BD 1063 dihydrochloride

BD 1063 dihydrochloride是一种σ-1受体的拮抗剂,Ki值为9.15 nM [1].

σ受体是一类阿片受体.σ受体有σ-1和σ-2两种亚型.σ-1受体在刺激多巴胺释放和调控可卡因行为中起重要作用[2].

BD 1063 dihydrochloride是一种σ-1受体拮抗剂,作用于σ-1受体和σ-2受体的Ki值分别为9.15和449 nM.BD 1063剂量依赖性地减少氟哌啶醇和二邻甲苯基胍(DTG)诱导的肌张力障碍[1].

在小鼠中,BD1063抑制整个大脑\皮层和纹状体中可卡因诱导的fra-2和σ-1受体的上调[2].在小鼠中,BD1063显著抑制可卡因诱导的抽搐\致死和运动刺激作用[3].在两种过度饮酒大鼠模型中,BD-1063剂量依赖性地减少乙醇自身给药,并抑制伏隔核中σ-1受体的表达[4].在小鼠中,BD-1063剂量依赖性地逆转热(辐射热)痛觉过敏和炎性机械(爪压力).然而,BD-1063对σ1敲除(σ1-KO)小鼠的热痛觉过敏没有影响.这些结果表明,σ1受体在炎性痛觉过敏中起重要作用[5].

参考文献：
[1].  Matsumoto RR, Bowen WD, Tom MA, et al. Characterization of two novel sigma receptor ligands: antidystonic effects in rats suggest sigma receptor antagonism. Eur J Pharmacol, 1995, 280(3): 301-310.
[2].  Liu Y, Chen GD, Lerner MR, et al. Cocaine up-regulates Fra-2 and sigma-1 receptor gene and protein expression in brain regions involved in addiction and reward. J Pharmacol Exp Ther, 2005, 314(2): 770-779.
[3].  Matsumoto RR, McCracken KA, Friedman MJ, et al. Conformationally restricted analogs of BD1008 and an antisense oligodeoxynucleotide targeting sigma1 receptors produce anti-cocaine effects in mice. Eur J Pharmacol, 2001, 419(2-3): 163-174.
[4].  Sabino V, Cottone P, Zhao Y, et al. The sigma-receptor antagonist BD-1063 decreases ethanol intake and reinforcement in animal models of excessive drinking. Neuropsychopharmacology, 2009, 34(6): 1482-1493.
[5].  Tejada MA, Montilla-García A, Sánchez-Fernández C, et al. Sigma-1 receptor inhibition reverses acute inflammatory hyperalgesia in mice: role of peripheral sigma-1 receptors. Psychopharmacology (Berl), 2014, 231(19): 3855-3869.