MECHANISM OF GASTROPROKINETIC EFFECT OF EM523, AN ERYTHROMYCIN DERIVATIVE, IN DOGS

Background: The pharmacological properties of EM523, a nonpeptide motilin agonist, have not been well characterized. Methods: The prokinetic effect of EM523 on motor-stimulating activity in the stomach, duodenum, and jejunum in seventeen conscious dogs was studied using force transducers implanted long term. EM523 (0.3-10.0 μg/kg) and receptor antagonists were injected intravenously during the interdigestive state. Results: EM523 induced phase III-like contractions in a dose-dependent manner, and the contractions were inhibited dose dependently by pretreatment with cholinergic and 5-HT3 receptor antagonists and dopamine but not by adrenoceptor and opiate antagonists or methysergide. The plasma immunoreactive motilin level was increased after EM523 to 60% of the mean maximum value during the spontaneous phase III contractions. Pretreatment with anti-canine motilin serum inhibited EM523-induced contractions by 19.2% in the motor index, but the contractile pattern was not affected. Conclusions: EM-523-induced phase III-like contractions are brought about through the cholinergic neural pathway and 5-HT3 receptors, and endogenous motilin release is partially involved. © 1993.