Biological Receptors Targeted by Vraylar (Cariprazine)
Vraylar (cariprazine) acts as a partial agonist at dopamine D2 and D3 receptors (with preferential binding to D3 receptors) and serotonin 5-HT1A receptors, while functioning as an antagonist at serotonin 5-HT2A and 5-HT2B receptors. 1
Primary Receptor Targets
Dopamine Receptors
- D3 receptors: Cariprazine binds with very high affinity (Ki = 0.085 nM) and acts as a partial agonist, showing preferential binding compared to D2 receptors 1, 2
- D2 receptors: Acts as a partial agonist with high binding affinity (Ki = 0.49 nM for D2L and 0.69 nM for D2S) 1
- The D3-preferring profile distinguishes cariprazine from most other antipsychotics 3, 4
Serotonin Receptors
- 5-HT1A receptors: Partial agonist activity with high binding affinity (Ki = 2.6 nM) 1, 3
- 5-HT2A receptors: Antagonist activity with moderate binding affinity (Ki = 18.8 nM) 1, 3
- 5-HT2B receptors: Antagonist activity with high binding affinity (Ki = 0.58 nM) 1, 4
- 5-HT2C receptors: Lower binding affinity (Ki = 134 nM) 1
Secondary Receptor Targets
Histamine and Adrenergic Receptors
- Histamine H1 receptors: Moderate binding affinity (Ki = 23.2 nM) 1, 4
- α1A-adrenergic receptors: Lower binding affinity (Ki = 155 nM) 1
Receptors with Minimal or No Affinity
- Cholinergic muscarinic receptors: No appreciable affinity (IC50 > 1000 nM) 1
Active Metabolites with Similar Receptor Profiles
Cariprazine forms two major active metabolites—desmethylcariprazine (DCAR) and didesmethylcariprazine (DDCAR)—that have in vitro receptor binding profiles similar to the parent drug and are pharmacologically equipotent to cariprazine 1, 3. DDCAR has a substantially longer half-life (1-3 weeks) compared to cariprazine (2-4 days), with systemic exposure to DDCAR being approximately 400% of cariprazine concentrations by the end of 12-week treatment 1, 5.
Clinical Significance of Receptor Profile
The unique receptor binding profile—particularly the D3 preferential binding and partial agonist activity at D2/D3 receptors combined with 5-HT1A partial agonism and 5-HT2A antagonism—is thought to mediate cariprazine's efficacy in treating both positive and negative symptoms of schizophrenia and bipolar disorder 1, 2. This profile may also explain the relatively favorable metabolic profile compared to some other atypical antipsychotics, as cariprazine has no clinically meaningful alterations in metabolic variables 3.