Efficacy and safety of alosetron in women with irritable bowel syndrome: a randomised, placebo-controlled trial

Camilleri, Michael; Northcutt, Allison R.; Kong, S; Dukes, George E.; McSorley, David; Mangel, Allen W.

doi:10.1016/s0140-6736(00)02033-x

Cited by 507 publications

(400 citation statements)

References 20 publications

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“…Approval of this medication was based on several large randomized controlled-trials that found alosetron (1 mg po twice daily) was more effective than placebo in controlling abdominal pain and discomfort in IBS-D [40][41][42][43] . Alosetron was associated with a statistically significant decrease in the percentage of days with urgency, and it led to firmer stools and a decrease in stool frequency.…”

Section: -Ht3 Antagonistsmentioning

confidence: 99%

Updates on treatment of irritable bowel syndrome

Hammerle¹,

Surawicz²

2008

WJG

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Irritable bowel syndrome (IBS) is a highly prevalent gastrointestinal disorder characterized by abdominal pain and discomfort in association with altered bowel habits. It is estimated to affect 10%-15% of the Western population, and has a large impact on quality of life and (in)direct healthcare costs. IBS is a multifactorial disorder involving dysregulation within the brain-gut axis, and it is frequently associated with gastrointestinal motor and sensory dysfunction, enteric and central nervous system irregularities, neuroimmune dysregulation, and postinfectious inflammation. As with other functional medical disorders, the treatment for IBS can be challenging. Conventional therapy for those with moderate to severe symptoms is largely unsatisfactory, and the development of new and effective drugs is made difficult by the complex pathogenesis, variety of symptoms, and lack of objective clinical findings that are the hallmark of this disorder. Fortunately, research advances over the past several decades have provided insight into potential mechanisms responsible for the pathogenesis of IBS, and have led to the development of several promising pharmaceutical agents. In recent years there has been much publicity over several of these new IBS medications (alosetron and tegaserod) because of their reported association with ischemic colitis and cardiovascular disease. While these agents remain available for use under restricted prescribing programs, this highlights the need for continued development of safe and effective medication for IBS. This article provides a physiologicallybased overview of recently developed and frequently employed pharmaceutical agents used to treat IBS, and discusses some non-pharmaceutical options that may be beneficial in this disorder.

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Section: -Ht3 Antagonistsmentioning

confidence: 99%

Updates on treatment of irritable bowel syndrome

Hammerle¹,

Surawicz²

2008

WJG

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“…This study also suggests that this drug is more effective in homozygous patients than in heterozygous patients for 5-HTTLPR insertion. However, the small number of patients enrolled in this study does not permit a firm conclusion [23,24] .…”

Section: Serotonin Polymorphismsmentioning

confidence: 77%

Genetic determination of irritable bowel syndrome

Hotoleanu¹,

Popp²,

Trifa³

et al. 2008

WJG

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Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder. According to the Rome Ⅲ criteria, IBS is defined as recurrent abdominal pain or discomfort for at least 3 d per month during the previous 3 mo associated with two or more of the following symptoms: improvement with defecation, onset associated with a change in the frequency of stool and/or onset associated with a change in form or appearance of stool. There is growing evidence regarding the genetic contribution in IBS, however the precise etiology of IBS is still unknown. The evaluation of the genetic influence is based on twin studies, familial aggregation and genetic epidemiological investigations. Most studies showed a concordance for IBS significantly greater in monozygotic than in dizygotic twins. The majority of the studies have shown that familial aggregation may represent exposures to a similar environment, as well as the influence of genetic factors. Whereas no specific gene has been identified in association with IBS, recent studies have noticed the importance of polymorphisms in the promoter region of the serotonin reuptake transporter gene, G-protein beta 3 subunit gene (C825T ), cholecystokinin receptor (CCKAR gene 779T>C), and high-producer tumor necrosis factor genotype. Further studies are necessary to determine how genetic factors influence the clinical manifestations and therapeutical response in IBS patients.

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“…One of the serotonergic receptors belongs to the 5-HT3 receptor subtype [50] .Efficacy of blockade of 5-HT3 receptors by a 5-HT3 antagonist in the treatment of diarrhea in the diarrhea-predominant population of women with IBS [51,52] suggests that hyperstimulation of secretomotor neurons by serotonin is a significant factor in this form of IBS. Observations that IBS symptoms of cramping abdominal pain, diarrhea and fecal urgency are commonly exacerbated in the postprandial state [7,53] and evidence for elevated postprandial release of serotonin [54,55] suggests that overactive release of serotonin from the enterochromaffin cell population might underlie the diarrheal symptoms of IBS.…”

Section: Excitatory Input To Secretomotor Neuronsmentioning

confidence: 99%

Neuropathophysiology of functional gastrointestinal disorders

Wood

2007

WJG

101

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The investigative evidence and emerging concepts in neurogastroenterology implicate dysfunctions at the levels of the enteric and central nervous systems as underlying causes of the prominent symptoms of many of the functional gastrointestinal disorders. Neurogastroenterological research aims for improved understanding of the physiology and pathophysiology of the digestive subsystems from which the arrays of functional symptoms emerge. The key subsystems for defecation-related symptoms and visceral hypersensitivity are the intestinal secretory glands, the musculature and the nervous system that controls and integrates their activity. Abdominal pain and discomfort arising from these systems adds the dimension of sensory neurophysiology. This review details current concepts for the underlying pathophysiology in terms of the physiology of intestinal secretion, motility, nervous control, sensing function, immuno-neural communication and the brain-gut axis.

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Efficacy and safety of alosetron in women with irritable bowel syndrome: a randomised, placebo-controlled trial

Cited by 507 publications

References 20 publications

Updates on treatment of irritable bowel syndrome

Updates on treatment of irritable bowel syndrome

Genetic determination of irritable bowel syndrome

Neuropathophysiology of functional gastrointestinal disorders

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