Wong C L
Methods Find Exp Clin Pharmacol. 1984 Nov;6(11):685-9.
In the present study, the effects of morphine, a predominant mu-receptor agonist, and nalbuphine, a partial agonist supposedly acting on x-receptors, on intestinal motility were studied. The intestinal motility was measured by the transit of charcoal meal through the small intestine in mice. Morphine caused a dose-dependent slowing of the rate of intestinal transit in mice. This inhibitory effect of morphine was antagonised by naloxone administration. Nalbuphine also caused a dose-dependent inhibition of intestinal motility; the inhibition was less and showed a low-level plateau response, with a maximum of 40% inhibition. The effect of nalbuphine was antagonised by naloxone, but the antagonism was far less than that against morphine. Pretreatment with a single dose of morphine did not induce any change in the inhibitory effect of a second dose of morphine given four hours later. However, naloxone was more effective in antagonising the inhibitory effect of morphine in morphine-pretreated mice than in saline-pretreated animals. Pretreatment with morphine did not affect the inhibitory effect of nalbuphine, and the antagonistic potency of naloxone against nalbuphine was only marginally enhanced. Pretreatment with nalbuphine failed to alter the inhibitory effect of morphine as well as that of nalbuphine. Furthermore, nalbuphine pretreatment also had no effect on the antagonistic potency of naloxone against the inhibitory effects of nalbuphine and morphine on intestinal transit. These findings suggest that x-receptors are not important in the inhibitory effects of narcotic analgesics on intestinal transit and that a mu-receptor agonist is more effective in inducing enhancement of the antagonistic effect of naloxone.
在本研究中，研究了主要的μ受体激动剂吗啡和据推测作用于κ受体的部分激动剂纳布啡对肠道运动的影响。通过测定小鼠小肠中炭末的推进来测量肠道运动。吗啡使小鼠肠道推进速率呈剂量依赖性减慢。吗啡的这种抑制作用可被给予纳洛酮所拮抗。纳布啡也引起肠道运动的剂量依赖性抑制；这种抑制作用较小，呈现低水平的平台反应，最大抑制率为40%。纳布啡的作用可被纳洛酮拮抗，但拮抗作用远小于对吗啡的拮抗作用。单剂量吗啡预处理并未引起4小时后给予的第二剂吗啡的抑制作用发生任何变化。然而，纳洛酮在拮抗吗啡预处理小鼠中吗啡的抑制作用方面比在生理盐水预处理动物中更有效。吗啡预处理不影响纳布啡的抑制作用，且纳洛酮对纳布啡的拮抗效力仅略有增强。纳布啡预处理未能改变吗啡以及纳布啡的抑制作用。此外，纳布啡预处理对纳洛酮拮抗纳布啡和吗啡对肠道推进的抑制作用的拮抗效力也没有影响。这些发现表明，κ受体在麻醉性镇痛药对肠道推进的抑制作用中并不重要，且μ受体激动剂在诱导增强纳洛酮的拮抗作用方面更有效。
