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Naoyuki Yoshida - One of the best experts on this subject based on the ideXlab platform.
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anti emetic effect of Mosapride citrate hydrate a 5 ht4 receptor agonist on selective serotonin reuptake inhibitors ssris induced emesis in experimental animals
Journal of Pharmacological Sciences, 2013Co-Authors: Yukiko Mine, Seiko Oku, Naoyuki YoshidaAbstract:Although selective serotonin reuptake inhibitors (SSRIs) are widely used to treat depression, they frequently cause gastrointestinal adverse effects, such as nausea and emesis. In the present study, we investigated the anti-emetic effect of Mosapride, a 5-HT(4) receptor agonist, on SSRIs-induced emesis in Suncus murinus and dogs. We also examined the effect of Mosapride on SSRIs-induced delay in gastric emptying and increase in gastric vagal afferent activity in rats. Oral administration of paroxetine, but not its subcutaneous administration, dose-dependently caused emesis in both animals. Mosapride inhibited paroxetine-induced emesis in Suncus murinus and dogs with ID(50) values of 7.9 and 1.1 mg/kg, respectively. The anti-emetic effect of Mosapride was partially inhibited by SB207266, a selective 5-HT(4) antagonist. Intragastric administration of paroxetine increased gastric vagal afferent discharge in anesthetized rats. Mosapride failed to suppress this increase. On the other hands, Mosapride improved the delay in gastric emptying caused by paroxetine in rats. We have shown in this study that oral administration of SSRIs causes emesis and activates gastric vagal afferent activity in experimental animals and that Mosapride inhibits SSRIs-induced emesis, probably via improvement of SSRIs-induced delay in gastric emptying. These findings highlight the promising potential of Mosapride as an anti-emetic agent.
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Effects of Mosapride citrate, a 5-HT4-receptor agonist, on gastric distension-induced visceromotor response in conscious rats.
Journal of pharmacological sciences, 2011Co-Authors: Yasuhiro Seto, Naoyuki Yoshida, Hiroshi KanekoAbstract: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.
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synthesis and biological activities of metabolites of Mosapride a new gastroprokinetic agent
ChemInform, 2010Co-Authors: Shiro Kato, Toshiya Morie, Naoyuki YoshidaAbstract:In order to confirm the proposed structures of two metabolites 3 and 4 of the gastroprokinetic agent Mosapride [4-amino-5-chloro-2-ethoxy-N-{[4-(4-fluorobenzyl)-2-morpholinyl]methyl}benzamide, 2], the compounds were synthesized and their biological activity was examined. The structures of the metabolites were confirmed by means of comparison with the synthetic compounds. The serotonin 5-HT4 receptor agonistic activities of the metabolites were found to be less than that of Mosapride.
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Effects of Mosapride Citrate, a 5-HT4 Receptor Agonist, on Colonic Motility in Conscious Guinea Pigs
Japanese Journal of Pharmacology, 2002Co-Authors: Atsuko Inui, Ryuji Nagai, Takashi Yoshikawa, Naoyuki YoshidaAbstract:It is known that 5-HT4 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-HT4-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-HT4-receptor antagonist, but not by methysergide, a 5-HT1- and 5-HT2-receptor antagonist; ondansetron, a 5-HT3-receptor antagonist; or CP-99994, a tachykinin NK1-receptor antagonist. In vitro receptor autoradiography showed that Mosapride and cisapride inhibit the specific binding of [125I]-SB207710, a selective radioligand of 5-HT4 receptors, in the colon of guinea pigs. These results suggest that Mosapride enhances colonic motility through the 5-HT4-receptor activation in guinea pigs and may be useful for treating constipation in patients with colonic motility dysfunction.
