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Effects of mosapride citrate, a 5-HT4 receptor agonist, on colonic motility in conscious guinea pigs.

AbstractIt is known that 5-HT(4) 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-HT(4)-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-HT(4)-receptor antagonist, but not by methysergide, a 5-HT(1)- and 5-HT(2)-receptor antagonist; ondansetron, a 5-HT(3)-receptor antagonist; or CP-99994, a tachykinin NK(1)-receptor antagonist. In vitro receptor autoradiography showed that mosapride and cisapride inhibit the specific binding of [(125)I]-SB207710, a selective radioligand of 5-HT(4) receptors, in the colon of guinea pigs. These results suggest that mosapride enhances colonic motility through the 5-HT(4)-receptor activation in guinea pigs and may be useful for treating constipation in patients with colonic motility dysfunction.
AuthorsAtsuko Inui, Takashi Yoshikawa, Ryuji Nagai, Naoyuki Yoshida, Tsugutaka Ito (Affiliation: Department of Safety Pharmacology, Developmental Research Laboratories, Dainippon Pharmaceutical Co., Ltd., Suita, Osaka, Japan.)
JournalJapanese journal of pharmacology (Jpn J Pharmacol) Vol. 90 Issue 4 Pg. 313-20 (Dec 2002) ISSN: 0021-5198 [Print] Japan
PMID12501007 (Publication Type: Comparative Study, Journal Article)
Chemical References
  • Benzamides
  • Dioxanes
  • Morpholines
  • Piperidines
  • Receptors, Serotonin
  • SB 207710
  • Serotonin Agonists
  • Serotonin Antagonists
  • mosapride
Topics
  • Animals
  • Autoradiography
  • Benzamides (pharmacology)
  • Colon (drug effects, metabolism, physiology)
  • Dioxanes (metabolism)
  • Dose-Response Relationship, Drug
  • Gastrointestinal Motility (drug effects)
  • Guinea Pigs
  • Male
  • Morpholines (pharmacology)
  • Piperidines (metabolism)
  • Radioligand Assay
  • Receptors, Serotonin (drug effects, metabolism)
  • Serotonin Agonists (pharmacology)
  • Serotonin Antagonists (pharmacology)
  • Time Factors

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