Dual Role of Mosapride Citrate Hydrate on the Gastric Emptying Evaluated by the Breath Test in Conscious Rats

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  • Uchida Masayuki
    Food Science Institute, Division of Research and Development, Meiji Co., Ltd., Japan
  • Yamato Shigeru
    National Center of Neurology and Psychiatry, Japan
  • Shimizu Kimiko
    Food Science Institute, Division of Research and Development, Meiji Co., Ltd., Japan
  • Amano Tomofumi
    National Center of Neurology and Psychiatry, Japan
  • Ariga Hajime
    National Center of Neurology and Psychiatry, Japan

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Mosapride citrate hydrate (mosapride) has been known to act as a 5-HT4 agonist and to enhance gastric emptying. However, its mode of action, such as time course and dosage effect, on gastric emptying has not been clarified. This study aimed to clarify these points by the breath test using [1-13C]acetic acid in conscious rats. Mosapride significantly and dose-dependently enhanced the gastric emptying increased Cmax and AUC120 min at doses between 0.1 and 3 mg/kg. Pre-treatment with GR113808 (5-HT4 antagonist) significantly attenuated the enhancement of gastric emptying by mosapride. On the contrary, at a dose of 30 mg/kg, mosapride significantly inhibited the gastric emptying. The major metabolite (M1: 5-HT3 receptor antagonist) significantly inhibited gastric emptying at doses of 19.2 and 64.1 mg/kg (equimolar to 30 and 100 mg/kg of mosapride, respectively), suggesting that the inhibitory effect by mosapride may be caused at least in part by the 5-HT3 receptor antagonistic effect of M1. These findings show that mosapride has dual role on the gastric emptying and may support the usefulness of mosapride for the therapy of postprandial distress syndrome such as early satiation and postprandial fullness.

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