Valproate is used across multiple seizure types. In addition to sodium channel blockade, it inhibits which enzyme that increases brain GABA levels?

• A GABA transaminase (GABA-T), the mitochondrial enzyme that degrades GABA ✓
• B Glutamate decarboxylase (GAD), which converts glutamate to GABA
• C Succinate semialdehyde dehydrogenase, increasing GABA precursor availability
• D Glutaminase, reducing glutamate available for GABA synthesis

Explanation

Valproate inhibits GABA transaminase (GABA-T), the enzyme responsible for GABA catabolism, thereby increasing synaptic GABA concentrations. It also blocks voltage-gated sodium and T-type calcium channels and may enhance GABA synthesis. Vigabatrin also inhibits GABA-T but does so irreversibly. Valproate's multiple mechanisms of action explain its broad-spectrum efficacy against absence, myoclonic, tonic-clonic, and partial seizures. Its teratogenicity (neural tube defects) necessitates folic acid supplementation.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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