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  • Title: Mechanism of gastroprokinetic effect of EM523, an erythromycin derivative, in dogs.
    Author: Ohtawa M, Mizumoto A, Hayashi N, Yanagida K, Itoh Z, Omura S.
    Journal: Gastroenterology; 1993 May; 104(5):1320-7. PubMed ID: 8482446.
    Abstract:
    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 micrograms/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.
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