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OtherGASTROINTESTINAL PHARMACOLOGY

Comparison of Effect of Mosapride Citrate and Existing 5-HT4 Receptor Agonists on Gastrointestinal MotilityIn Vivo and In Vitro

Yukiko Mine, Takashi Yoshikawa, Seiko Oku, Ryuji Nagai, Naoyuki Yoshida and Kanoo Hosoki
Journal of Pharmacology and Experimental Therapeutics December 1997, 283 (3) 1000-1008;
Yukiko Mine
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Takashi Yoshikawa
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Seiko Oku
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Ryuji Nagai
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Naoyuki Yoshida
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Kanoo Hosoki
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Abstract

Mosapride citrate is a new gastroprokinetic agent that enhances the upper GI motility by stimulating 5-hydroxytryptamine4(5-HT4) receptors. The purpose of this study was to compare the effects of mosapride and the existing 5-HT4 receptor agonists on GI motility in conscious dogs and on various 5-HT4 receptor-mediated responses in vitro. In conscious dogs with force transducers implanted, mosapride (0.3–3 mg/kg i.v.) stimulated the antral motility without affecting the colonic motility. However, cisapride, zacopride and BIMU 8 (0.1–1 mg/kg i.v.) stimulated both antral and colonic motility. The enhanced GI motility induced by mosapride or cisapride was antagonized by pretreatment with GR113808 (1 mg/kg bolus i.v., thereafter 1 mg/kg/hr infusion), a selective 5-HT4 receptor antagonist. In the receptor binding studies, mosapride inhibited [3H]-GR113808 binding to 5-HT4 receptor sites of guinea pig striatum with an IC50 value of 113 nM. In addition, mosapride caused relaxation of the carbachol-precontracted rat esophagus, enhanced the electrically evoked contractions of guinea pig ileum and evoked the contractions of guinea pig distal colon with EC50 values of 208, 73, and 3029 nM, respectively; this indicates that mosapride has a low affinity for colon than for the rest of the GI tract. In contrast, cisapride, zacopride or BIMU 8 had similar potencies in all preparations examined. In conclusion, these studies indicate that mosapride selectively stimulates upper GI motility in vivo and in vitro. These results also suggest heterogeneity of 5-HT4 receptors in the GI tract.

Footnotes

  • Send reprint requests to: Yukiko Mine, Department of Pharmacology I, Discovery Research Laboratories I, Dainippon Pharmaceutical Co., Ltd., Enoki 33-94, Suita, Osaka, Japan. Post Code 564.

  • Abbreviations:
    5-HT
    5-hydroxytryptamine
    GMC
    giant migrating contractions
    LMMP
    longitudinal muscle myenteric plexus
    • Received June 25, 1996.
    • Accepted July 2, 1997.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics
Vol. 283, Issue 3
1 Dec 1997
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OtherGASTROINTESTINAL PHARMACOLOGY

Comparison of Effect of Mosapride Citrate and Existing 5-HT4 Receptor Agonists on Gastrointestinal MotilityIn Vivo and In Vitro

Yukiko Mine, Takashi Yoshikawa, Seiko Oku, Ryuji Nagai, Naoyuki Yoshida and Kanoo Hosoki
Journal of Pharmacology and Experimental Therapeutics December 1, 1997, 283 (3) 1000-1008;

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OtherGASTROINTESTINAL PHARMACOLOGY

Comparison of Effect of Mosapride Citrate and Existing 5-HT4 Receptor Agonists on Gastrointestinal MotilityIn Vivo and In Vitro

Yukiko Mine, Takashi Yoshikawa, Seiko Oku, Ryuji Nagai, Naoyuki Yoshida and Kanoo Hosoki
Journal of Pharmacology and Experimental Therapeutics December 1, 1997, 283 (3) 1000-1008;
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