Description
Mosapride is an agonist of the serotonin (5-HT) receptor subtype 5-HT
4 (K
i = 69.9 nM). It is selective for 5-HT
4 over 5-HT
1, 5-HT
2, dopamine D
2, and α
1- and α
2-adrenergic receptors but acts as a partial antagonist at 5-HT
3 (K
i = 1,189 nM). It induces relaxation of precontracted rat esophageal thoracic muscularis mucosa preparations and enhances electrically evoked contractions in isolated guinea pig ileum (EC
50s = 208.4 and 73.2 nM, respectively). Mosapride (0.5 and 1 mg/kg, i.v.) increases antral and duodenal, but not ileal or colonic, motility in conscious dogs. It also increases gastric emptying in rats when administered at doses ranging from 0.03 to 30 mg/kg.
Uses
As a selective SR-4 activator and a SR-3 inhibitor, Mosapride(Mosapride citrate) is a gastroprokinetic agent that acts as a selective 5HT4 agonist which accelerates gastric emptying and is used for the treatment of acid reflux, irritable bowel syndrome and functional dyspepsia.
Uses
Mosapride Citrate is a selective SR-4 activator and a SR-3 inhibitor.
Biological Activity
5-HT 4 receptor agonist and 5-HT 3 receptor antagonist. Displays no activity at D 2 , α 1 , α 2 , 5-HT 1 and 5-HT 2 receptors. Gastroprokinetic agent; increases gastric emptying in rats and stimulates gastric motor actvity in conscious dogs.
Synthesis
GENERAL STEPS: To a suspension of 1.3 g (2.5 mmol) of 4-amino-5-chloro-2-ethoxy-N-((4-(4-fluorobenzyl)morpholin-2-yl)methyl)benzamide (Compound VIII) and 3 mL of water was added 12 mL of 117% aqueous hydrochloric acid. The resulting solution was stirred at 40°C for 3 hours, cooled to 10°C and 38 mL of 4M aqueous sodium hydroxide solution was added dropwise. The precipitated mosapride base (Compound IX) was filtered and washed twice with water to give 1.05 g (100%) of Compound IX.1.01 g of the above obtained Compound IX was warmed to boiling with 25 mL of 10% aqueous citric acid solution with stirring, cooled to 0°C, the precipitated product was filtered, and washed twice with water to give 1.34 g (86%) of 4-amino-5-chloro-2-ethanol oxy-N-((4-(4-fluorobenzyl)morpholin-2-yl)methyl)benzamide 2-hydroxypropane-1,2,3-tricarboxylate. Melting point: 110-113°C.
storage
room temperature (desiccate)
References
[1] Patent: WO2003/106440, 2003, A2. Location in patent: Page 10
