Mosapride Citrate

5-HT₄ receptor agonist and 5-HT₃ receptor antagonist. Displays no activity at D₂, α₁, α₂, 5-HT₁ and 5-HT₂ receptors. Gastroprokinetic agent; increases gastric emptyin

Measurement of Human Cytochrome P450 Enzyme Induction Based on Mesalazine and Mosapride Citrate Treatments Using a Luminescent Assay.[Pubmed:26336590]

Biomol Ther (Seoul). 2015 Sep;23(5):486-92.

Drug metabolism mostly occurs in the liver. Cytochrome P450 (CYP) is a drug-metabolizing enzyme that is responsible for many important drug metabolism reactions. Recently, the US FDA and EU EMA have suggested that CYP enzyme induction can be measured by both enzymatic activity and mRNA expression. However, these experiments are time-consuming and their inter-assay variability can lead to misinterpretations of the results. To resolve these problems and establish a more powerful method to measure CYP induction, we determined CYP induction by using luminescent assay. Luminescent CYP assays link CYP enzyme activity to firefly luciferase luminescence technology. In this study, we measured the induction of CYP isozymes (1A2, 2B6, 2C9, and 3A4) in cryopreserved human hepatocytes (HMC424, 478, and 493) using a luminometer. We then examined the potential induction abilities (unknown so far) of mesalazine, a drug for colitis, and Mosapride Citrate, which is used as an antispasmodic drug. The results showed that mesalazine promotes CYP2B6 and 3A4 activities, while Mosapride Citrate promotes CYP1A2, 2B6, and 3A4 activities. Luminescent CYP assays offer rapid and safe advantages over LC-MS/MS and qRT-PCR methods. Furthermore, luminescent CYP assays decrease the interference between the optical properties of the test compound and the CYP substrates. Therefore, luminescent CYP assays are less labor intensive, rapid, and can be used as robust tools for high-throughput CYP screening during early drug discovery.

Mosapride citrate increases postprandial glucagon-like peptide-1, insulin, and gene expression of sweet taste receptors.[Pubmed:25008428]

Dig Dis Sci. 2015 Feb;60(2):345-53.

BACKGROUND AND AIM: Mosapride Citrate-a prokinetic agent-improves hemoglobin A1c levels in diabetic patients; however, the underlying mechanism is unclear. We aimed to clarify this mechanism. METHODS: Preprandial and postprandial (90 min after a meal) blood was obtained from 12 healthy men, and serum insulin and plasma active glucagon-like peptide-1 concentrations were measured. Measurements were also taken after the administration of 5 mg of Mosapride Citrate three times per day after every meal for 14 days. In addition, C57BL/6 mice were permitted free access to water containing 0.04 % domperidone (D group) or 0.02 % Mosapride Citrate (M group) for 2 weeks (four mice per group). T1r2 (taste receptor, type 1, member 2), T1r3, and Gnat3 (guanine nucleotide-binding protein, alpha transducing 3) mRNA expression levels of the stomach, duodenum, and proximal and mid-jejunum were evaluated. RESULTS: In human subjects, postprandial plasma active glucagon-like peptide-1 and serum insulin concentrations after administration of Mosapride Citrate were significantly higher than those pre-administration (4.8 +/- 2.2 pmol/L, 45.6 +/- 41.6 muIU/mL, and 3.7 +/- 1.2 pmol/L, 34.1 +/- 28.4 muIU/mL, respectively). The mouse expression levels of T1r2 and Gnat3 in the proximal jejunum and mid-jejunum in the M group (4.1 +/- 1.8-fold, 3.1 +/- 1.6-fold, and 4.6 +/- 0.8-fold, 3.1 +/- 0.9-fold increases, respectively), were significantly higher than those of the control group. CONCLUSIONS: The administration of Mosapride Citrate for 2 weeks enhanced postprandial plasma active glucagon-like peptide-1 and serum insulin concentration and increased the expression of sweet taste receptors in the upper intestine.

Mosapride citrate improves nonalcoholic steatohepatitis with increased fecal lactic acid bacteria and plasma glucagon-like peptide-1 level in a rodent model.[Pubmed:25428903]

Am J Physiol Gastrointest Liver Physiol. 2015 Jan 15;308(2):G151-8.

