Skip to main content
SpringerLink
Log in

Alosetron

  • Adis New Drug Profile
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

  • ▴ Alosetron is a potent and highly selective serotonin 5-HT3 receptor antagonist which has been evaluated for the management of irritable bowel syndrome (IBS). It blocked the fast 5HT3-mediated depolarisation of guinea-pig myenteric and submucosal neurons in vitro, with half-maximal inhibition at approximately 55 nmol/L.

  • ▴ Alosetron attenuated the visceral nociceptive effect of rectal distension in conscious or anaesthetised dogs. It increased the compliance of the colon to distension in patients with IBS and delayed colonic transit in patients with IBS or carcinoid diarrhoea and in healthy volunteers.

  • ▴ A single dose of alosetron 4mg increased in vivo fluid absorption in normal human small intestine.

  • ▴ In clinical trials in patients with IBS, alosetron 1mg twice daily was effective in relieving abdominal pain and discomfort. Alosetron was most effective in female patients and particularly in those with diarrhoea-predominant IBS.

  • ▴ In patients with IBS and healthy volunteers who received alosetron, the most common adverse event was constipation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Baxendale A, Bountra C, Clayton N, et al. Irritable bowel syndrome as visceral hyperalgesia: implications for therapy? Current Opinion in Central and Peripheral Nervous System Investigational Drugs 1999; 1(1): 86–97

    CAS  Google Scholar 

  2. Drossman DA, Whitehead WE, Camilleri M, et al. Irritable bowel syndrome: a technical review for practice guideline development. Gastroenterology 1997 Jun; 112: 2120–37

    Article  PubMed  CAS  Google Scholar 

  3. Kilpatrick GJ, Hagan RM, Butler A, et al. GR68755, a potent and selective antagonist of 5-HT3 receptors [abstract]. Br J Pharmacol 1991 Oct; 104 Suppl.: 259P

    Google Scholar 

  4. Kilpatrick GJ, Hagan RM, Oxford AW, et al. GR-68755 hydrochloride. Drugs Future 1992; 17(8): 660–4

    Google Scholar 

  5. Farthing MJG. New drugs in the management of the irritable bowel syndrome. Drugs 1998 Jul; 56: 11–21

    Article  PubMed  CAS  Google Scholar 

  6. Gershon MD. Review article: roles played by 5-hydroxytryptamine in the physiology of the bowel. Aliment Pharmacol Ther 1999; 13 Suppl. 2: 15–20

    PubMed  Google Scholar 

  7. Pan H, Gershon MD. Effects of alosetron on the activation of submucosal primary afferent neurons, the peristaltic reflex, and responses of enteric neurons to 5-HT [abstract]. Gastroenterology 1999 Apr; 116 (Pt 2): 1058

    Google Scholar 

  8. Corrigan B, Lettis S, Kersey K, et al. Concentration effect relationship between alosetron and intradermal 5-HT induced flare response in volunteers following oral dosing [abstract]. PharmSci 1999; 1S: 2127

    Google Scholar 

  9. Humphrey PPA, Bountra C, Clayton N, et al. Review article: the therapeutic potential of 5-HT3 receptor antagonists in the treatment of irritable bowel syndrome. Aliment Pharmacol Ther 1999; 13 Suppl. 2: 31–8

    Article  PubMed  Google Scholar 

  10. Miura M, Lawson DC, Clary EM, et al. Central modulation of rectal distension-induced blood pressure changes by alosetron, a 5-HT3 receptor antagonist. Dig Dis Sci 1999 Jan; 44: 20–4

    Article  PubMed  CAS  Google Scholar 

  11. Delvaux M, Louvel D, Mamet J-R Effect of alosetron on responses to colonic distension in patients with irritable bowel syndrome. Aliment Pharmacol Ther 1998 Sep; 12: 849–55

    Article  PubMed  CAS  Google Scholar 

  12. Zerbib F, Bruley des Varannes, Oriola RC, et al. Alosetron does not affect the visceral perception of gastric distension in healthy subjects. Aliment Pharmacol Ther 1994 Aug; 8: 403–7

    Article  PubMed  CAS  Google Scholar 

  13. Bearcroft CP, André EA, Farthing MJG. In vivo effects of the 5-HT3 antagonist alosetron on basal and cholera toxin-induced secretion in the human jejunum: a segmental perfusion study. Aliment Pharmacol Ther 1997 Dec; 11: 1109–14

    Article  PubMed  CAS  Google Scholar 

  14. Foster JM, Houghton LA, Whorwell PJ. Alosetron slows colonic transit in patients with irritable bowel syndrome [abstract]. Gastroenterology 1997 Apr; 112 Suppl.: 732

    Google Scholar 

  15. Houghton LA, Foster J, Whorwell PJ, et al. Effect of alosetron, a new 5HT3 antagonist, on gastrointestinal transit in normal healthy volunteers [abstract]. Gastroenterology 1995 Apr; 108 Suppl.: 618

    Article  Google Scholar 

  16. Tomlin J, McDonald JN, Read NW. The effect of a 5HT3 antagonist (alosetron) on the transit of a meal and the ileal brake in man [abstract]. Gastroenterology 1994 Apr; 106 Suppl.: 579

    Google Scholar 

  17. Saslow SB, Scolapio JS, Camilleri M, et al. Medium term effects of a new 5HT3 antagonist, alosetron, in patients with carcinoid diarrhoea. Gut 1998 May; 42: 628–34

    Article  PubMed  CAS  Google Scholar 

  18. Khoury R, Peghini P, Katz P, et al. Alosetron, a new 5HT3 antagonist has no adverse effects on esophageal sphincter (LES) pressure. Gastroenterology 1998; 114 (4, Pt 2): A732

