title: Effects of mosapride citrate, a 5-HT4-receptor agonist, on gastric distension-induced visceromotor response in conscious rats.
abstract: Mosapride citrate (mosapride), a prokinetic agent with 5-HT(4)-receptor agonistic activity, is known to enhance gastric emptying and alleviate symptoms in patients with functional dyspepsia (FD). As hyperalgesia and delayed gastric emptying play an important role in the pathogenesis of FD, we used in this study balloon gastric distension to enable abdominal muscle contractions and characterized the visceromotor response (VMR) to such distension in conscious rats. We also investigated the effects of mosapride on gastric distension-induced VMR in the same model. Mosapride (3-10 mg/kg, p.o.) dose-dependently inhibited gastric distension-induced VMR in rats. However, itopride even at 100 mg/kg failed to inhibit gastric distension-induced VMR in rats. Additionally, a major metabolite M1 of mosapride, which possesses 5-HT(3)-receptor antagonistic activity, inhibited gastric distension-induced VMR. The inhibitory effect of mosapride on gastric distension-induced visceral pain was partially, but significantly inhibited by SB-207266, a selective 5-HT(4)-receptor antagonist. This study shows that mosapride inhibits gastric distension-induced VMR in conscious rats. The inhibitory effect of mosapride is mediated via activation of 5-HT(4) receptors and blockage of 5-HT(3) receptors by a mosapride metabolite. This finding indicates that mosapride may be useful in alleviating FD-associated gastrointestinal symptoms via increase in pain threshold.
authors.affiliation: Genomic Research Laboratories, Dainippon Sumitomo Pharma. Co., Ltd., Suita, Osaka 564-0053, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Seto
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Yoshida
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kaneko
mesh_terms: D015746:Abdominal Pain / Q000188:drug therapy; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000627:therapeutic use; D000818:Animals; D001549:Benzamides / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D001593:Benzyl Compounds / Q000008:administration & dosage / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004415:Dyspepsia / Q000188:drug therapy; D013271:Gastric Dilatation / Q000503:physiopathology*; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000627:therapeutic use*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D017829:Granisetron / Q000627:therapeutic use; D008297:Male; D009025:Morpholines / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012020:Reflex, Abdominal / Q000187:drug effects*; D058827:Serotonin 5-HT3 Receptor Agonists / Q000627:therapeutic use; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000494:pharmacology; D058828:Serotonin 5-HT4 Receptor Agonists / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D058832:Serotonin 5-HT4 Receptor Antagonists / Q000494:pharmacology; D013270:Stomach / Q000187:drug effects / Q000294:innervation*
chemical_list: D018712:Analgesics, Non-Narcotic; D001549:Benzamides; D001593:Benzyl Compounds; D005765:Gastrointestinal Agents; D017829:Granisetron; D009025:Morpholines; D058827:Serotonin 5-HT3 Receptor Agonists; D058831:Serotonin 5-HT3 Receptor Antagonists; D058828:Serotonin 5-HT4 Receptor Agonists; D058832:Serotonin 5-HT4 Receptor Antagonists; C467826:des-4-fluorobenzyl-mosapride; C102254:itopride; C062720:mosapride