Effects of mosapride citrate, a 5-HT4 receptor agonist, on colonic motility in conscious guinea pigs.
It 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.
Inui
Atsuko
A
Department of Safety Pharmacology, Developmental Research Laboratories, Dainippon Pharmaceutical Co., Ltd., Suita, Osaka, Japan.
Yoshikawa
Takashi
T
Nagai
Ryuji
R
Yoshida
Naoyuki
N
Ito
Tsugutaka
T
D000818:Animals; D001345:Autoradiography; D001549:Benzamides / Q000494:pharmacology*; D003106:Colon / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D004146:Dioxanes / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006168:Guinea Pigs; D008297:Male; D009025:Morpholines / Q000494:pharmacology*; D010880:Piperidines / Q000378:metabolism; D011869:Radioligand Assay; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013997:Time Factors
D001549:Benzamides; D004146:Dioxanes; D009025:Morpholines; D010880:Piperidines; D011985:Receptors, Serotonin; C088873:SB 207710; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C062720:mosapride