Glutamatergic Modulation — MRCPsych Paper B MCQ

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HardSubstance MisuseGlutamatergic ModulationMRCPsych Paper B

A 46-year-old man with alcohol dependence completes assisted withdrawal and starts acamprosate alongside an alcohol-focused psychological intervention. Which pharmacodynamic action best characterises acamprosate and distinguishes it from a benzodiazepine used during assisted withdrawal?

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Correct answer: B — Antagonism of excitatory glutamatergic transmission

Acamprosate is principally associated in psychiatric examinations with modulation of the glutamatergic system. The UK SmPC states that it may antagonise excitatory amino-acid neurotransmission, particularly glutamate, while also possibly stimulating inhibitory GABAergic transmission. Therefore, antagonism of excitatory glutamatergic transmission is the best answer. Option D is the most plausible distractor: although acamprosate may influence GABAergic activity, it is not a positive allosteric modulator at the GABA-A benzodiazepine site, unlike benzodiazepines used for assisted alcohol withdrawal. Dopamine D2, serotonin 5-HT2A and noradrenergic alpha-2 actions do not characterise acamprosate. Its precise molecular mechanism remains incompletely established, so it should not be presented as a selective NMDA-receptor antagonist.

Reference: Electronic Medicines Compendium, Acamprosate 333 mg Gastro-resistant Tablets, Summary of Product Characteristics, section 5.1 Pharmacodynamic properties, revised November 2025. https://www.medicines.org.uk/emc/product/2729/smpc