Brexpiprazole is a novel D2 dopamine and serotonin 1A partial agonist, called serotonin-dopamine activity modulator (SDAM), and a potent antagonist of serotonin 2A receptors, noradrenergic alpha 1B and 2C receptors.
信号通路
Neuronal Signaling; GPCR & G Protein
靶点
5-HT1A
human noradrenergic α1B
Dopamine D2L
5-HT2A receptors
α2C receptors
IC50
0.12nM(Ki)
0.17nM(Ki)
0.3nM(Ki)
0.47nM(Ki)
0.59nM(Ki)
体外研究
Brexpiprazole is a potent partial agonist at human 5-hydroxytryptamine (5-HT) 5-HT1A (Ki=0.12nM) and dopamine D2L (Ki=0.3nM) receptors, and an antagonist at 5-HT2A receptors (Ki=0.47nM). It also shows potent antagonist activity at human noradrenergic α1B (Ki=0.17nM) and α2Creceptors (Ki=0.59nM). Furthermore, this drug displays moderate affinity for human D3, 5-HT2B and 5-HT7 receptors, as well as α1A, and α1D adrenergic receptors. Brexpiprazole potentiatedngF-induced neurite outgrowth in PC12 cells. It could significantly potentiate the effects of fluoxetine (or paroxetine) on neurite outgrowth.
体内研究
Brexpiprazole is able to ameliorate PCP-191 induced cognitive deficits in mice, via 5-HT1A receptors.
临床实验
N/A
特征
N/A
相关实验数据(此数据来自于公开文献,碧云天并不保证其有效性):
酶活性检测实验
方法
N/A
细胞实验
细胞系
PC12 cells
浓度
0.001,0.01,0.1或1.0μM
处理时间
4 days
方法
2.5ng/ml of ngF (nerve growth factor) is used to study the potentiating effects of brexpiprazole on neurite outgrowth. Twenty-four hours after plating, the medium is replaced with DMEM medium containing 0.5% FBS and 1% penicillin-streptomycin withngF (2.5ng/ml), with or without brexpiprazole (0.001, 0.01, 0.1 or 1.0μM). Four days after incubation withngF (2.5ng/ml) with or without drugs, morphometric analysis is performed on digitized images of live cells taken under phase-contrast illumination, with an inverted microscope linked to a camera.
动物实验
动物模型
Male ICR mice
配制
0.5% methylcellulose
剂量
0.3, 1, or 3mg/kg/day
给药方式
oral administration
参考文献: 1. Ishima T, et al. Eur Neuropsychopharmacol. 2015, 25(4):505-511.
2. Yoshimi N, et al. Pharmacol Biochem Behav. 2014, 124:245-249.
包装清单: