The gastrointestinal motor stimulating activity of erythromycin (EM) was studied in conscious dogs. It was found that a 20-min intravenous infusion of EM lactobionate at a dose of 50-100 micrograms (potency) X kg-1 X h-1 induced a group of strong contractions in the stomach and the duodenum, and the contractions migrated along the small intestine to the terminal ileum. The EM-induced contractions were quite similar to the naturally occurring interdigestive migrating contractions (IMC) in the gastrointestinal tract in frequency, contractile force, and duration of the contractions, migrating velocity, and accompanying peaks of plasma motilin concentration. The EM-induced contractions in the stomach were inhibited by feeding and intravenous infusion of pentagastrin (1.5 micrograms X kg-1 X h-1) but were not affected by secretin; these findings are identical to those found with the naturally occurring and motilin-induced contractions. Like motilin, EM stimulated motor activity only during the interdigestive state. We conclude that EM induces IMC associated with the release of endogenous motilin in the dog.

For clarification of the nature of the side effects of macrolide antibiotics on the gastrointestinal tract, the motor-stimulating activity of these agents was studied in unanesthetized dogs. The results showed that erythromycin and oleandomycin, the 14-membered macrolides with two side chain sugars combined at C3 and C5 in a glycosidic linkage in parallel, strongly stimulate gastrointestinal motor activity, an action accompanied by vomiting at large doses. On the other hand, leucomycin, acetylspiramycin, and tylosin, belonging to a 16-membered macrolide with two side chain sugars in series combined at C5 of the lactone ring, did not induce contractions of the gastrointestinal tract. Motor-stimulating activity by erythromycin and oleandomycin was greatly inhibited by atropine sulfate. These results point to structure-physiological activity relationships.

The relation between the chemical structure of commercially available macrolide antibiotics and their activity in inducing interdigestive migrating contractions (IMC) was studied in conscious dogs. It was found that the 14-membered macrolides erythromycin and oleandomycin are active in inducing IMC in the stomach in association with the endogenous release of motilin. These erythromycin- and oleandomycin-induced contractions in the stomach migrated through the small intestine in a caudad direction. Conversely, 16-membered macrolide antibiotics such as leucomycin, acetylspiramycin, and tylosin do not induce any contractions in the stomach or stimulate endogenous release of motilin. These findings suggest that the IMC-inducing activity in macrolides seems to be closely related to their chemical configuration, i.e., the structure of 14-membered macrolides with dimethylaminosugar (desosamine) bound at C-5 and neutralsugar at C-3 in glycosidic linkage in parallel is likely to be necessary for IMC-inducing activity. The mechanisms by which erythromycin and oleandomycin stimulate endogenous motilin release are not known.

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