Advertisement

Archives of Pharmacal Research

, Volume 34, Issue 6, pp 861–864 | Cite as

Trimebutine as a modulator of gastrointestinal motility

  • Hyun-Tai Lee
  • Byung Joo Kim
This Month in Apr

Abstract

Trimebutine has been used for treatment of both hypermotility and hypomotility disorders of the gastrointestinal (GI) tract, such as irritable bowel syndrome. In this issue, Tan et al. (2011) examined the concentration-dependent dual effects of trimebutine on colonic motility in guinea pig. The authors suggested that trimebutine attenuated colonic motility mainly through the inhibition of L-type Ca2+ channels at higher concentrations, whereas, at lower concentrations, it depolarized membrane potentials by reducing BKca currents, resulting in the enhancement of the muscle contractions. Trimebutine might be a plausible modulator of GI motility, which gives an insight in developing new prokinetic agents. Further studies to elucidate the effects of trimebutine on the interstitial cells of Cajal, the pacemaker in GI muscles would promote the therapeutic benefits as a GI modulator.

Keywords

Irritable Bowel Syndrome Interstitial Cell Tegaserod Colonic Motility Trimebutine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Delvaux, M. and Wingate, D., Trimebutine: mechanism of action, effects on gastrointestinal function and clinical results. J. Int. Med. Res., 25, 225–246 (1997).PubMedGoogle Scholar
  2. Farrugia, G., Ca2+ handling in human interstitial cells of Cajal. Gastroenterology, 132, 2057–2059 (2007).PubMedCrossRefGoogle Scholar
  3. Fioramonti, J. and Bueno, L., Centrally acting agents and visceral sensitivity. Gut, 51Suppl 1, i91–i95 (2002).PubMedCrossRefGoogle Scholar
  4. Hwang, S. J., Blair, P. J., Britton, F. C., O’Driscoll, K. E., Hennig, G., Bayguinov, Y. R., Rock, J. R., Harfe, B. D., Sanders, K. M., and Ward, S. M., Expression of anoctamin1/TMEM16A by interstitial cells of Cajal is fundamental for slow wave activity in gastrointestinal muscles. J. Physiol., 587, 4887–4904 (2009).PubMedCrossRefGoogle Scholar
  5. Kim, B. J., So, I., and Kim, K. W., The relationship of TRP channels to the pacemaker activity of interstitial cells of Cajal in the gastrointestinal tract. J. Smooth Muscle Res., 42, 1–7 (2006).PubMedCrossRefGoogle Scholar
  6. Long, Y., Liu, Y., Tong, J., Qian, W., and Hou, X., Effectiveness of trimebutine maleate on modulating intestinal hypercontractility in a mouse model of postinfectious irritable bowel syndrome. Eur. J. Pharmacol., 636, 159–165 (2010).PubMedCrossRefGoogle Scholar
  7. Longstreth, G. F., Thompson, W. G., Chey, W. D., Houghton, L. A., Mearin, F., and Spiller, R. C., Functional bowel disorders. Gastroenterology, 130, 1480–1491 (2006).PubMedCrossRefGoogle Scholar
  8. Mearin, F., Badía, X., Balboa, A., Baró, E., Caldwell, E., Cucala, M., Díaz-Rubio, M., Fueyo, A., Ponce, J., Roset, M., and Talley, N. J., Irritable bowel syndrome prevalence varies enormously depending on the employed diagnostic criteria: comparison of Rome II versus previous criteria in a general population. Scand. J. Gastroenterol., 36, 1155–1161 (2001).PubMedCrossRefGoogle Scholar
  9. Morisawa, T., Hasegawa, J., Tanabe, K., Watanabe, A., Kitano, M., and Kishimoto, Y., Effects of trimebutine maleate on delayed rectifier K+ currents in guinea-pig ventricular myocytes. J. Pharm. Pharmacol., 52, 403–408 (2000).PubMedCrossRefGoogle Scholar