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Affinity of Mosapride citrate, a new gastroprokinetic agent, for 5-HT4 receptors in guinea pig ileum
Japanese journal of pharmacology, 1998Co-Authors: Takashi Yoshikawa, Naoyuki Yoshida, Yukiko Mine, Kanoo HosokiAbstract:We examined the binding affinity of Mosapride citrate (Mosapride) (4-amino-5-chloro-2-ethoxy-N-[[4-(4-fluorobenzyl)-2-morpholinyl]me thyl] benzamide citrate), a novel gastroprokinetic agent, for the 5-hydroxytryptamine (5-HT) 4 receptors in guinea pig ileum using a selective 5-HT4-receptor radioligand, [3H]GR113808. In membrane preparations from longitudinal muscle with myenteric plexus in guinea pig ileum, specific [3H]GR113808 binding revealed a single saturable site of high affinity (Kd=0.28 +/-0.02 nM, Bmax = 45+/- 3 fmol/mg protein). Mosapride and other 5-HT4-receptor agonists inhibited the specific binding of [3H]GR113808 in guinea pig ileum. The 5-HT4 agonists examined displayed the following inhibition potency order: BIMU-8 > cisapride > Mosapride > renzapride > 5-HT > zacopride > metoclopramide. Mosapride exhibited monophasic inhibition of the specific [3H]GR113808 binding in the ileum (Ki value: 84.2 nM). The presence of Mosapride (30 nM) significantly increased the Kd value to 0.44+/-0.05 nM in the Scatchard analysis of [3H]GR113808 binding. Bmax of [3H]GR113808, however, was not affected (48 +/-4 fmol/mg protein) by Mosapride. As for the affinity of Mosapride, the addition of GppNHp (100microM) slightly increased the Ki value to 104 nM. These results indicate that Mosapride has an affinity for 5-HT4 receptors in guinea pig ileum in the radioligand binding study.
Shin Fukudo - One of the best experts on this subject based on the ideXlab platform.
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Effect of 5‐hydroxytryptamine receptor 4 agonist Mosapride on human gastric accommodation
Neurogastroenterology and Motility, 2015Co-Authors: Tomofumi Amano, Ayako Kurematsu, Shigeru Yamato, A. Masaka, Motoyori Kanazawa, Hajime Ariga, S Morioka, Shin FukudoAbstract:Background Impaired gastric accommodation is one of the major features of functional dyspepsia. Mosapride citrate is a 5-hydroxytryptamine receptor 4 (5-HT4) agonist, which is shown to improve upper abdominal symptoms. However, effect of Mosapride on gastric accommodation was not clear. We tested the hypothesis that Mosapride enhances the gastric accommodation in normal individuals. Methods Fourteen male healthy volunteers completed this study. Single administration of Mosapride or placebo was performed randomly with more than 1-week interval. Subjects swallowed a triple-lumen polyvinyl tube with a polyethylene bag. The bag was positioned in the proximal stomach and the minimal distending pressure (MDP) was determined. The ramp distension starting from the MDP was then performed and subjects were instructed to score their perception using ordinate scales. Next the intra-bag pressure was set at MDP + 2 mmHg and a liquid meal was administered 30 min later, and the intra-bag volume was recorded for 60 min. We compared the MDP, perception scores, and the intra-bag volume changes by administering placebo and Mosapride. Key Results Minimal distending pressure was not significantly different in subjects receiving Mosapride or placebo. Treatment with Mosapride had no effect on intra-bag pressures or volumes inducing first sensation or discomfort. Gastric accommodation, expressed as the difference between pre- and postmeal intra-bag volumes, and the percent change of the intra-bag volumes by the meal was significantly enhanced by Mosapride compared with placebo. Conclusions & Inferences This is the first study clearly demonstrating that single administration of 5-HT4 agonist can enhance gastric accommodation in humans. (Umin.ac.jp, number UMIN000014063)
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effect of 5 ht4 receptor agonist Mosapride citrate on rectosigmoid sensorimotor function in patients with irritable bowel syndrome
Neurogastroenterology and Motility, 2011Co-Authors: Motoyori Kanazawa, Satoshi Watanabe, C Tana, Hazuki Komuro, Masashi Aoki, Shin FukudoAbstract:Background The 5-HT4 receptor agonist, Mosapride citrate, accelerates gastric emptying. However, the effect of Mosapride on colonic function has not been well investigated. We examined whether Mosapride changes rectosigmoid motility and perception in patients with irritable bowel syndrome (IBS). Methods Thirty-seven patients with IBS and 18 healthy subjects were studied. All subjects underwent a rectosigmoid barostat test to measure pain perception to intraluminal distention and resting smooth muscle motility for 20 min in the fasting state. Irritable bowel syndrome patients were then randomly assigned to receive either Mosapride 15 mg (n = 19) or placebo (n = 18) orally with 200 mL water. Rectosigmoid motility and perception were measured again for 60 min following dosing. Rectosigmoid tone and contractility were evaluated in each 10-min period. Key Results The pain threshold in the patients was significantly lower than that in controls (P < 0.01). There were no differences between Mosapride and placebo groups in pain threshold, barostat bag volume, or number of contractions at baseline. Mosapride significantly decreased the mean bag volume (P < 0.01; group × period interaction by two-way anova) and increased the mean number of contractions (P < 0.05) compared with placebo, but did not affect the perception. In IBS patients with constipation (i.e., excluding diarrhea-predominant subjects), Mosapride (n = 13) increased rectosigmoid tone (P < 0.01) and contractions (P < 0.05) more than placebo (n = 14). Conclusions & Inferences Mosapride stimulates colonic motility without any adverse effect. These findings suggest that Mosapride may have the potential to treat IBS patients with constipation and/or functional constipation. Further clinical trials are warranted to confirm the efficacy of this agent.
