Effects of aspirin and paracetamol on naloxone reversal of morphine-induced inhibition of gastrointestinal propulsion in mice.
In mice, morphine caused a dose-dependent slowing of the rate of intestinal transit of a charcoal meal. This inhibitory effect of morphine was antagonised by naloxone. Pretreatment with a single dose of morphine did not induce any detectable tolerance to the inhibitory action of a second dose of morphine given 4 h later. However, naloxone was more effective in antagonising intestinal inhibition by morphine in morphine-pretreated mice than in saline-pretreated animals. Pretreatment with either aspirin or paracetamol did not alter the inhibitory action of morphine given 4.5 h later. However, the antagonistic effect of naloxone was significantly augmented, though not to the same extent as that caused by morphine pretreatment. When either aspirin or paracetamol was given together with morphine as pretreatment, the resulting naloxone antagonism measured 4 h later was significantly higher than that induced by pretreatment with the individual drugs. Furthermore, combined pretreatment with aspirin 20.0 mg/kg and morphine 40.0 mg/kg induced detectable tolerance to the inhibitory effect of a second dose of morphine given 4 h later. The present study indicates that prostaglandins reduce the naloxone antagonism of the inhibitory action of morphine on the rate of intestinal transit in mice and may interfere with the development of morphine tolerance.
D000082:Acetaminophen / Q000494:pharmacology*; D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D004361:Drug Tolerance; D005769:Gastrointestinal Motility / Q000187:drug effects*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000037:antagonists & inhibitors*; D009270:Naloxone / Q000494:pharmacology*; D011453:Prostaglandins / Q000502:physiology
D011453:Prostaglandins; D000082:Acetaminophen; D009270:Naloxone; D009020:Morphine; D001241:Aspirin