Rationale for using serotonergic agents to treat irritable bowel syndrome.
OBJECTIVE
The role of serotonin in gastrointestinal (GI)-tract functioning, the pharmacologic rationale for using serotonergic agents in the treatment of irritable bowel syndrome (IBS), and clinical experience with novel serotonergic agents are described.


CONCLUSIONS
IBS is a common multisymptom disorder that is associated with a high socioeconomic burden. The goal of treatment is to provide rapid and sustained global relief of the multiple symptoms of IBS with a single, effective, well-tolerated agent. Traditional treatment options target single symptoms, and many patients are dissatisfied with the level of relief achieved and adverse effects. Research has revealed that serotonin is involved in three major actions in the gut: (1) mediating intestinal motility, (2) mediating intestinal secretion in the GI tract, and (3) modulating perception in the bowels. Serotonin is also a vital link in the brain-gut axis. Alterations in key elements of serotonin signaling have been demonstrated in patients with IBS. Tegaserod, a selective serotonin type 4 (5-HT(4))-receptor partial agonist, is indicated for use in women with IBS whose primary bowel symptom is constipation. Alosetron, a 5-HT(3)-receptor antagonist, is indicated for use in women with severe diarrhea-predominant IBS in whom traditional therapies have failed. The clinical usefulness of several other serotonergic agents for IBS is being investigated.


CONCLUSIONS
The use of serotonergic agents in patients with IBS is based on the critical role that serotonin plays in the maintenance of normal gut function and brain-gut communication. Pharmacologic therapies targeting specific serotonin receptors represent an important step in the management of IBS.
Baker
Danial E
DE
College of Pharmacy, Washington State University, P.O. Box 1495, Spokane, WA 99210-1495, USA. bakerdan@wsu.edu
D000818:Animals; D002986:Clinical Trials as Topic; D017615:Enteric Nervous System / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology; D012701:Serotonin / Q000502:physiology; D018490:Serotonin Agents / Q000627:therapeutic use*
D018490:Serotonin Agents; D012701:Serotonin