From the FDA Drug Label
The mechanism of action of cariprazine is unknown. However, the efficacy of cariprazine could be mediated through a combination of partial agonist activity at central dopamine D2 and serotonin 5-HT1A receptors and antagonist activity at serotonin 5-HT2A receptors Cariprazine acts as a partial agonist at the dopamine D3 and D2 receptors with high binding affinity (Ki values 0.085 nM, and 0.49 nM (D2L) and 0. 69 nM (D2S), respectively) and at the serotonin 5-HT1A receptors (Ki value 2.6 nM). Cariprazine acts as an antagonist at 5-HT2B and 5-HT2A receptors with high and moderate binding affinity (Ki values 0.58 nM and 18.8 nM respectively)
The mechanism of action of Vraylar (cariprazine) is not fully understood, but it is believed to be mediated through a combination of:
- Partial agonist activity at dopamine D2 and serotonin 5-HT1A receptors
- Antagonist activity at serotonin 5-HT2A receptors 1
From the Research
Vraylar (cariprazine) works primarily as a partial agonist at dopamine D3 and D2 receptors, with higher affinity for D3 receptors, which distinguishes it from other atypical antipsychotics. This unique receptor profile is believed to contribute to its effectiveness in treating both schizophrenia and bipolar disorder, as evidenced by studies such as 2. The medication's preferential binding to D3 receptors, which are concentrated in brain regions associated with mood, motivation, and cognition, is thought to modulate dopamine transmission, potentially reducing psychotic symptoms while causing fewer extrapyramidal side effects than full dopamine antagonists.
Key Mechanisms of Action
- Partial agonist at dopamine D3 and D2 receptors
- Higher affinity for D3 receptors
- Partial agonist at serotonin 5-HT1A receptors
- Antagonist at 5-HT2A receptors
Clinical Implications
The clinical efficacy and tolerability of cariprazine have been demonstrated in several studies, including 3, 4, and 2, which show its effectiveness in improving symptoms of schizophrenia and bipolar disorder. Its long half-life (approximately 2-4 days) allows for once-daily dosing, with the active metabolite didesmethyl-cariprazine having an even longer half-life of 1-3 weeks, contributing to sustained therapeutic effects.
Comparison with Other Antipsychotics
Cariprazine differs from other atypical antipsychotics, such as aripiprazole, in terms of its dopamine D3 receptor selectivity, as noted in studies like 5 and 6. This distinction may offer advantages in treating certain patient populations, particularly those with predominantly negative symptoms of schizophrenia. However, further studies are needed to fully discern the distinguishing features of cariprazine from other antimanic agents and antipsychotics.