Drugs Acting on Serotonin Receptors for the Treatment of Functional GI DisordersTonini M. · Pace F.
aDepartment of Physiological and Pharmacological Sciences, University of Pavia, Pavia, and bDivision of Gastroenterology, ‘L. Sacco’ University Hospital, Milan, Italy
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.
Prof. Marcello Tonini
Department of Physiological and Pharmacological Sciences, University of Pavia
Piazza Botta, 11
IT–27100 Pavia (Italy)
Tel. +39 0382 986 381/4, Fax +39 0382 986 385, E-Mail firstname.lastname@example.org
Number of Print Pages : 11
Number of Figures : 2, Number of Tables : 2, Number of References : 86
Digestive Diseases (Clinical Reviews)
Vol. 24, No. 1-2, Year 2006 (Cover Date: May 2006)
Journal Editor: Malfertheiner, P. (Magdeburg)
ISSN: 0257–2753 (print), 1421–9875 (Online)
For additional information: http://www.karger.com/DDI