    Google Scholar 

  19. Nomura T, Evans DF, Wingate DL, et al. Alosetron, a selective 5-HT3 antagonist, does not perturb normal human small bowel motor patterns [abstract]. Gastroenterology 1998 Apr 15 (Pt 2); 114 Suppl.: 811

    Google Scholar 

  20. Hsyu PH, Pritchard JF, Lloyd TL. Safety and age, gender, and time dependent pharmacokinetics of alosetron [abstract]. Pharm Res 1995 Sep; 12 Suppl.: 387

    Article  Google Scholar 

  21. Corrigan B, Manzo J, James C, et al. The effect of repeat dosing on the pharmacokinetics of alosetron 1mg bid [abstract]. PharmSci 1998; 1: 5484

    Google Scholar 

  22. Bradbury A, Cozens SJ, Evans DC, et al. The disposition of GR 68755 after oral administration in man [abstract]. Br J Clin Pharmacol 1991 Nov; 32: 654

    Google Scholar 

  23. Andrew PD, Murkitt GS, Millson DS, et al. The determination of GR 68755 in plasma and its pharmacokinetic profile in human volunteers. Br J Clin Pharmacol 1991 Nov; 32: 667P

    Google Scholar 

  24. Gunput MD. Review article: clinical pharmacology of alosetron. Aliment Pharmacol Ther 1999; 13 Suppl. 2: 70–6

    Article  PubMed  Google Scholar 

  25. Corrigan B, Palmer J, Gillotin C, et al. The effect of food on the pharmacokinetics of alosetron [abstract]. PharmSci 1998; 1 S484

    Google Scholar 

  26. Gupta SK, Kunka RL, Metz A, et al. Effect of alosetron (a new 5-HT3 receptor antagonist) on the pharmacokinetics of haloperidol in schizophrenic patients. J Clin Pharmacol 1995 Feb; 35: 202–7

    PubMed  CAS  Google Scholar 

  27. Palmer J, Noordin N, Andrew P, et al. The effect of gender on the pharmacokinetics of alosetron [abstract]. PharmSci 1998; 1: S465

    Google Scholar 

  28. Knaggs AR, Cable KM, Cannell RJP, et al. Biotransformation of alosetron: mechanism of hydantoin formation. Tetrahedron Lett 1995; 36(3): 477–80

    Article  CAS  Google Scholar 

  29. D’Souza D, Jewell D, Ricci B, et al. Effect of alosetron (A) on the pharmacokinetics of cisapride (C), and examination of QT interval [abstract]. PharmSci 1999 Suppl. 1S: 2086

  30. Hedayetullah N, Jewell D, Willmore E, et al. Effect of alosetron on pharmacokinetics (pk) of theophylline [abstract]. Pharm Sci 1999; IS: 2483

    Google Scholar 

  31. Manzo J, Simms L, Koch K, et al. Effect of alosetron on pharmacokinetics (pk) of levonorgestrel (LN) and ethinyl estradiol (EE) [abstract]. PharmSci 1999; 1S: 2080

    Google Scholar 

  32. Bardhan KD, Bodemar G, Geldof II, et al. A double-blind, randomized, placebo-controlled dose-ranging study to evaluate the efficacy of alosetron in the treatment of irritable bowel syndrome. Aliment Pharmacol Ther 2000; 14: 23–34

    Article  PubMed  CAS  Google Scholar 

  33. Camilleri M, Mayer EA, Drossman DA, et al. Improvement in pain and bowel function in female irritable bowel patients with alosetron, a 5-HT3 receptor antagonist. Aliment Pharmacol Ther 1999; 13: 1149–59

    Article  PubMed  CAS  Google Scholar 

  34. Jones RH, Holtmann G, Rodrigo L, et al. Alosetron relieves pain and improves bowel function compared with mebeverine in female nonconstipated irritable bowel syndrome patients. Aliment Pharmacol Ther 1999; 13: 1419–27

    Article  PubMed  CAS  Google Scholar 

  35. Mangel AW, Hahn BA, Heath AT, et al. Adequate relief as an endpoint in clinical trials in irritable bowel syndrome. J Int Med Res 1998; 26: 76–81

    PubMed  CAS  Google Scholar 

  36. Mangel AW, Camilleri M, Chey WY, et al. Treatment of female IBS patients with alosetron. A potent and selective 5HT-3 receptor antagonist [abstract]. Gastroenterology 1999 Apr; 116 (Pt 2): 1036

    Google Scholar 

  37. Mangel AW, Camilleri M, Chey WY, et al. Alosetron, a 5-HT3 receptor antagonist, in the treatment of non-constipated female IBS patients [abstract]. Am J Gastroenterol 1999; 94(9): 2677

    Google Scholar 

  38. Lacey LA, McSorly D, Northcutt A, et al. Impact of alosetron on health related quality of life (HRQOL) and productivity in female patients with irritable bowel syndrome [abstract]. Gut 1999; 45 Suppl. V

  39. Watson MW, Lacey LA, McSorley D, et al. Impact of alosetron on health-related quality of life (HRQOL) in female patients with irritable bowel syndrome (IBS) [abstract]. Am J Gastroenterol 1999; 94: 2762

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Adis International Limited, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, Auckland 10, New Zealand

    Julia A. Barman Balfour, Karen L. Goa & Caroline M. Perry

Authors
  1. Julia A. Barman Balfour
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Karen L. Goa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Caroline M. Perry
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Caroline M. Perry.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Balfour, J.A.B., Goa, K.L. & Perry, C.M. Alosetron. Drugs 59, 511–518 (2000). https://doi.org/10.2165/00003495-200059030-00008

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-200059030-00008

Keywords

Search

Navigation