Effects of Mosapride Citrate on Human Plasma Levels of Motilin, Gastrin, Somatostatin, and Secretin.

Abstract

Mosapride citrate (mosapride) (4-amino-5-chloro-2-ethoxy-N-{[4-(4-fluorobenzyl)-2-morpholinyl]methyl}benzamidecitrate) is a novel gastroprokinetic agent that enhances gastrointestinal motility by stimulating the serotonin (5-HT 4 ) receptor. 1) This agent stimulates acetylcholine release from cholinergic neurons in the gastrointestinal wall and may enhance upper gastrointestinal motor activity in the postprandial state in conscious dogs. 2) We previously confirmed that cisapride causes significant increases in the level of motilin, a powerful inducer of gastrointestinal motor activity, in human plasma. 3) This result indicates that the actions of cisapride are closely related to changes in motilin in human plasma. Cisapride is a nonselective 5-HT 4 receptor agonist 4) and mosapride is a selective 5-HT 4 receptor agonist. 2) Furthermore, both agents have been used to improve gastrointestinal motility functions. Their effects on gastrointestinal motility are mainly regulated by hormonal and neuronal mechanisms. Therefore we examined the plasma levels of brain-gut peptides, which regulate gastrointestinal motility.The gastrointestinal peptide motilin is found in specific endocrine cells of the upper small intestine of hogs. 5) This peptide strongly stimulates fundic pouch activity 6) and plays an important physiological role in intestinal contractility, particularly in the fundus and antral of pouch of the stomach. It is one of the most important factors controlling the regular occurrence of phase III interdigestive migrating contractions. 7,8) Gastrin was first detected in extracts of pyloric antral mucosa. 9) The most potent actions of gastrin are stimulation of both gastric acid secretion and antral motility. 10) Somatostatin is present in high amounts in the stomach. 11) This peptide inhibits the secretion of motilin, gastrin, and secretin, and it also inhibits gastric, duodenal, and biliary motility. 12) Secretin, first isolated from porcine small intestine, 13) inhibits gastric acid secretion, gastrin release, and gastrointestinal motility. 14)The purpose of this study was to determine the effects of mosapride on plasma levels of motilin-, gastrin-, somatostatin-and secretin-immunoreactive substances (IS) in healthy individuals. MATERIALS AND METHODS SubjectsFive healthy male volunteers, aged 25-31 (median 28) years, and weighing 54-70 (median 65.1) kg, participated in the study. Each subject received information about the study's scientific purpose, which was approved by the Ethics Committee of Oita Medical University, and gave informed consent. No subject received any medication for two weeks preceding the test and no stimulator of gastrointestinal motility, except for mosapride, was administered to any subject during the study.Study Schedules Mosapride (Gasmotin tablets, Dainippon Pharmaceutical Co., Ltd., Osaka, Japan) was given orally as a single dose of 15 mg with water to the 5 volunteers. Two weeks later, placebo (lactose tablets) was given orally to the volunteers. Venous blood samples (10 ml) were t...

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The Effect of Nichin-to on the Plasma Gut-Regulatory Peptide Level in Healthy Human Subjects

“…Itoh et al reported that cisapride, a dopamine D 2 receptor antagonist and nonselective serotonin 5-HT 1, 3, 4 receptor agonist, induced a rise in plasma levels of motilin, gastrin and somatostatin, 5) while mosapride, a selective serotonin 5-HT 4 agonist, raised motilin and gastrin 6) plasma levels. We have investigated the effects of Sho-hange-ka-bukuryo-to, which is a Kampo medicine closely related to Nichin-to, on plasma gut-regulatory peptide levels.…”