生物活性

• 靶点

  Dopamine Receptor D3 Ki:0.09nM

  Dopamine Receptor D2 Ki:0.5nM

  5-HT Receptor 1A Ki:2.6nM

• 描述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. Cariprazine occupied D(2)/D(3) receptors in a dose-dependent and saturable manner, with the lowest dose occupying ~5% of receptors and the highest dose showing more than 90% occupancy^[3]. Cariprazine demonstrated approximately 10-fold higher affinity for human D(3) versus human D(2L) and human D(2S) receptors (pKi 10.07, 9.16, and 9.31, respectively). 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 is related to these receptors^[4]. Cariprazine pretreatment significantly attenuated the emergence of these cognitive deficits in PCP-treated (phencyclidine) wild-type mice, but not in PCP-treated D(3)-receptor knockout mice^[5]. Cariprazine was generally well tolerated in clinical trials, with most adverse events being of mild to moderate severity, and metabolic changes observed were considered generally not clinically significant. Cariprazine is a useful addition to the treatment options for schizophrenia, and may be of particular use in patients with predominantly negative symptoms^[6].