Drugs acting on serotonin receptors for the treatment of functional GI disorders.

Abstract

In the gut, serotonin (5-hydroxytryptamine: 5-HT) exerts a variety of effects on intrinsic enteric neurons, extrinsic afferents, enterocytes and smooth muscle cells, which are related to the expression of multiple 5-HT receptor types and subtypes regulating motility, vascular tone, secretion and perception. Agonists and antagonists at 5-HT receptors have gained access to the market for the two major variants of the irritable bowel syndrome (IBS), a functional disorder characterized by abdominal pain associated with diarrhea and/or constipation in the absence of any organic abnormality. Indeed, the 5-HT3 receptor antagonist alosetron is available in the US market for the treatment of women with severe, diarrhea-predominant IBS (D-IBS) refractory to conventional therapy, whereas tegaserod, a partial 5-HT4 receptor agonist, has been approved by the FDA and other regulatory agencies for the treatment of women with constipation-predominant IBS (C-IBS) or functional constipation. This review is mainly intended to discuss the role of non-neuronal (paracrine) and neuronal 5-HT in the pathophysiology of functional gastrointestinal disorders (FGIDs), such as IBS and functional dyspepsia, and the mechanisms through which drugs acting on 5-HT receptors regulate visceral motility, perception and secretion in these two conditions.

• Authors: Marcello Tonini, Fabio Pace
• Journal: Digestive diseases (Basel, Switzerland) (Dig Dis) Vol. 24 Issue 1-2 Pg. 59-69 ( 2006) ISSN: 0257-2753 [Print] Switzerland
• PMID: 16699264 (Publication Type: Journal Article, Review)
• Copyright: Copyright 2006 S. Karger AG, Basel.

Chemical References

• Receptors, Serotonin
• Serotonin Antagonists

Topics

• Gastrointestinal Diseases (drug therapy, metabolism, physiopathology)
• Gastrointestinal Motility (drug effects)
• Humans
• Receptors, Serotonin (drug effects, metabolism)
• Serotonin Antagonists (therapeutic use)
• Treatment Outcome