A 29-year-old woman with schizophrenia needs an antipsychotic switch because of symptomatic hyperprolactinemia on risperidone. Her physician chooses aripiprazole. Which pharmacological property explains both its low propensity to raise prolactin and its low risk of metabolic side effects?

• A Partial agonism at D2 receptors ✓
• B High affinity antagonism at 5-HT2A receptors
• C Irreversible blockade of D2 receptors
• D Selective antagonism at D4 receptors

Explanation

Aripiprazole is a partial agonist at D2 receptors, so it stabilizes dopaminergic tone: it dampens excess mesolimbic activity while providing modest intrinsic activity in the tuberoinfundibular pathway, which prevents prolactin elevation. Its minimal H1 and 5-HT2C antagonism accounts for the low weight gain and diabetes risk compared with olanzapine and clozapine. Pure D2 antagonists such as risperidone disinhibit prolactin release, and no clinically used antipsychotic is a selective D4 antagonist.

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

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