Skingle M, Hayes A G, Tyers M B
Neuropeptides. 1985 Feb;5(4-6):433-6. doi: 10.1016/0143-4179(85)90047-2.
The effects of several mu and kappa opioid receptor agonists on urinary excretion were examined in the water-loaded rat. Mu agonists induced anti-diuresis whereas kappa agonists caused diuresis. Furthermore, high efficacy kappa agonists eg. U50, 488H and tifluadom, produced marked diuretic effects, whereas kappa partial agonists eg. nalorphine, produced low maximum diuresis. Compounds having activity at both mu and kappa receptors eg. ethylketocyclazocine(EKC) and MR2034, produced a biphasic effect, an initial anti-diuretic effect followed by a more sustained diuretic effect. The irreversible mu receptor antagonist, beta-funaltrexamine (beta-FNA) antagonized the anti-diuretic effects elicited by fentanyl, pentazocine and buprenorphine and the initial anti-diuretic effect induced by EKC but did not inhibit the diuretic effects induced by U50, 488H and EKC. Thus, the use of beta-FNA in the water-loaded rat provides us with a valuable in vivo test which differentiates both mixed and selective opioid receptor agonists.
在水负荷大鼠中研究了几种μ和κ阿片受体激动剂对尿排泄的影响。μ激动剂诱导抗利尿作用，而κ激动剂引起利尿作用。此外，高效能κ激动剂，例如U50、488H和替氟朵，产生显著的利尿作用，而κ部分激动剂，例如烯丙吗啡，产生的最大利尿作用较低。在μ和κ受体上均有活性的化合物，例如乙基酮环唑辛（EKC）和MR2034，产生双相效应，即最初的抗利尿作用之后是更持久的利尿作用。不可逆的μ受体拮抗剂β-芬太尼酰苯胺（β-FNA）拮抗了芬太尼、喷他佐辛和丁丙诺啡引起的抗利尿作用以及EKC诱导的最初抗利尿作用，但不抑制U50、488H和EKC诱导的利尿作用。因此，在水负荷大鼠中使用β-FNA为我们提供了一种有价值的体内试验，可区分混合性和选择性阿片受体激动剂。
