Mosapride

Mosapride
Systematic (IUPAC) name
(RS)-4-amino-5-chloro-2-ethoxy-N-{[4-(4-fluorobenzyl)morpholin-2-yl]methyl}benzamide
Clinical data
AHFS/Drugs.com International Drug Names
Identifiers
112885-41-3 
None
PubChem CID 119584
IUPHAR ligand 242
ChemSpider 106780 Yes
UNII I8MFJ1C0BY Yes
KEGG D08236 Yes
ChEMBL CHEMBL60889 Yes
Chemical data
Formula C21H25ClFN3O3
421.893 g/mol
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Mosapride is a gastroprokinetic agent that acts as a selective 5HT4 agonist. The major active metabolite of mosapride, known as M1, additionally acts as a 5HT3 antagonist.[1] which accelerates gastric emptying throughout the whole of the gastrointestinal tract in humans,[2] and is used for the treatment of gastritis, gastro-oesophageal reflux disease, functional dyspepsia[3] and irritable bowel syndrome.[4] It is recommended to be taken on an empty stomach (i.e. at least one hour before food or two hours after food).[5]

In addition to its prokinetic properties, mosapride also exerts anti-inflammatory effects on the gastrointestinal tract which may contribute to some of its therapeutic effects.[6] Mosapride also promotes neurogenesis in the gastrointestinal tract which may prove useful in certain bowel disorders.[7][8] The neurogenesis is due to mosapride's effect on the 5-HT4 receptor where it acts as an agonist.[9]

Its common side effects include dry mouth, abdominal pain, dizziness, headache, insomnia, malaise, nausea, diarrhoea and sometimes constipation.[3][10] Unlike some other prokinetic agents, mosapride has little effect on potassium channels, no effect on hERG transfected cells, and no effect on cardiovascular function that could be detected in tests on humans.[1][11] Due to the pharmacokinetics of mosapride, it would take 1,000 - 3,000 times the therapeutic dose to elicit cardiovascular effects.[12]

References

  1. ↑ 1.0 1.1 Tack, J.; Camilleri, M.; Chang, L.; Chey, WD.; Galligan, JJ.; Lacy, BE.; Müller-Lissner, S.; Quigley, EM.; Schuurkes, J. (Apr 2012). "Systematic review: cardiovascular safety profile of 5-HT(4) agonists developed for gastrointestinal disorders.". Aliment Pharmacol Ther 35 (7): 745–67. doi:10.1111/j.1365-2036.2012.05011.x. PMID 22356640.
  2. ↑ Odaka T, Suzuki T, Seza A, Yamaguchi T, Saisho H (August 2006). "[Serotonin 5- HT4 receptor agonist (mosapride citrate)]". Nippon Rinsho (in Japanese) 64 (8): 1491–4. PMID 16898619.
  3. ↑ 3.0 3.1 Curran MP, Robinson DM (2008). "Mosapride in gastrointestinal disorders". Drugs 68 (7): 981–91. doi:10.2165/00003495-200868070-00007. PMID 18457463.
  4. ↑ Mizuta Y, Shikuwa S, Isomoto H, Mishima R, Akazawa Y, Masuda J, Omagari K, Takeshima F, Kohno S. Recent insights into digestive motility in functional dyspepsia. Journal of Gastroenterology. 2006 Nov;41(11):1025-40.
  5. ↑ Kato S, Morie T, Yoshida N. Synthesis and biological activities of metabolites of mosapride, a new gastroprokinetic agent.Chemical and Pharmaceutical Bulletin (Tokyo). 1995 Apr;43(4):699-702.
  6. ↑ Tsuchida Y, Hatao F, Fujisawa M et al. (May 2011). "Neuronal stimulation with 5-hydroxytryptamine 4 receptor induces anti-inflammatory actions via α7nACh receptors on muscularis macrophages associated with postoperative ileus". Gut 60 (5): 638–47. doi:10.1136/gut.2010.227546. PMC 3071096. PMID 21115544.
  7. ↑ Kawahara I, Kuniyasu H, Matsuyoshi H et al. (March 2012). "Comparison of effects of a selective 5-HT reuptake inhibitor versus a 5-HT4 receptor agonist on in vivo neurogenesis at the rectal anastomosis in rats". Am. J. Physiol. Gastrointest. Liver Physiol. 302 (6): G588–97. doi:10.1152/ajpgi.00284.2011. PMID 22194416.
  8. ↑ Matsuyoshi H, Kuniyasu H, Okumura M et al. (July 2010). "A 5-HT(4)-receptor activation-induced neural plasticity enhances in vivo reconstructs of enteric nerve circuit insult". Neurogastroenterol. Motil. 22 (7): 806–13, e226. doi:10.1111/j.1365-2982.2010.01474.x. PMID 20146727.
  9. ↑ Goto, K.; Kato, G.; Kawahara, I.; Luo, Y.; Obata, K.; Misawa, H.; Ishikawa, T.; Kuniyasu, H.; Nabekura, J.; Takaki, M (2013). "In vivo imaging of enteric neurogenesis in the deep tissue of mouse small intestine.". PLoS One 8 (1): e54814. doi:10.1371/journal.pone.0054814. PMID 23382976.
  10. ↑ Mosapride drug information - Drugs Update India
  11. ↑ Kii, Y.; Ito, T. (May 1997). "Effects of 5-HT4-receptor agonists, cisapride, mosapride citrate, and zacopride, on cardiac action potentials in guinea pig isolated papillary muscles". J Cardiovasc Pharmacol 29 (5): 670–5. doi:10.1097/00005344-199705000-00016. PMID 9213211.
  12. ↑ Kii, Y.; Ito, T. (May 2002). "Drug-induced ventricular tachyarrhythmia in isolated rabbit hearts with atrioventricular block". Pharmacol Toxicol 90 (5): 246–53. doi:10.1034/j.1600-0773.2002.900504.x. PMID 12076305.