(+)-U-50488 hydrochloride

(+)-U-50488 hydrochloride是一种作用于κ阿片受体的选择性激动剂[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.

(+)-U-50488 hydrochloride是一种选择性的KOR激动剂[1].在离体大鼠DRG神经元中,U-50488(0.340 μM)抑制电压非依赖性Ca2+通道电流.在不表达KOR的HeLa细胞中,U-50488(20 μM)阻断Ca2+通道[2].

在恒河猴中,U-50488显示出强效的镇痛作用并产生利尿作用[1].U-50488增强电诱导的兔输精管收缩,IC50值为26.5 nM.在小鼠中,U-50488损害运动功能, ED50值为15.3 mg/kg,并降低自发性活动[3].在成年大鼠中,U-50488增加保持自我刺激响应(抑郁样效果)所需要的阈值.同时,男性对阈值增加的效应比女性更加敏感[4].

参考文献：
[1].  Tang AH, Collins RJ. Behavioral effects of a novel kappa opioid analgesic, U-50488, in rats and rhesus monkeys. Psychopharmacology (Berl), 1985, 85(3): 309-314.
[2].  Hassan B, Ruiz-Velasco V. The κ-opioid receptor agonist U-50488 blocks Ca2+ channels in a voltage- and G protein-independent manner in sensory neurons. Reg Anesth Pain Med, 2013, 38(1): 21-27.
[3].  Lu SN, Ma SC, Zhang KG, et al. Comparison of pharmacological profile of selective kappa-opioid agonist K-II and U-50488. Yao Xue Xue Bao, 1991, 26(3): 171-174.
[4].  Russell SE, Rachlin AB, Smith KL, et al. Sex differences in sensitivity to the depressive-like effects of the kappa opioid receptor agonist U-50488 in rats. Biol Psychiatry, 2014, 76(3): 213-222.