Naloxone reversal of drug-induced diarrhea in mice.
The potential role of endogenous opiates in the mediation of the diarrheal actions of prostaglandin-F2 alpha (PGF2 alpha), 5-hydroxytryptophan (5-HTP) and methacholine was investigated. The interaction of the antidiarrheal agents morphine, propantheline bromide and cyproheptadine on the course of PGF2 alpha-induced diarrhea in mice was studied, as were the effects of naloxone on PGF2 alpha-, methacholine-, and 5-hydroxytryptophan-induced diarrhea. The three diarrheal agents, administered intraperitoneally, showed dose-dependent and parallel dose-response curves with the following order of decreasing potency: PGF2 alpha, methacholine and 5-HTP. Naloxone significantly inhibited the diarrhea induced by these agents. The diarrheal action of PGF2 alpha was also significantly attenuated with morphine, propantheline and cyproheptadine. These results suggest that PGF2 alpha, methacholine and 5-HTP induce diarrhea via a common pharmacological mechanism(s) which may involve an interaction with endogenous opiate receptors. However, the antagonism of diarrhea with agents having diverse pharmacological actions would suggest that factors unrelated to an interaction with endogenous opiates may also be involved in the production of diarrhea by the diarrheagenic agents studied.
D006916:5-Hydroxytryptophan / Q000037:antagonists & inhibitors; D000818:Animals; D000930:Antidiarrheals; D003533:Cyproheptadine / Q000494:pharmacology; D003967:Diarrhea / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D008297:Male; D008688:Methacholine Compounds / Q000037:antagonists & inhibitors; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology*; D011413:Propantheline / Q000494:pharmacology; D011460:Prostaglandins F / Q000037:antagonists & inhibitors
D000930:Antidiarrheals; D008688:Methacholine Compounds; D011460:Prostaglandins F; D011413:Propantheline; D003533:Cyproheptadine; D009270:Naloxone; D009020:Morphine; D006916:5-Hydroxytryptophan