Yukiko Mine - One of the best experts on this subject based on the ideXlab platform.
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anti emetic effect of Mosapride citrate hydrate a 5 ht4 receptor agonist on selective serotonin reuptake inhibitors ssris induced emesis in experimental animals
Journal of Pharmacological Sciences, 2013Co-Authors: Yukiko Mine, Seiko Oku, Naoyuki YoshidaAbstract:Although selective serotonin reuptake inhibitors (SSRIs) are widely used to treat depression, they frequently cause gastrointestinal adverse effects, such as nausea and emesis. In the present study, we investigated the anti-emetic effect of Mosapride, a 5-HT(4) receptor agonist, on SSRIs-induced emesis in Suncus murinus and dogs. We also examined the effect of Mosapride on SSRIs-induced delay in gastric emptying and increase in gastric vagal afferent activity in rats. Oral administration of paroxetine, but not its subcutaneous administration, dose-dependently caused emesis in both animals. Mosapride inhibited paroxetine-induced emesis in Suncus murinus and dogs with ID(50) values of 7.9 and 1.1 mg/kg, respectively. The anti-emetic effect of Mosapride was partially inhibited by SB207266, a selective 5-HT(4) antagonist. Intragastric administration of paroxetine increased gastric vagal afferent discharge in anesthetized rats. Mosapride failed to suppress this increase. On the other hands, Mosapride improved the delay in gastric emptying caused by paroxetine in rats. We have shown in this study that oral administration of SSRIs causes emesis and activates gastric vagal afferent activity in experimental animals and that Mosapride inhibits SSRIs-induced emesis, probably via improvement of SSRIs-induced delay in gastric emptying. These findings highlight the promising potential of Mosapride as an anti-emetic agent.
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Affinity of Mosapride citrate, a new gastroprokinetic agent, for 5-HT4 receptors in guinea pig ileum
Japanese journal of pharmacology, 1998Co-Authors: Takashi Yoshikawa, Naoyuki Yoshida, Yukiko Mine, Kanoo HosokiAbstract:We examined the binding affinity of Mosapride citrate (Mosapride) (4-amino-5-chloro-2-ethoxy-N-[[4-(4-fluorobenzyl)-2-morpholinyl]me thyl] benzamide citrate), a novel gastroprokinetic agent, for the 5-hydroxytryptamine (5-HT) 4 receptors in guinea pig ileum using a selective 5-HT4-receptor radioligand, [3H]GR113808. In membrane preparations from longitudinal muscle with myenteric plexus in guinea pig ileum, specific [3H]GR113808 binding revealed a single saturable site of high affinity (Kd=0.28 +/-0.02 nM, Bmax = 45+/- 3 fmol/mg protein). Mosapride and other 5-HT4-receptor agonists inhibited the specific binding of [3H]GR113808 in guinea pig ileum. The 5-HT4 agonists examined displayed the following inhibition potency order: BIMU-8 > cisapride > Mosapride > renzapride > 5-HT > zacopride > metoclopramide. Mosapride exhibited monophasic inhibition of the specific [3H]GR113808 binding in the ileum (Ki value: 84.2 nM). The presence of Mosapride (30 nM) significantly increased the Kd value to 0.44+/-0.05 nM in the Scatchard analysis of [3H]GR113808 binding. Bmax of [3H]GR113808, however, was not affected (48 +/-4 fmol/mg protein) by Mosapride. As for the affinity of Mosapride, the addition of GppNHp (100microM) slightly increased the Ki value to 104 nM. These results indicate that Mosapride has an affinity for 5-HT4 receptors in guinea pig ileum in the radioligand binding study.
