The anticonvulsant mechanism of perampanel — a newer anti-epileptic drug — is unique because it targets:

• A NMDA receptors as a competitive antagonist at the glycine co-agonist site
• B Kainate glutamate receptors in the hippocampus, reducing temporal lobe seizure spread
• C AMPA-type ionotropic glutamate receptors as a selective non-competitive antagonist, reducing excitatory glutamatergic neurotransmission ✓
• D mGluR5 metabotropic glutamate receptors, reducing IP3-mediated calcium release

Explanation

Perampanel is the first approved AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor antagonist for epilepsy. It is a non-competitive (allosteric) blocker — meaning its binding site is distinct from glutamate — making it effective even at high synaptic glutamate concentrations. AMPA receptors mediate fast excitatory neurotransmission, and their blockade reduces neuronal excitability and seizure propagation. This mechanism differs completely from sodium channel blockers, GABA enhancers, or calcium channel modulators. Perampanel is indicated as adjunctive therapy for focal and generalised tonic-clonic seizures.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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Written and medically reviewed by the StethoPrep medical team.