RESPONSES OF ISOLATED DOG SMALL INTESTINE TO ANALGESIC AGENTS

¹ Department of Pharmacology, College of Medicine, University of Iowa, Iowa City, Iowa

Previous work has shown that morphine and related analgesic agents enhance release of 5-hydroxytryptamine (5-HT) into solution perfusing dog intestinal vasculature while stimulating the intestinal sections to produce contractions of the smooth muscle. In order to determine whether the amount of 5-HT released by analgesics is related to the doses of the drugs employed, various analgesic agents were studied in isolated dog intestinal sections and their abilities to enhance smooth muscle tone and release 5-HT were compared. Release of 5-HT and intestinal stimulation by morphine, pentazocine and cyclazocine were found to be doserelated; cyclazocine and pentazocine were shown to be less potent than morphine as releasers of 5-HT and as intestinal stimulants. The d-isomer of racemorphan (Dromoran) was less potent than its l-isomer as a releaser of 5-HT and as a gut stimulant; the d-and l-isomers of methadone could not be shown to differ in potency. These data provide evidence that the release of 5-HT from the dog intestine is related to the dose of analgesic employed and that there exists stereospecificity of this response.