Perampanel

Perampanel is FDA-approved as adjunctive therapy for the treatment of partial-onset seizures (focal seizures) with or without secondarily generalized seizures in patients with epilepsy aged 4 years and older. It is also approved for use as adjunctive therapy for primary generalized tonic-clonic seizures in patients with idiopathic generalized epilepsy aged 7 years and older.

Perampanel is a selective, non-competitive antagonist of the ionotropic AMPA glutamate receptor. By blocking these receptors on post-synaptic neurons, it reduces the excitatory effects of glutamate—the primary excitatory neurotransmitter in the central nervous system—thereby decreasing neuronal hyperexcitability that contributes to seizure generation and spread.

Perampanel requires gradual dose titration to reduce side effects. Common adverse reactions include dizziness, somnolence, fatigue, and irritability. Notably, psychiatric effects including aggression, hostility, and suicidal ideation have been reported; patients should be monitored for behavioral changes. The drug has a long half-life and should be discontinued gradually to avoid withdrawal seizures. May interact with other antiepileptic drugs and certain medications metabolized by CYP3A4.