Lahti R A, VonVoigtlander P F, Barsuhn C
Life Sci. 1982;31(20-21):2257-60. doi: 10.1016/0024-3205(82)90132-1.
U-50,488H has been shown to be a naloxone antagonizable analgesic in rodents. However, the dose of naloxone needed for antagonism is higher than it is for morphine. U-50,488H does not produce physical dependence; however it does produce tolerance upon chronic administration. U-50,488H is cross tolerant with bremazocine but not with morphine. Monkeys trained to discriminate ethylketocyclazocine (EKC) from saline show a complete generalization to U-50,488H but not to morphine. The evaluation of U-50,488H in 3H-EKC site-selective binding indicated that U-50,488H has a high affinity for the kappa receptor (Ki = 114 nM) and a low affinity for the mu receptor (Ki = 6100 nM). The ratio of Ku/Kk was 0.08 for morphine, 0.4 for dynorphin, and 53.5 for U-50,488H. The data suggest that U-50,488H is a selective agonist at the opioid kappa receptor.
U - 50,488H已被证明在啮齿动物中是一种可被纳洛酮拮抗的镇痛药。然而，拮抗所需的纳洛酮剂量高于吗啡。U - 50,488H不会产生身体依赖性；但长期给药会产生耐受性。U - 50,488H与布马佐辛有交叉耐受性，但与吗啡没有。经过训练能区分乙基酮环唑辛（EKC）和生理盐水的猴子对U - 50,488H表现出完全的泛化反应，但对吗啡没有。对U - 50,488H进行的3H - EKC位点选择性结合评估表明，U - 50,488H对κ受体具有高亲和力（Ki = 114 nM），对μ受体具有低亲和力（Ki = 6100 nM）。吗啡的Ku/Kk比值为0.08，强啡肽为0.4，U - 50,488H为53.5。数据表明U - 50,488H是阿片类κ受体的选择性激动剂。
