Jansen-Cilag, Novartis, Sanofi-Aventis and UCB Pharma. F Giovannelli and M Cincotta report no disclosures. A Iudice has received research grants, speaker’s or consultancy fees from Janssen, UCB Pharma, Eisai, Bayer-Schering, Merck-Serono, Teva and Biogen in the last 2 years.. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.