Irritable bowel syndrome diarrhea-predominant

Viramontes, B. E., Camilleii, M., McKinzie, S., Pardi, D. S., Burton, D., and Thomforde, G. M. (2001) Gender-related differences in slowing colonic transit by a 5-HT3 antagonist in subjects with diarrhea-predominant irritable bowel syndrome. Am. J. Gastroenterol. 96, 2671-2676. 

CamiUeri, M., Atanasova, E., Carlson, P. J., et al. (2002) Serotonin-transporter polymorphism. Pharmacogenetics in diarrhea-predominant irritable bowel syndrome. Gastroenterology. 123, 425 32. 

Only physicians who have enrolled in GlaxoSmithKline s Prescribing Program for Lotronex, based on their attestation of qualifications and acceptance of responsibilities, should prescribe alosetron (see Administration and Dosage). Alosetron is indicated only for women with severe diarrhea-predominant irritable bowel syndrome (IBS) who have failed to respond to conventional... 

Caldarella MR Milano A, Laterza F et al. Visceral sensitivity and symptoms in patients with constipation- or diarrhea-predominant irritable bowel syndrome (IBS) effect of a low-fat intraduodenal infusion. Am J Gastroenterol 2005 100(2) 383-9. 

Alosetron currently is approved for the treatment of women with severe irritable bowel syndrome in whom diarrhea is the predominant symptom ("diarrhea-predominant IBS"). Efficacy in men has not been established. In a dosage of 1 mg once or twice daily, it reduces IBS-related lower abdominal pain, cramps, urgency, and diarrhea. Approximately 50-60% of patients report adequate relief of pain and discomfort compared with 30-40% of patients treated with placebo. It also leads to a reduction in the mean number of bowel movements per day and improvement in stool consistency. This agent has not been evaluated for the treatment of other causes of diarrhea. 

Women had significantly greater responses than men. Constipation was the most commonly reported adverse effect of alosetron (49% compared with 13% in the placebo group). In a randomized, double-blind, placebo-controlled trial in 626 women with diarrhea-predominant irritable bowel syndrome, alosetron 1 mg bd was significantly more effective than placebo in controlling symptoms... 

Camilleri M, Chey WY, Mayer EA, Northcutt AR, Heath A, Dukes GE, McSorley D, Mangel AM. A randomized controlled clinical trial of the serotonin type 3 receptor antagonist alosetron in women with diarrhea-predominant irritable bowel syndrome. Arch Intern Med 2001 161(14) 1733-40. 

Lotronex is used for severe diarrhea-predominant irritable bowel syndrome (IBS). 

From a series of 1,7-annelated indole derivatives, cilansetron [(-)-162j was selected for further pharmacologicalprofilingboth in vitro and in vivo (Table 14.14) (454). In the RVN and Gpl, cilansetron [pA, 9.94 (RVN) 7.80 (Gpl)] is about 10-fold more potent than ondansetron [pA, 8.99 (RVN) 6.80 (Gpl)]. In the von Bezold-Jarisch reflex test (BJR) in unrestrained conscious rats, cilansetron (ED = 26 jLLg/kg, p.o.) is orally active at a dose 6 times lower than that of ondansetron (ED =165 ptg/kg, p.o.). Solvay announced Phase III studies for cilansetron for the treatment of diarrhea-predominant irritable bowel syndrome, in July 2001 (455). 

Alosetron was approved for U. S. use in February 2000 for the treatment of irritable bowel syndrome (IBS) in women whose predominant bowel symptom is diarrhea, although the product was withdrawn in November 2001 because of serious side effects, particularly ischemic colitis. Earlier studies in men for anxiety disorder and schizophrenia, and Phase II studies for nonulcer dyspepsia, have also been discontinued. 

Irritable bowel syndrome presents as either diarrhea-predominant or constipation-predominant disease and can be defined as lower abdominal pain, disturbed defecation (constipation, diarrhea, or an alternating pattern of both), and bloating in the absence of structural or biochemical factors that might explain these symptoms (Table 36-10). 

Bearcroft CP, Perrett D, Farthin MJG. Postprandial plasma 5-hydroxytryptamine in diarrhea predominant irritable bowel syndrome A pilot study. Gut 1988 42 42-46. 

Kim HJ, Camilleri M, McKinzie S, et al. A randomized controlled trial of a probiotic, VSL 3, on gut transit and symptoms in diarrhea-predominant irritable bowel syndrome. AUment Pharmacol Ther 2003 17 895— 904. 

The FDA has reapproved alosetron for diarrhea-predominant irritable bowel syndrome under a limited distribution system. The manufacturer requires a prescription program that includes physician certification and an elaborate patient education and consent before dispensing. 

Alosetron, another 5-HT3 antagonist, has been used for the management of severe diarrhea-predominant irritable bowel syndrome (IBS) in women only. Unlike ondansetron, it is not approved as an antiemetic. As 5-HT3 receptor stimulation enhances gastrointestinal motility, 5-HT3 antagonism with alosetron reduces the movement of fecal matter through the large intestine, thus relieving IBS. 

Tamaoki, S., Yamauchi, Y, Nakano, Y, Sakano, S., Asagarasu, A. and Sato, M. 2007. Pharmacological properties of 3-amino-5,6,7,8-tetrahydro-2- 4-[4-(quinolin-2-yl) piperazin-l-yl]butyl quinazolin-4(3//)-one (TZB-30878), a novel therapeutic agent for diarrhea-predominant irritable bowel syndrome (IBS) and its effects on an experimental IBS model. J. Pharm. Exp. Ther. 322 1315-1323. 

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