Which drug is a partial agonist at D2 and D3 with high affinity for 5-HT1A?

Which drug is a partial agonist at D2 and D3 with high affinity for 5-HT1A?

• A. Cariprazine
• B. Brexpiprazole
• C. Aripiprazole
• D. Ziprasidone

Answer: (A)

Partial agonism at dopamine D2 receptors, with even more emphasis on D3, paired with 5-HT1A partial agonism, is a distinctive pharmacologic profile. This combination allows modulation of both dopaminergic and serotonergic systems, which can help reduce positive symptoms while potentially improving negative symptoms and cognitive aspects, and can provide anxiolytic/antidepressant–like effects. Cariprazine fits this profile best because it is a dopamine D2/D3 partial agonist with a strong preference for D3 receptors, and it also acts as a high-affinity 5-HT1A partial agonist. This D3 bias sets it apart from others on the list and aligns with the described mechanism. Brexpiprazole is also a D2 partial agonist with 5-HT1A partial agonism, but it has less D3 activity. Aripiprazole has D2 partial agonism with some D3 activity and 5-HT1A partial agonism as well, but its D3 affinity is not as pronounced as cariprazine. Ziprasidone largely behaves as a D2 antagonist with 5-HT2A antagonism and 5-HT1A agonism (not a partial agonist at D2/D3), so it doesn’t fit the given profile as well.

Partial agonism at dopamine D2 receptors, with even more emphasis on D3, paired with 5-HT1A partial agonism, is a distinctive pharmacologic profile. This combination allows modulation of both dopaminergic and serotonergic systems, which can help reduce positive symptoms while potentially improving negative symptoms and cognitive aspects, and can provide anxiolytic/antidepressant–like effects.

Cariprazine fits this profile best because it is a dopamine D2/D3 partial agonist with a strong preference for D3 receptors, and it also acts as a high-affinity 5-HT1A partial agonist. This D3 bias sets it apart from others on the list and aligns with the described mechanism.

Brexpiprazole is also a D2 partial agonist with 5-HT1A partial agonism, but it has less D3 activity. Aripiprazole has D2 partial agonism with some D3 activity and 5-HT1A partial agonism as well, but its D3 affinity is not as pronounced as cariprazine. Ziprasidone largely behaves as a D2 antagonist with 5-HT2A antagonism and 5-HT1A agonism (not a partial agonist at D2/D3), so it doesn’t fit the given profile as well.