[Effect of motilin agonist, EM-523 on gastrointestinal motility]

Abstract

In this study, we investigated the effect of EM-523, one of the erythromycin derivatives, on gastrointestinal motility in conscious dogs, in which force transducers were chronically implanted in the gastrointestinal tract. As a result, intravenous administration of EM-523 (1-10 micrograms/kg) induced phase III-like contractions in the stomach, and the EM-523-induced contractions migrated along the entire small intestine. EM-523 also stimulated the lower esophageal sphincter and the gallbladder motility, quite similar to exogenous motilin. Furthermore, we have investigated the effects of EM-523 both in postoperative ileus dogs and truncally vagotomized dogs. The dogs 1 to 4-day after the operation showed continuous and irregular contractions in the entire gastrointestinal tract, instead of typical interdigestive contractions. In these conditions, EM-523 induced strong phasic contractions in the stomach and duodenum, although these contractions did not always migrate along the small intestine. In the vagotomized dogs, spontaneous phase III contractions tended to be weaker than those in the normal dogs. EM523 induced phase III-like contractions in vagotomized dogs as in the normal dogs, and the contractile activities were improved. These results indicated that EM-523 may be useful as a gastroprokinetic drug for postoperative ileus and the patients with vagotomy.