  10. Nagasaki, M., Kobayashi, T., and Tamaki, H., Effects of trimebutine on cytosolic Ca2+ and force transitions in intestinal smooth muscle. Eur. J. Pharmacol., 195, 317–321 (1991).PubMedCrossRefGoogle Scholar
  11. Nagasaki, M., Komori, S., and Ohashi, H., Effect of trimebutine on voltage-activated calcium current in rabbit ileal smooth muscle cells. Br. J. Pharmacol., 110, 399–403 (1993a).PubMedGoogle Scholar
  12. Nagasaki, M., Komori, S., Tamaki, H., and Ohashi, H., Effect of trimebutine on K+ current in rabbit ileal smooth muscle cells. Eur. J. Pharmacol., 235, 197–203 (1993b).PubMedCrossRefGoogle Scholar
  13. Pasricha, P. J., Desperately seeking serotonin. A commentary on the withdrawal of tegaserod and the state of drug development for functional and motility disorders. Gastroenterology, 132, 2287–2290 (2007).PubMedCrossRefGoogle Scholar
  14. Roman, F. J., Lanet, S., Hamon, J., Brunelle, G., Maurin, A., Champeroux, P., Richard, S., Alessandri, N., and Gola, M., Pharmacological properties of trimebutine and N-monodesmethyltrimebutine. J. Pharmacol. Exp. Ther., 289, 1391–1397 (1999).PubMedGoogle Scholar
  15. Sanders, K. M., Interstitial cells of Cajal at the clinical and scientific interface. J. Physiol., 576, 683–687 (2006).PubMedCrossRefGoogle Scholar
  16. Simrén, M., Brazier, J., Coremans, G., Dapoigny, M., Müller-Lissner, S. A., Pace, F., Smout, A. J., Stockbrügger, R. W., Vatn, M. H., and Whorwell, P. J., Quality of life and illness costs in irritable bowel syndrome. Digestion, 69, 254–261 (2004).PubMedCrossRefGoogle Scholar
  17. Spiller, R., Aziz, Q., Creed, F., Emmanuel, A., Houghton, L., Hungin, P., Jones, R., Kumar, D., Rubin, G., Trudgill, N., and Whorwell, P., Guidelines on the irritable bowel syndrome: mechanisms and practical management. Gut, 56, 1770–1798 (2007).PubMedCrossRefGoogle Scholar
  18. Takenaga, H., Magaribuchi, T., and Tamaki, H., Effects of trimebutine maleate (TM-906) on the spontaneous contraction of isolated duodenum and ileum in both guinea pigs and rabbits. Jpn. J. Pharmacol., 40, 13–20 (1986).PubMedCrossRefGoogle Scholar
  19. Tan, W., Zhang, H., Luo, H.-S., and Xia, H., Effects of trimebutine maleate on colonic motility through Ca2+-activated K+ channels and L-type Ca2+ channels. Arch. Pharm. Res., 34, 979–985 (2011).CrossRefGoogle Scholar
  20. Won, K. J., Sanders, K. M., and Ward, S. M., Interstitial cells of Cajal mediate mechanosensitive responses in the stomach. Proc. Natl. Acad. Sci. U. S. A., 102, 14913–14918 (2005).PubMedCrossRefGoogle Scholar
  21. Zhu, M. H., Kim, T. W., Ro, S., Yan, W., Ward, S. M., Koh, S. D., and Sanders, K. M., A Ca2+-activated Cl conductance in interstitial cells of Cajal linked to slow wave currents and pacemaker activity. J. Physiol., 587, 4905–4918 (2009).PubMedCrossRefGoogle Scholar

Copyright information

© The Pharmaceutical Society of Korea and Springer Netherlands 2011

Authors and Affiliations

  1. 1.Department of Life Science & Biotechnology, College of Natural SciencesDong-eui UniversityBusanKorea
  2. 2.Division of Longevity and Biofunctional Medicine, School of Korean MedicinePusan National UniversityYangsanKorea

Personalised recommendations