Benzodiazepine mechanism — MRCPsych Paper A MCQ

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EasyPsychopharmacologyBenzodiazepine mechanismMRCPsych Paper A

A 52-year-old man with alcohol dependence develops tremor, anxiety and autonomic hyperactivity after abruptly stopping alcohol. He is given diazepam. Which molecular action best explains the therapeutic effect of diazepam?

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Correct answer: E — Positive allosteric modulation of GABA-A receptors

Diazepam is a benzodiazepine that acts as a positive allosteric modulator at benzodiazepine-sensitive GABA-A receptors. It does not directly activate the receptor in the absence of GABA; instead, it enhances GABA-mediated opening of the receptor's chloride channel, increasing neuronal inhibition and reducing the central hyperexcitability of alcohol withdrawal. Therefore, E is correct. 5-HT1A agonism is associated with buspirone. Voltage-gated sodium-channel blockade is characteristic of drugs such as carbamazepine and lamotrigine. Dopamine-reuptake inhibition is a stimulant mechanism, while NMDA-receptor antagonism is associated with agents such as ketamine rather than diazepam.

Reference: Sigel E, Lüscher BP. A closer look at the high affinity benzodiazepine binding site on GABAA receptors. Current Topics in Medicinal Chemistry. 2011;11(2):241–246. https://pubmed.ncbi.nlm.nih.gov/21189125/