Modulation of Serotoninergic Pathways for Treatment of Irritable Bowel Syndrome

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2007 (EN)
Modulation of Serotoninergic Pathways for Treatment of Irritable Bowel Syndrome (EN)

., M. Delvaux

SUMMARY The gut constitutes the main reservoir of the body’s serotonin. The latter has effects not only on colonic motility via activation of cholinergic or nitric oxide-dependent neurons but also on the modulation of sensation by excitation of intrinsic sensory neurons. The abundance of serotonin receptors within the enteric nervous system constituted a challenge, as the pharmacological intervention on these receptors could be the etiological treatment of Irritable Bowel Syndrome (IBS). 5-HT3 and 5-HT4 are the main subtypes of serotonin receptors in the gut. Therapeutic blockade of 5- HT3 by alosetron in women with diarrhea- predominant IBS brought a revolution in the treatment of IBS. This drug acts both on colonic motility and the secretory function of the bowel but, despite the spectacular results, it had to be withdrawn due to 49 cases of ischemic colitis. 5-HT4 agonists have been used for the treatment of patients with constipation- prone IBS. In large comparative trials tegaserod was more effective than placebo although the therapeutic gain over placebo was small. Prucalopride is a potent 5-HT4 agonist but much concern has been raised by the report of carcinogenicity in animals. Other serotonergic modulators include piboserod (SB207266) and MKC 733 but no clinical trials in humans are available. Sumatriptan, a 5-HT1B/D agonist developed for the treatment of migraine, causes relaxation of the gastric fundus in man, but its intranasal administration limits its use. As abdominal pain constitutes the main complaint of IBS patients, future efforts must concentrate on medications acting on visceral hypersensivity. Key words: Alosetron, colonic motility ivisceral hypersensivity ischemic coliti (EN)




Hellenic Society of Gastroenterology (EN)

Annals of Gastroenterology; Volume 15, No 3 (2002) (EN)

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