A Randomized Controlled Clinical Trial of the Serotonin Type 3 Receptor Antagonist Alosetron in Women With Diarrhea-Predominant Irritable Bowel Syndrome

Camilleri, Michael; Chey, William Y.; Mayer, Emeran A.; Northcutt, Allison R.; Heath, Amy; Dukes, George E.; McSorley, David; Mangel, Allen

doi:10.1001/archinte.161.14.1733

Cited by 276 publications

(206 citation statements)

References 40 publications

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“…Patient selection based on other criteria, such as bowel habit and gender, has already been shown to be of great importance for the outcome of clinical trials evaluating the efficacy of several contemporary compounds for IBS, for example alosetron and tegaserod. 23,24 Our study indicates that until clear criteria or alternative methods have been established to select individual hypersensitive patients, evaluation of perceptual thresholds to gut distension is still required. We perceive that such an approach would be very demanding if not impossible in large scale clinical trials.…”

Section: Discussionmentioning

confidence: 99%

Relationship between symptoms and hypersensitivity to rectal distension in patients with irritable bowel syndrome

Kuiken¹,

Lindeboom

Tytgat³

et al. 2005

Aliment Pharmacol Ther

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SUMMARYBackground: Visceral hypersensitivity is considered an important pathophysiological mechanism in irritable bowel syndrome, yet its relationship to symptoms is unclear. Aim: To detect possible associations between symptoms and the presence of hypersensitivity to rectal distension in patients with irritable bowel syndrome. Methods: Ninety-two irritable bowel syndrome patients and 17 healthy volunteers underwent a rectal barostat study. The association between specific irritable bowel syndrome symptoms and the presence of hypersensitivity was examined using Area under the Receiver Operating Characteristic curves. Results: Irritable bowel syndrome patients had significantly lower thresholds for discomfort/pain than healthy volunteers: 24 (18-30) and 30 (27-45) mmHg above minimal distending pressure, respectively. Forty-

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Section: Discussionmentioning

confidence: 99%

Relationship between symptoms and hypersensitivity to rectal distension in patients with irritable bowel syndrome

Kuiken¹,

Lindeboom

Tytgat³

et al. 2005

Aliment Pharmacol Ther

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show abstract

“…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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“…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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A Randomized Controlled Clinical Trial of the Serotonin Type 3 Receptor Antagonist Alosetron in Women With Diarrhea-Predominant Irritable Bowel Syndrome

Abstract: Alosetron hydrochloride, 1 mg twice daily for 12 weeks, is effective in relieving pain and some bowel-related symptoms in diarrhea-predominant female patients with IBS.

Cited by 276 publications

References 40 publications

Relationship between symptoms and hypersensitivity to rectal distension in patients with irritable bowel syndrome

Relationship between symptoms and hypersensitivity to rectal distension in patients with irritable bowel syndrome

Updates on treatment of irritable bowel syndrome

Neuropathophysiology of functional gastrointestinal disorders

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