Drugs acting on serotonin receptors for the treatment of functional GI disorders.
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.
Tonini
Marcello
M
Department of Physiological and Pharmacological Sciences, University of Pavia, Pavia, Italy. tonini@unipv.it
Pace
Fabio
F
D005767:Gastrointestinal Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D005769:Gastrointestinal Motility / Q000187:drug effects; D006801:Humans; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D012702:Serotonin Antagonists / Q000627:therapeutic use*; D016896:Treatment Outcome
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists