Review article: the therapeutic potential of 5-HT3 receptor antagonists in the treatment of irritable bowel syndrome.
There is evidence from studies, in both animals and humans, that 5-HT3 receptor blockade has potential value in the treatment of irritable bowel syndrome, particularly in those patients with diarrhoea-predominant bowel habits. New findings suggest that 5-HT3 receptors exist on gut afferent neurones and that their activation by locally released 5-HT leads to visceral nociceptive stimulation, in addition to increased neuronally-mediated motor and secretory activity. If this concept is validated, it will provide a rationale for the use of 5-HT3 receptor antagonists in patients with increased gut motility, reduced fluid absorption and low nociceptive thresholds leading to abdominal pain. Alosetron is a highly selective, potent 5-HT3 receptor antagonist which is well absorbed with a long pharmacodynamic half-life. Its ability to provide long-lasting blockade of 5-HT3 receptors throughout the body make it an ideal candidate within its class to evaluate the clinical hypothesis that sustained and ubiquitous 5-HT3 receptor blockade is of value in the treatment of IBS.
Humphrey
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PP
Glaxo Institute of Applied Pharmacology, Department of Pharmacology, University of Cambridge, UK. ppah0562@glaxowellcome.co.uk
Bountra
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C
Clayton
N
N
Kozlowski
K
K
D000818:Animals; D002243:Carbolines / Q000494:pharmacology / Q000627:therapeutic use*; D003109:Colonic Diseases, Functional / Q000188:drug therapy*; D006801:Humans; D007422:Intestines / Q000502:physiology; D011985:Receptors, Serotonin / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology / Q000627:therapeutic use*
D002243:Carbolines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C090840:alosetron