Which pharmacological property best explains why aripiprazole carries a very low risk of hyperprolactinaemia and minimal weight gain compared with risperidone and olanzapine?

• A Partial agonism at D2 receptors producing functional antagonism ✓
• B High affinity 5-HT2A antagonism
• C Irreversible binding to D2 receptors
• D Selective D4 receptor antagonism

Explanation

Aripiprazole is a partial agonist at D2 receptors with high intrinsic stability. In hyperdopaminergic mesolimbic states it acts as a functional antagonist, while in the tuberoinfundibular pathway its partial agonist activity maintains enough D2 stimulation to prevent sustained prolactin rise, unlike the full D2 blockade produced by risperidone. Its modest H1 and 5-HT2C affinity explains the lower weight gain than olanzapine, making option B the tempting but incorrect distractor.

Reference: Katzung's Basic and Clinical Pharmacology, 16th ed.

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