Brexpiprazole

Brexpiprazole是一种有效的5-HT2A\α1B-和α2C-肾上腺素能受体拮抗剂,同时也是血清素1A(5-HT1A)与D2受体的部分激动剂[1].

5-HT1A受体属于G蛋白偶联受体,可以结合内源性神经递质血清素5-HT以介导抑制性神经传递.D2受体也属G蛋白偶联受体,能够抑制腺苷酸环化酶活性.

在克隆受体系统中,Brexpiprazole对h5-HT1A和hD2受体具有部分激动效应,同时有效地拮抗h5-HT2A受体和hα1B/2C肾上腺素能受体[2].在PC12细胞中,Brexpiprazole作用于5-HT1A受体和5-HT2A受体,从而呈浓度依赖性地增加具有神经突的细胞数量[3].

在Dizocilpine诱导的社会认知障碍小鼠模型中,Brexpiprazole(0.01\0.03和0.1 mg/kg,口服)显著改善认知障碍,对未经处理的对照组小鼠则没有影响.Brexpiprazole有望用于治疗精神疾病患者的社会认知障碍[1].

参考文献：
[1].  Noriko Yoshimi, Takashi Futamura, Kenji Hashimoto. Improvement of dizocilpine-induced social recognition deficits in mice by brexpiprazole, a novel serotonin-dopamine activity modulator. European Neuropsychopharmacology, http://dx.doi.org/10.1016/j.euroneuro.2014.12.014
[2].  Maeda K, Sugino H, Akazawa H et al. Brexpiprazole I: in vitro and in vivo characterization of a novel serotonin-dopamine activity modulator. journal of pharmacology and experimental therapeutics, 2014 Sep;350(3):589-604.
[3].  Tamaki Ishima, Takashi Futamura, Yuta Ohgi et al. Potentiation of neurite outgrowth by brexpiprazole, a novel serotonin–dopamine activity modulator: A role for serotonin 5-HT1A and 5-HT2A receptors. European Neuropsychopharmacology, http://dx.doi.org/10.1016/j.euroneuro.2015.01.014