Comparison Of The Motor-Stimulating Action Of Em523, An Erythromycin Derivative, And Prostaglandin-F(2-Alpha) In Conscious Dogs

The effect of EM523 [de(N-methyl)-N-ethyl-8,9-anhydroerythromycin A 6,9-hemiacetal], an erythromycin derivative, on gastrointestinal motility was investigated using conscious dogs in the fasting state, and it was compared with those of motilin and prostaglandin F2alpha (PGF2alpha). EM523 and motilin given as i.v. infusions induced strong contractions in the stomach that migrated along the intestine. On the other hand, PGF2alpha stimulated intestinal contractions, but its effect on gastric motility was weak. EM523 had 1150 the potency of motilin and 6 times the potency of PGF2alpha for stimulation of intestinal motility. Atropine at 0.1 mg/kg, i.v. strongly inhibited gastrointestinal contractions induced by EM523 or motilin and partly inhibited PGF2alpha-induced intestinal motility. ICS-205-930, a 5HT3-receptor antagonist, at a dose of 1 mg/kg, i.v. strongly inhibited EM523 or motilin-induced gastric contractions but did not affect the action of PGF2alpha. Infusion of EM523 at 100 mug/kg/hr induced strong migrating contractions even when motility was depressed by dopamine infusion or laparotomy. Infusion of PGF2alpha at 300 mug/kg/hr stimulated intestinal but not gastric motility under these conditions. The results of this study indicate that the cholinergic pathway and 5HT3 receptors are involved in EM523 and motilin-induced migrating gastrointestinal contractions, whereas the cholinergic pathway seems to be only partly involved in PGF2alpha-induced intestinal contractions.