Pregabalin and gabapentin share a structural analogy with GABA but do not act on GABA receptors. Their anticonvulsant and analgesic mechanism involves which molecular target?

• A Blockade of AMPA receptors at the GluA2 subunit
• B Binding to the alpha-2-delta subunit of voltage-gated calcium channels ✓
• C Inhibition of GABA transaminase, increasing synaptic GABA concentrations
• D Allosteric potentiation of GABA-A receptors at the benzodiazepine binding site

Explanation

Pregabalin and gabapentin bind specifically to the alpha-2-delta (alpha2delta) auxiliary subunit of voltage-gated calcium channels. This binding reduces calcium influx at presynaptic terminals of hyperexcited neurons, decreasing release of excitatory neurotransmitters including glutamate, substance P, and norepinephrine. Their analgesic mechanism in neuropathic pain states exploits the upregulation of alpha2delta subunits in dorsal root ganglia after nerve injury. Despite their GABA-like structure, they have no direct activity on GABA receptors, and do not affect GABA transaminase.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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