The effects of morphine and nalbuphine on intestinal transit in mice.

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.