BRL 52537 hydrochloride

BRL 52537 hydrochloride是一种强效的和选择性的κ/μ阿片受体激动剂,作用于κ阿片受体的Ki值为0.24 nM [1].

κ阿片受体(KOR)是一类针对阿片肽强啡肽的阿片受体,控制成瘾.此外,KOR在紧张\焦虑\快感缺乏\抑郁症和增加药物寻求行为中起重要作用.

BRL 52537 hydrochloride是一种强效的和选择性的κ/μ阿片受体激动剂.在小鼠甩尾模型中,BRL 52537显示镇痛作用,ED50值为0.05 mg/kg,比吗啡效力强25倍[1].在大脑中动脉闭塞WT雄性小鼠中,再灌注72小时时,BRL 52537显著减少梗死体积.然而,BRL 52537对神经元NO合酶无效突变体(nNOS-/-)小鼠或WT雌性小鼠没有影响.这些结果表明,BRL 52537通过抑制缺血诱发的NO产生和nNOS活性,表现出神经保护作用[2].在成年大鼠背根神经节(DRGs)中,BRL 52537以阿片受体非依赖的方式抑制抗河豚毒素(TTX-R)钠电流,这也有助于其镇痛作用[3].在脑缺血/再灌注(I/R)损伤大鼠中,BRL52537抑制神经细胞凋亡和脑损伤.此外,BRL52537增加磷酸化STAT3的水平并减少caspase-3表达[4].

参考文献：
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[2].  Zeynalov E, Nemoto M, Hurn PD, et al. Neuroprotective effect of selective kappa opioid receptor agonist is gender specific and linked to reduced neuronal nitric oxide. J Cereb Blood Flow Metab, 2006, 26(3): 414-420.
[3].  Su X, Castle NA, Antonio B, et al. The effect of kappa-opioid receptor agonists on tetrodotoxin-resistant sodium channels in primary sensory neurons. Anesth Analg, 2009, 109(2): 632-640.
[4].  Fang S, Xu H, Lu J, et al. Neuroprotection by the kappa-opioid receptor agonist, BRL52537, is mediated via up-regulating phosphorylated signal transducer and activator of transcription-3 in cerebral ischemia/reperfusion injury in rats. Neurochem Res, 2013, 38(11): 2305-2312.