Several lines of evidence have suggested a role of gut microbiota in the etiology of nonalcoholic steatohepatitis (NASH). NASH subjects reportedly showed a prolonged orocecal transit time coexistent with small intestinal bacterial overgrowth. We considered the possibility that enhanced gastrointestinal motility would influence gut microbiota and thus investigated the effects of the gastroprokinetic agent Mosapride Citrate (MC) on gut microbiota and the development of NASH using a methionine-choline deficient (MCD) diet-fed rodent model. Mice were divided into three groups, given the normal chow diet (NCD), the MCD diet, or the MCD diet containing 10 mg.kg(-1).day(-1) of MC (MCD plus MC) for 6 wk. NASH development was evaluated based on hepatic histochemical findings, serum parameters and various mRNA and/or protein expression levels. MC treatment suppressed MCD diet-induced NASH development, with reduced serum lipopolysaccharide and increased plasma glucagon-like peptide-1 (GLP-1) concentrations. Calculation of the relative abundance of each strain based on gut microbiota analyses indicated lactic acid bacteria specifically, such as Bifidobacterium and Lactobacillus, in feces to be decreased in the MCD, compared with the NCD group. Interestingly, the reduction in lactic acid bacteria in the MCD diet group was reversed in the MCD plus MC group. In addition, colon inflammation observed in the MCD diet group was reduced in the MCD plus MC group. Therefore, MC showed a protective effect against MCD diet-induced NASH development in our rodent model, with possible involvements of increased fecal lactic acid bacteria, protection against colon inflammation and elevated plasma GLP-1.

Drug-induced Liver Injury Associated with Mosapride Citrate: A Report of Two Cases.[Pubmed:28049998]

Intern Med. 2017;56(1):41-45.

We herein report two cases of drug-induced liver injury (DILI) due to mosapride. Case 1: A 78-year-old man was admitted with elevated transaminase levels. The cessation of mosapride led to the improvement of elevated liver enzyme levels. Case 2: A 54-year-old man was admitted with jaundice. Mosapride was discontinued immediately, and methylprednisolone was administered for acute liver failure. The patient's data showed improvement, and he was discharged on Day 32. In both cases, mosapride gave a positive response to a drug-induced lymphocyte stimulation test (DLST), and the patient's score based on the criteria for DILI was "highly probable".

Comparison of effect of mosapride citrate and existing 5-HT4 receptor agonists on gastrointestinal motility in vivo and in vitro.[Pubmed:9399969]

J Pharmacol Exp Ther. 1997 Dec;283(3):1000-8.

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.

AS-4370, a novel gastrokinetic agent free of dopamine D2 receptor antagonist properties.[Pubmed:2533479]

Arch Int Pharmacodyn Ther. 1989 Jul-Aug;300:51-67.

The gastrokinetic effects of AS-4370, 4-amino-5-chloro-2-ethoxy-N-([4-(4-fluorobenzyl)-2-morpholinyl] methyl) benzamide citrate, were compared with those of metoclopramide in experimental animals. In rats, AS-4370 increased the gastric emptying of a semi-solid meal and of resin pellets at dose ranges of 0.03-30 mg/kg and 1-10 mg/kg p.o., respectively. The minimal effective doses were 3-10 times lower than those of metoclopramide. Gastric emptying, delayed by gastroduodenal surgical intervention, was improved with AS-4370 (0.3-3 mg/kg p.o.). In conscious dogs with strain gauges implanted, AS-4370 (0.5 and 1.0 mg/kg i.v.) enhanced antral and duodenal motility without affecting ileal and colonic motility, indicating a selective enhancing effect on upper gastrointestinal motility. AS-4370 (10(-7) - 3 x 10(-5) M) increased electrically evoked, cholinergically mediated contractions in isolated guinea-pig ileum. AS-4370 (3 mg/kg i.v.) was without effect on gastric acid secretion in anesthetized rats. Unlike metoclopramide, AS-4370 neither depressed the active avoidance response in mice nor the food-reinforced lever pressing response in rats, even at 100 mg/kg p.o. Moreover, AS-4370 (10(-4) M) showed no affinity for D2, alpha 1, alpha 2, 5-HT1 and 5-HT2 binding sites in rat brain synaptic membranes. These results suggest that AS-4370 is a new and potent gastrokinetic agent that lacks dopamine D2 receptor antagonist properties.