The effect of aspirin and paracetamol on the increased naloxone potency induced by morphine pretreatment.
Using the abdominal constriction test in mice, it was shown that pretreatment with a single dose of morphine given 3 h previously caused a marked increase in the antagonistic effect of naloxone without any change in the antinociceptive action of morphine itself. Pretreatment with either paracetamol (10.0-20.0 mg/kg, s.c.) or aspirin (5.0-10.0 mg/kg, s.c.) caused a small but significant antagonism of the antinociceptive effect of morphine, while the antagonistic action of naloxone remained unaffected. However, when aspirin or paracetamol was administered with morphine in the pretreatment regime, the ability of morphine to induce an increase in naloxone potency was much attenuated. This inhibitory effect was dependent on the dose of aspirin or paracetamol used in the pretreatment regime. The antinociceptive effect of aspirin and paracetamol was also studied. In the doses used, they did have a mild antinociceptive effect, but the analgesic effect of morphine was not affected by the administration of these drugs 30 min beforehand. It is suggested that the antinociceptive effect of morphine is probably not dependent on prostaglandin, but that the induction of increased naloxone potency is likely to be mediated through prostaglandin synthesis.
D000082:Acetaminophen / Q000494:pharmacology*; D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D051379:Mice; D009020:Morphine / Q000037:antagonists & inhibitors*; D009270:Naloxone / Q000494:pharmacology*; D009619:Nociceptors / Q000187:drug effects; D011453:Prostaglandins / Q000096:biosynthesis
D011453:Prostaglandins; D000082:Acetaminophen; D009270:Naloxone; D009020:Morphine; D001241:Aspirin