Pregabalin mechanism — MRCPsych Paper A MCQ

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ModeratePsychopharmacologyPregabalin mechanismMRCPsych Paper A

A 41-year-old woman with generalised anxiety disorder cannot tolerate SSRI or SNRI treatment and starts pregabalin. She asks how its pharmacological action differs from that of benzodiazepines. Which molecular action best describes pregabalin?

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Correct answer: E — Binding to alpha-2-delta subunits of voltage-gated calcium channels

Pregabalin binds to the alpha-2-delta auxiliary subunit of presynaptic voltage-gated calcium channels in the central nervous system. This modulates calcium-dependent neurotransmitter release and reduces neuronal excitability. Although pregabalin is structurally related to GABA, it does not exert its principal effect by directly modulating GABA-A receptors. Positive allosteric modulation of GABA-A receptors describes benzodiazepines, making E the most plausible distractor. Serotonin-transporter inhibition describes SSRIs, while irreversible monoamine-oxidase inhibition describes traditional MAOIs. Partial dopamine D2/D3 agonism is associated with drugs such as aripiprazole. Pregabalin nevertheless carries clinically important dependence, misuse and withdrawal risks despite its non-benzodiazepine mechanism.

Reference: Pregabalin Zentiva 100 mg hard capsules, Summary of Product Characteristics, section 5.1 Pharmacodynamic properties, text revised 23 January 2026. https://www.medicines.org.uk/emc/product/7008/smpc