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 mind map of cariprazine can be summarized as follows:
- Mechanism of action: unknown, but may involve partial agonist activity at dopamine D2 and serotonin 5-HT1A receptors, and antagonist activity at serotonin 5-HT2A receptors
- Receptor binding profile:
- Partial agonist at dopamine D3 and D2 receptors
- Partial agonist at serotonin 5-HT1A receptors
- Antagonist at 5-HT2B and 5-HT2A receptors
- Binds to histamine H1 receptors
- Key points:
- Cariprazine has a unique receptor binding profile compared to other antipsychotics
- The exact mechanism of action is unknown, but may involve a combination of partial agonist and antagonist activities at various receptors 1
From the Research
Cariprazine is a dopamine D3- and D2-receptor partial agonist that is primarily used to treat schizophrenia and bipolar I disorder, with a recommended starting dose of 1.5 mg once daily, which can be increased to 3-6 mg daily based on response. The medication has a uniquely long half-life, meaning it takes longer to reach steady state and effects persist longer after discontinuation 2.
Key Points
- Cariprazine has been shown to be effective in treating schizophrenia, with a number needed to treat vs placebo for response of ten for the approved dose range of 1.5-6 mg/day 3.
- The medication has also been found to be effective for the maintenance treatment of schizophrenia, delaying time to relapse when compared with placebo (HR 0.45) 3.
- Cariprazine may be particularly beneficial for patients with predominant negative symptoms of schizophrenia due to its D3 receptor activity, which is thought to improve cognitive and negative symptoms 2.
- Common side effects include akathisia (restlessness), insomnia, headache, and weight gain, though the metabolic effects are generally less pronounced than with some other antipsychotics 3, 4.
- The medication should be used cautiously in patients with cardiovascular disease, and regular monitoring of metabolic parameters is recommended 4.
Dosage and Administration
- For schizophrenia, the typical dosing starts at 1.5 mg once daily, which can be increased to 3-6 mg daily based on response 3.
- For bipolar mania, treatment usually begins at 1.5 mg on day one, potentially increasing to 3-6 mg daily 5.
Special Considerations
- Cariprazine has a uniquely long half-life (2-4 days for the parent compound and up to 3 weeks for its active metabolite), meaning it takes longer to reach steady state and effects persist longer after discontinuation 2.
- The medication may be particularly beneficial for patients with predominant negative symptoms of schizophrenia due to its D3 receptor activity, which is thought to improve cognitive and negative symptoms 2.