Effects of Mosapride Citrate, a 5-HT4 Receptor Agonist, on Colonic Motility in Conscious Guinea Pigs.

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  • Inui Atsuko
    Department of Safety Pharmacology, Developmental Research Laboratories, Dainippon Pharmaceutical Co., Ltd.
  • Yoshikawa Takashi
    Department of Pharmacology I, Discovery Research Laboratories, Dainippon Pharmaceutical Co., Ltd.
  • Nagai Ryuji
    Department of R&D Group of Biocybernetics, Dainippon Pharmaceutical Co., Ltd.
  • Yoshida Naoyuki
    Department of Pharmacology I, Discovery Research Laboratories, Dainippon Pharmaceutical Co., Ltd.
  • Ito Tsugutaka
    Department of Safety Pharmacology, Developmental Research Laboratories, Dainippon Pharmaceutical Co., Ltd.

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説明

It is known that 5-HT4 receptors in the colon of guinea pigs show a distribution similar to that in humans. Thus, we examined the effects of mosapride citrate (mosapride) and cisapride, two 5-HT4-receptor agonists, on colonic motility in conscious guinea pigs implanted with force transducers. Mosapride and cisapride administered intragastrically at doses of 3 – 30 mg/kg significantly enhanced the colonic motility. The enhancing effect of mosapride was antagonized by atropine or GR113808, a 5-HT4-receptor antagonist, but not by methysergide, a 5-HT1- and 5-HT2-receptor antagonist; ondansetron, a 5-HT3-receptor antagonist; or CP-99994, a tachykinin NK1-receptor antagonist. In vitro receptor autoradiography showed that mosapride and cisapride inhibit the specific binding of [125I]-SB207710, a selective radioligand of 5-HT4 receptors, in the colon of guinea pigs. These results suggest that mosapride enhances colonic motility through the 5-HT4-receptor activation in guinea pigs and may be useful for treating constipation in patients with colonic motility dysfunction.<br>

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  • Jpn.J.Pharmacol.

    Jpn.J.Pharmacol. 90 (4), 313-320, 2002

    公益社団法人 日本薬理学会

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