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.