A 28-year-old woman with a seizure disorder is started on valproate. Which of the following best explains valproate's efficacy in absence seizures?

• A Selective inhibition of sodium channels in hippocampal pyramidal cells
• B Blockade of T-type calcium channels in thalamic relay neurons ✓
• C Enhancement of GABA-A receptor-mediated chloride influx
• D Antagonism of NMDA receptors in the thalamo-cortical circuit

Explanation

Valproate exerts multiple mechanisms including inhibition of T-type (low threshold) calcium channels in thalamic neurons, which disrupts the rhythmic burst firing that generates the 3 Hz spike-and-wave pattern of absence seizures. It also inhibits GABA transaminase and succinate semialdehyde dehydrogenase, elevating brain GABA levels. The T-channel block is considered central to its anti-absence efficacy.

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

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