Perampanel, approved as adjunctive therapy in focal and generalized seizures, acts via a mechanism distinct from all prior antiepileptics. Its mechanism is:

• A Positive allosteric modulation of GABA-B metabotropic receptors
• B Blockade of HCN channels reducing hyperpolarization-activated current Ih
• C Selective blockade of AMPA-type ionotropic glutamate receptors ✓
• D SV2A synaptic vesicle protein binding reducing excitatory vesicle fusion

Explanation

Perampanel is the first clinically approved non-competitive AMPA receptor antagonist; it blocks AMPA-type (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) ionotropic glutamate receptors at a site distinct from the glutamate binding site, thereby reducing excitatory synaptic neurotransmission. This makes it unique among AEDs. GABA-B positive modulators include baclofen. Ih blockade (HCN channels) is relevant to ivabradine and some experimental AEDs. SV2A binding is the mechanism of levetiracetam and brivaracetam.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.