Conclusion - Prokinetic agents are promizing agents for the treatment of functional Bowel Disorders but until now their use was limited related to a poor prokinetic activity and side effects. Moreover, they are dedicated to selected patients according to a recognized classification such as ROME II classification for Functional Dyspepsia and Irritable Bowel Syndrome. For both syndromes about 30 to 50 % of patients may exhibit a motor defect that can be treatted by prokinetic agents. Among them, the agents targetting 5-HT receptors and particularly selective 5-HT4 receptor agonists are just entering the market with encouraging results. However, abdominal pain remains the major symptom in Functional Bowel Disorders and the efficacy of prokinetic agents on this symptom remains to be documented.


  1. P. Bytzer, Gut, 50, 58-62 (2002)
  2. M.R. Briejer and J.A. Schuurkes, Eur. J. Pharmacol., 308, 173-180 (1996)
  3. R.W. McCallum, Am. J. Gastroenterol., 86.135-149 (1991)
  4. F. De Ponti and J. Malagelada, Pharmacol. Ther., 80, 49-88 (1998)
  5. R.W. McCallum, Am. J. Med. Sei., 312,19-26 (1996)
  6. S. McHugh, S. Lico and N.E. Diamant, Dig. Dis. Sei., 37, 997-1001 (1992)
  7. M. Camilleri, J.R. Malagelada, T.L. Abel, M.L. Brown, V. Hench and A.R. Zinsmeister, Gastroenterology, 96, 704-712 (1989)
  8. R.D. Richards, G.A. Valenzuela, K.G. Davenport, K.L. Fisher and R.W. McCallum, Dig. Dis. Sei., 38, 811-816(1993)

9 L. Degen, D. Matzinger, M. Merz, S. Appel-Dingemanse, S. Osborne, S. Luchinger, R. Bertold, H. Maecke and C. Beglinger, Aliment. Pharmacol. Ther., 15,1745-1751 (2001)

