Cariprazine(RGH188)盐酸盐有抗精神病活性，对D3和D2受体有较高亲和力，Ki分别为0.09 nM和0.5 nM，对5-HT(1A)受体有一定亲和力。
Description:IC50 Value: 0.5 and 0.09 nM (Ki for D2 and D3 receptor respectively); 2.6 and 180 nM(Ki for 5-HT1A and 5-HT2A receptor respectively)
Cariprazine is a novel antipsychotic drug candidate that exhibits high selectivity and affinity to dopamine D(3) and D(2) receptors and moderate affinity to serotonin 5-HT(1A) receptors.
in vitro: Cariprazine had lower affinity at human and rat hippocampal 5-HT(1A) receptors (pK(i) 8.59 and 8.34, respectively) and demonstrated low intrinsic efficacy.Cariprazine displayed low affinity at human 5-HT(2A) receptors (pK(i) 7.73). Moderate or low affinity for histamine H(1) and 5-HT(2C) receptors (pK(i) 7.63 and 6.87, respectively) suggest cariprazine’s reduced propensity for adverse events related to these receptors.
in vivo: Doses ≥ 1.5 mg/d yielded 69 – 75% D2/D3 receptor occupancy as measured in positron emission tomography scans. Mean half-life for cariprazine was 2 – 5 d over a dose range of 1.5 – 12.5 mg. Cariprazine, as well as aripiprazole and bifeprunox, were able to reduce the rewarding effect of cocaine (minimum effective doses were 0.17, 1, and 0.1 mg/kg, respectively) and attenuated relapse to cocaine seeking with half maximal effective dose [ED??] values of 0.2, 4.2, and 0.17 mg/kg, respectively.
Toxicity: In the fixed-dose study of cariprazine that tested 1.5, 3.0, and 4.5 mg/day, the most commonly encountered adverse events were insomnia, extrapyramidal disorder, sedation, akathisia, nausea, dizziness, vomiting, anxiety, and constipation.
Clinical trial: Cariprazine is in phase III clinical trials in patients with schizophrenia and in patients with bipolar disorder.