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comparison of effect of Mosapride citrate and existing 5 ht4 receptor agonists on gastrointestinal motility in vivo and in vitro
Journal of Pharmacology and Experimental Therapeutics, 1997Co-Authors: Yukiko Mine, Ryuji Nagai, Naoyuki Yoshida, Takashi Yoshikawa, Seiko Oku, Kanoo HosokiAbstract: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.
Motoyori Kanazawa - One of the best experts on this subject based on the ideXlab platform.
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Effect of 5‐hydroxytryptamine receptor 4 agonist Mosapride on human gastric accommodation
Neurogastroenterology and Motility, 2015Co-Authors: Tomofumi Amano, Ayako Kurematsu, Shigeru Yamato, A. Masaka, Motoyori Kanazawa, Hajime Ariga, S Morioka, Shin FukudoAbstract:Background Impaired gastric accommodation is one of the major features of functional dyspepsia. Mosapride citrate is a 5-hydroxytryptamine receptor 4 (5-HT4) agonist, which is shown to improve upper abdominal symptoms. However, effect of Mosapride on gastric accommodation was not clear. We tested the hypothesis that Mosapride enhances the gastric accommodation in normal individuals. Methods Fourteen male healthy volunteers completed this study. Single administration of Mosapride or placebo was performed randomly with more than 1-week interval. Subjects swallowed a triple-lumen polyvinyl tube with a polyethylene bag. The bag was positioned in the proximal stomach and the minimal distending pressure (MDP) was determined. The ramp distension starting from the MDP was then performed and subjects were instructed to score their perception using ordinate scales. Next the intra-bag pressure was set at MDP + 2 mmHg and a liquid meal was administered 30 min later, and the intra-bag volume was recorded for 60 min. We compared the MDP, perception scores, and the intra-bag volume changes by administering placebo and Mosapride. Key Results Minimal distending pressure was not significantly different in subjects receiving Mosapride or placebo. Treatment with Mosapride had no effect on intra-bag pressures or volumes inducing first sensation or discomfort. Gastric accommodation, expressed as the difference between pre- and postmeal intra-bag volumes, and the percent change of the intra-bag volumes by the meal was significantly enhanced by Mosapride compared with placebo. Conclusions & Inferences This is the first study clearly demonstrating that single administration of 5-HT4 agonist can enhance gastric accommodation in humans. (Umin.ac.jp, number UMIN000014063)
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effect of 5 ht4 receptor agonist Mosapride citrate on rectosigmoid sensorimotor function in patients with irritable bowel syndrome
Neurogastroenterology and Motility, 2011Co-Authors: Motoyori Kanazawa, Satoshi Watanabe, C Tana, Hazuki Komuro, Masashi Aoki, Shin FukudoAbstract:Background The 5-HT4 receptor agonist, Mosapride citrate, accelerates gastric emptying. However, the effect of Mosapride on colonic function has not been well investigated. We examined whether Mosapride changes rectosigmoid motility and perception in patients with irritable bowel syndrome (IBS). Methods Thirty-seven patients with IBS and 18 healthy subjects were studied. All subjects underwent a rectosigmoid barostat test to measure pain perception to intraluminal distention and resting smooth muscle motility for 20 min in the fasting state. Irritable bowel syndrome patients were then randomly assigned to receive either Mosapride 15 mg (n = 19) or placebo (n = 18) orally with 200 mL water. Rectosigmoid motility and perception were measured again for 60 min following dosing. Rectosigmoid tone and contractility were evaluated in each 10-min period. Key Results The pain threshold in the patients was significantly lower than that in controls (P < 0.01). There were no differences between Mosapride and placebo groups in pain threshold, barostat bag volume, or number of contractions at baseline. Mosapride significantly decreased the mean bag volume (P < 0.01; group × period interaction by two-way anova) and increased the mean number of contractions (P < 0.05) compared with placebo, but did not affect the perception. In IBS patients with constipation (i.e., excluding diarrhea-predominant subjects), Mosapride (n = 13) increased rectosigmoid tone (P < 0.01) and contractions (P < 0.05) more than placebo (n = 14). Conclusions & Inferences Mosapride stimulates colonic motility without any adverse effect. These findings suggest that Mosapride may have the potential to treat IBS patients with constipation and/or functional constipation. Further clinical trials are warranted to confirm the efficacy of this agent.
Hyojin Park - One of the best experts on this subject based on the ideXlab platform.
