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Related Experiment Videos

Serotoninergic neuroenteric modulators.

N J Talley1

  • 1Department of Medicine, University of Sydney, Nepean Hospital, PO Box 63, NSW 2751, Penrith, Australia. talleyn@wahs.nsw.gov.au

Lancet (London, England)
|January 5, 2002
PubMed
Summary
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New drugs targeting serotonin (5HT) receptors for irritable bowel syndrome (IBS) show modest benefits but face toxicity and safety concerns. Better understanding of IBS pathophysiology is needed for safer, more effective treatments.

Area of Science:

  • Gastroenterology
  • Pharmacology
  • Neurogastroenterology

Background:

  • Irritable bowel syndrome (IBS) is a prevalent and disabling gastrointestinal disorder.
  • Serotonin (5HT) and other neuroenteric modulators are key targets for IBS treatment, but toxicity has hindered progress.
  • Existing drugs targeting 5HT receptors have shown limited efficacy and significant safety concerns.

Purpose of the Study:

  • To review the efficacy and safety of neuroenteric modulators targeting serotonin receptors for IBS.
  • To discuss the challenges in developing effective and safe treatments for IBS.
  • To highlight the need for better-defined drug targets based on IBS pathophysiology.

Main Methods:

  • Review of clinical data on 5HT receptor antagonists (e.g., alosetron, cilansetron) and agonists (e.g., tegaserod, prucalopride).

Related Experiment Videos

  • Analysis of therapeutic gains over placebo and reported adverse events.
  • Discussion of the role of serotonin pathways in IBS pathophysiology.

    • Main Results:

    • 5HT(3) receptor antagonists like alosetron offer modest relief for diarrhea-predominant IBS in women but carry risks of ischemic colitis and constipation.
    • 5HT(4) receptor agonists like tegaserod show benefits in constipation-predominant IBS, primarily in women, with limited long-term data and safety concerns.
    • Development of other 5HT receptor modulators is ongoing, but significant therapeutic gains with safety remain a challenge.

    Conclusions:

    • Current neuroenteric modulators for IBS have demonstrated limited clinical benefits and significant safety concerns, necessitating careful patient selection and monitoring.
    • The development of safer and more effective IBS treatments requires a deeper understanding of the underlying pathophysiology to identify precise drug targets.
    • Future research should focus on refining therapeutic strategies and exploring novel targets beyond single serotonin receptor modulation for improved IBS management.