Aripiprazole mechanism — MRCPsych Paper A MCQ

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ModeratePsychopharmacologyAripiprazole mechanismMRCPsych Paper A

A 32-year-old man with schizophrenia develops clinically significant weight gain while taking olanzapine and is switched to aripiprazole. Which receptor action most characteristically distinguishes aripiprazole from conventional dopamine-blocking antipsychotics?

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Correct answer: C — Partial agonism at dopamine D2 receptors

Aripiprazole is distinguished by partial agonism at dopamine D2 receptors. A partial agonist has lower intrinsic activity than dopamine and can therefore reduce signalling when dopaminergic activity is high while retaining some receptor activation when it is low. Its broader pharmacology also includes partial agonism at 5-HT1A receptors and antagonism at 5-HT2A receptors. It is not an irreversible D2 antagonist; antipsychotic D2 binding is generally reversible. Muscarinic M1 blockade contributes to anticholinergic adverse effects but is not aripiprazole's defining mechanism. Vesicular monoamine transporter inhibition is associated with monoamine-depleting or VMAT2-inhibiting drugs, while positive GABA-A modulation is characteristic of drugs such as benzodiazepines.

Reference: Electronic Medicines Compendium, Aripiprazole Milpharm 5 mg tablets, Summary of Product Characteristics, section 5.1 Pharmacodynamic properties, revised 2026. https://www.medicines.org.uk/emc/product/7073/smpc