Brexpiprazole, approved for adjunctive treatment of major depression and schizophrenia, differs from aripiprazole at the D2 receptor in which pharmacologically important way?

• A Brexpiprazole is a full D2 agonist whereas aripiprazole is a partial agonist
• B Brexpiprazole is a D2 inverse agonist unlike the D2 partial agonism of aripiprazole
• C Brexpiprazole antagonises D2 completely with no intrinsic activity
• D Brexpiprazole has lower intrinsic activity (partial agonism) at D2 compared to aripiprazole ✓

Explanation

Both aripiprazole and brexpiprazole are D2 partial agonists (dopamine system stabilisers), but brexpiprazole has even lower intrinsic activity (efficacy) at D2 receptors compared to aripiprazole. This produces less dopaminergic activation at times of low endogenous dopamine, contributing to its better tolerability profile with lower risk of activation, restlessness, and insomnia compared to aripiprazole. Brexpiprazole also has higher affinity for serotonin 1A and 2A receptors. It is not a full agonist, inverse agonist, or pure antagonist at D2.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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