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The effects of morphine and nalbuphine on intestinal transit in mice
Abstract:
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.
Insights
Morphine and nalbuphine slow intestinal transit in mice. Naloxone effectively blocks morphine
Area of Science:
- Pharmacology
- Gastroenterology
- Neuroscience
Background:
- Opioid analgesics, like morphine, are known to affect gastrointestinal motility.
- The specific receptor interactions and effects of different opioid agonists and antagonists on intestinal transit require further elucidation.
Purpose of the Study:
- To investigate the effects of morphine (mu-receptor agonist) and nalbuphine (supposed kappa-receptor agonist) on mouse intestinal motility.
- To determine the role of mu- and kappa-receptors in mediating these effects and the interaction with naloxone.
Main Methods:
- Intestinal motility was assessed in mice using the charcoal meal transit method.
- Dose-dependent effects of morphine and nalbuphine were evaluated.
- The antagonistic effects of naloxone were studied, including in pretreated animals.
Main Results:
- Morphine produced a dose-dependent inhibition of intestinal transit, which was antagonized by naloxone.
- Nalbuphine also inhibited transit in a dose-dependent manner, but with a lesser maximal effect (40%) and weaker naloxone antagonism.
- Pretreatment with morphine enhanced naloxone's antagonism of morphine but not nalbuphine's effects.
Conclusions:
- Kappa-receptors appear not to be significantly involved in the inhibitory effects of narcotic analgesics on intestinal transit.
- Mu-receptor agonists are more effective in enhancing the antagonistic action of naloxone on intestinal motility.