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effects of the addition of Mosapride to gastroesophageal reflux disease patients on proton pump inhibitor a prospective randomized double blind study
Journal of Neurogastroenterology and Motility, 2013Co-Authors: Hyun Chul Lim, Jie-hyun Kim, Young Hoon Youn, Eun Hee Lee, Byung Keon Lee, Hyojin ParkAbstract:Background/Aims Proton pump inhibitors (PPIs) which are the most effective agents for the treatment of gastroesophageal reflux disease (GERD), have been known to delay gastric emptying. Mosapride has been used as prokinetics by accelerating gastric emptying. We evaluated the efficacy of Mosapride to prevent PPI-induced delayed gastric emptying in a prospective randomized, double-blind and placebo-controlled trial.
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Endoscopic evaluation of gastric emptying and effect of Mosapride citrate on gastric emptying.
Yonsei medical journal, 2009Co-Authors: In Su Jung, Jie-hyun Kim, Hwal Youn Lee, Hyojin Park, Sang In LeeAbstract:Purpose: Gastric emptying has been evaluated by scintigraphy in spite of its limitations of time consumption, cost, and danger of radioisotope. Endoscopy is a simple technique, however, its validation for gastric emptying and quantification of food has not yet been investigated. The aim of our study was to assess endoscopic gastric emptying compared with scintigraphy and radiopaque markers (ROMs) studies. We also investigated the effect of a single dose of Mosapride on gastric emptying. Materials and Methods: Fifteen healthy volunteers underwent scintigraphy. Next day, subjects received a standard solid meal with ROMs and underwent endoscopy and simple abdomen X-ray after 3 hrs. After one week, the same procedure was repeated after ingestion of Mosapride (5 mg for group 1, n = 8; 10 mg for group 2, n = 7) 15 min before the meal. Quantification of gastric residue by endoscopy was scored from 0 to 3, and the scores were added up. Results: All subjects completed the study without any complication. The gastric emptying rate [T1/2 (min)] was in normal range (65.6 ± 12.6 min). Endoscopic gastric emptying was correlated significantly with gastric clearance of ROMs (r = 0.627, p = 0.012). Endoscopic gastric emptying and gastric clearance of ROMs after administration of Mosapride showed significant differences in the 10 mg group (p < 0.05). Conclusion: Endoscopy can evaluate gastric emptying safely and simply on an outpatient basis. A 10 mg dose of Mosapride enhanced gastric emptying, assessed by both endoscopy and ROMs.
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the effect of Mosapride citrate on proximal and distal colonic motor function in the guinea pig in vitro
Neurogastroenterology and Motility, 2007Co-Authors: Hyeongsoo Kim, Eun Jin Choi, Hyojin ParkAbstract:Abstract Mosapride citrate (Mosapride), a substituted benzamide, is a selective 5-HT4 receptor agonist, and is known to have prokinetic properties on the stomach. However, it is unclear whether Mosapride also has a prokinetic effect on the colon. We previously found that Mosapride significantly shortened colonic transit time in the guinea-pig, an animal with a distribution of colonic 5-HT4 receptors similar to that of a human. So, we aimed to separately evaluate the effect of Mosapride on proximal and distal colonic motor function in the guinea-pig. Proximal (approximately 8 cm from the ileocolic junction) and distal colon (approximately 8 cm from the anus) were removed. Both ends of the colon were connected to a chamber containing a Krebs-Henseleit solution. To measure colonic transit time, artificial faeces were inserted into the oral side of the lumen and moved towards the anal side by intraluminal perfusion via a peristaltic pump. A total of 6 cm of transit was observed and time was measured in 2 cm increments. A tissue bath study, using electrical stimulation, was performed to estimate the contractile activity of the circular musculature of the colon. Immunohistochemical staining for 5-HT4 receptors was performed in the myenteric plexus and circular muscle in both proximal and distal colon, and the stained area was measured using a microscope and computer software. Mosapride enhanced contraction at 10−9 to 10−7 mol L−1, coinciding with rapid transit both in proximal and distal colon. This pattern was more prominent in proximal colon. At the high dose (10−6 mol L−1) Mosapride had little or no effect on colonic contraction. This stimulatory effect was attenuated by GR113808, atropine and tetrodotoxin. In the myenteric plexus, the density of 5-HT4 receptors was significantly greater in the proximal colon than in the distal colon, but in circular muscle the density was greater in the distal colon. Thus, Mosapride accelerates transit through increased contraction in the proximal colon more than distal colon. The different distribution of neuronal and muscular 5-HT4 receptors may support these findings. Therefore, Mosapride may be a useful alternative to tegaserod and cisapride for constipation.