  1. Y. Nagakura, S. Akuzawa, K. Miyata, T. Kamato, T. Suzuki, H. Ito and T. Yamaguchi, Pharmacol. Res., 39, 375-382 (1999)
  2. N. Haga, H. Suzuki, Y. Shiba, E. Mochiki, A. Mizumoto and Z. Itoh, Neurogastroenterol. Motil., 10, 295-303 (1998)
  3. E.P. Bouras, M. Camilleri, D.D. Burton and S. McKinzie, Gut, 44, 682-686 (1999)
  4. M N.L.eyers, J.Tack, S.Middleton, M.Horne, H.Piessevaux, J.BIoor and R. Palme, Gut, 51, A10(2002)
  5. D.J. Bill, J. Coleman, I. Hallett, V.C. Middlefell, K.F. Rhodes and A. Fletcher, Br. J. Pharmacol., 115, 775-780 (1995)
  6. J. Borovicka, C. Kreiss, K. Asal, B. Remy, C. Mettraux, A. Wells, N.W. Read, J.B. Jansen, M. d'Amato, A.B. Delaloye, M. Fried and W. Schwizer, Am. J. Physiol., 271. G448-G453 (1996)
  7. M. Katschinski, C. Dippel, M. Reinshagen, J. Schirra, R. Arnold, R. Nustede, C. Beglinger and G. Adler, Clin. Invest., 70, 902-908 (1992)
  8. J. Boulant, J. Fioramonti, M. Dapoigny, G. Bommelaer and L. Bueno, Gastroenterology, 107, 1059-1066 (1999)
  9. J. Boulant, S. Mathieu, M. D'Amato, A. Abergel, M. Dapoigny and G.Bommelaer, Gut, 40, 575-578(1997)
  10. A.S. Chua, M. Bekkering, L.C. Rovati and P.W. Keeling, Ann. N.Y. Acad. Sci., 713, 451453 (1994)
  11. M. Fried and C.Feinle, Gut, 51, 54-57 (2002)
  12. S.D. Feighner, C.P. Tan, K.K. McKee, O.C. Palyha, D.L. Hreniuk, S.S. Pong, C.P. Austin, D. Figueroa, D. MacNell, M.A. Cascieri, R. Nargund, R. Bakshi, M. Abramovitz, R. Stocco, S. Kargmab, G. O'Neil, L.H. Van Der Ploeg, J. Evans, A.A. Patchett, R.G. Smith and A.D. Howard, Science, 284,2184-2188 (1999)
  13. J.D. Chen, Z.Y. Lin, M.C. Edmunds 3"" and R.W. McCallum, Dig. Dis. Sci., 43, 80-89 (1998)
  14. M.F. Otterson and S.K Sarna, Am. J. Physiol., 259, G355-G363 (1990)
  15. J. Janssens, T. Peeters, G. Vantrappen, J. Tack, J.L. Urbain, M. De Roo, E. Muls and R..Bouillon, N. Engl. J. Med., 322,1028-1031 (1990)
  16. K. Maganti, K. Onyemere and M.P. Jones, Am. J. Gastroenterol., 98, 259-263 (2003)
  17. B. Coule, J. Tack, T. Peeters and J. Janssens, Gut, 43,395-400 (1998)
  18. J.K. DiBaise and E.M. Quigley, J. Clin. Gastroenterol., 28,131-134 (1999)
  19. T. Tanaka, A. Mizumoto, E. Mochiki, H. Suzuki, Z. Itoh and S. Omura, J. Pharmacol. Exp. Ther., 287, 712-719(1998)
  20. H. Matsunaga, M. Tanaka, G. Naritomi, K. Yokohata, K. Yamagtuchi and K. Chijiwa, Ann. Surg-227. 507-512 (1998)
  21. F. Lechin and B. Van Der Dijs, J. Clin. Pharmacol., 19,617-625 (1979)
  22. C.A. Edwards, S. Holden, C. Brown and N.W. Read, Gut, 28,13-16 (1987)
  23. B. Krevski, A.H. Maurer, L.S. Malmud and R.S. Fisher, Am. J. Gastroenterol., 84. 882-887 (1989)
  24. G. Reboa, G. Amulfo, M. Frascio, C. Di Somma, G. Pitto and E. Berti-Riboli, Eur. J. Clin. Pharmacol., 26, 745-748 (1984)
  25. Farup P.G., N. Howdenak, S. Wetterhus, O.J. Lange, O. Howde and R.Trondstad, Scand. J. Gastroenterol., 33,128-131 (1998)
  26. K. Schutze, G. Brandstatter, B. Dragosics, G. Judmaier and E. Hentshel, Aliment. Pharmacol. Ther., H, 387-394 (1997)
  27. L.J. Scott and C.M. Perry, Drugs, 58,491-496 (1999)
  28. M.D. Drici, S.N. Ebert, W.X. Wang, I. Rodriguez, X.K. Liu, B.H. Witfield and R.L. Woosley, J. Cardiovasc. Pharmacol., 34. 82-88 (1999)
  29. N.H. Prins, J.F. Van Haselen, R.A. Lefebvre, M.R. Briejer, L.M. Aklermans and J.A. Schuukes, Br. J. Pharmacol., 127,1431-1437 (1999)
  30. B.Y. De Winter, G.E. Boeckxstaens, J.G. De Man, T.G. Moreels, J.A. Schuukes, T.L. Peeters, A.G. Herman and P.A. Pelckmans, Gut, 45, 713-718 (1999)
  31. J. Fioramonti, L. Bueno and M.J. Fargeas, Life Sci., 36.2509-2514 (1985)
  32. M. Liberge, M.P. Amuebo and L. Bueno, Gastroenterology, IflO. 441-449 (1991)
  33. B.M. Meyer, C. Beglinger, J.B.M.J. Jansens, L. Rovati, B.A. Werth and P. Hildebrand, Lancet, 1,12-15(1989)
  34. Barrow, P.E. Blackshaw, C.G. Wilson, L. Rovati and R.C. Spiller, Eur. J. Gastroenterol. Hepato., 6, 381-387 (1994)
  35. M. D'Amato, P.J. Whorwell, D.G. Thompson, R.C. Spiller, G. Giacovelli and L. C. Rovati, Gastroenterology, U6, A981 (1999)

Chapter 11. Urotensin-ll Receptor Modulators

Dashyant Dhanak, Michael J. Neeb and Stephen A. Douglas GlaxoSmithKline Pharmaceuticals King of Prussia, PA 19406-0939

Introduction - Human urotensin-ll, 1_, a cyclic undecapeptide was first isolated as the corresponding piscine analog in the 1960's from a vestigial organ in teleost fish (1) where it has been proposed to be involved primarily in osmoregulation (2 - 4). Subsequent efforts have led to the identification of urotensin-ll (U-ll) isoforms from a variety of species including frog, mouse, rat, pig, monkey and human (5 -10).

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Herbal Remedies For Acid Reflux

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