Comparison of the motor-stimulating action of EM523, an erythromycin derivative, and prostaglandin F2 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 F2 alpha (PGF2 alpha). EM523 and motilin given as i.v. infusions induced strong contractions in the stomach that migrated along the intestine. On the other hand, PGF2 alpha stimulated intestinal contractions, but its effect on gastric motility was weak. EM523 had 1/50 the potency of motilin and 6 times the potency of PGF2 alpha for stimulation of intestinal motility. Atropine at 0.1 mg/kg, i.v. strongly inhibited gastrointestinal contractions induced by EM52 EM523 or motilin and partly inhibited PGF2 alpha-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 PGF2 alpha. Infusion of EM523 at 100 micrograms/kg/hr induced strong migrating contractions even when motility was depressed by dopamine infusion or laparotomy. Infusion of PGF2 alpha at 300 micrograms/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 PGF2 alpha-induced intestinal contractions.