Sodium valproate has multiple mechanisms; which of the following is considered its PRIMARY mechanism of action in seizure control?

• A Selective blockade of T-type voltage-gated calcium channels
• B Allosteric potentiation of GABAA receptor at the benzodiazepine site
• C Antagonism of NMDA glutamate receptors
• D Blockade of voltage-gated sodium channels in a use-dependent manner AND inhibition of GABA transaminase increasing brain GABA ✓

Explanation

Valproate is a 'broad spectrum' AED with multiple mechanisms: use-dependent Na+ channel blockade reduces repetitive neuronal firing; inhibition of GABA transaminase (and succinic semialdehyde dehydrogenase) elevates brain GABA levels; and there is some T-type Ca2+ channel blockade contributing to absence seizure control. T-type Ca2+ channel blockade is the primary mechanism of ethosuximide, not valproate. Benzodiazepines act at the GABA-A BZD site, and ketamine/memantine block NMDA receptors.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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