Alosetron relieves pain and improves bowel function compared with mebeverine in female nonconstipated irritable bowel syndrome patients

Jones, Roger; Holtmann, Gerald; Rodrigo, Luís; Ehsanullah, R. S. B.; Crompton, Philippa; Jacques, Loretta; Mills, J. G.

doi:10.1046/j.1365-2036.1999.00678.x

Cited by 117 publications

(98 citation statements)

References 26 publications

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“…Serotonin plays a crucial part in the regulation of gastro intestinal secretion, motility, perception and central nervous system function 115,116 , and several drugs used for treating functional dyspepsia target 5-HT receptors 117 (see below). In one study 118 of polymorphisms in candidate genes for different 5-HT receptors, cholecystokinin receptors and GNB3 as well as in the promoters of the genes encoding cholecystokinin and the sodium-dependent serotonin transporter, only the role of GNB3 in functional dyspepsia was confirmed.…”

Section: Genetic Contributionsmentioning

confidence: 99%

Functional dyspepsia

Enck¹,

Azpiroz

Boeckxstaens

et al. 2017

Nat Rev Dis Primers

242

247

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| Functional dyspepsia is one of the most prevalent functional gastrointestinal disorders. Functional dyspepsia comprises three subtypes with presumed different pathophysiology and aetiology: postprandial distress syndrome (PDS), epigastric pain syndrome (EPS) and a subtype with overlapping PDS and EPS features. Functional dyspepsia symptoms can be caused by disturbed gastric motility (for example, inadequate fundic accommodation or delayed gastric emptying), gastric sensation (for example, sensations associated with hypersensitivity to gas and bloating) or gastric and duodenal inflammation. A genetic predisposition is probable but less evident than in other functional gastrointestinal disorders, such as irritable bowel syndrome (IBS). Psychiatric comorbidity and psychopathological state and trait characteristics could also play a part, although they are not specific to functional dyspepsia and are less pronounced than in IBS. Possible differential diagnoses include Helicobacter pylori infection and peptic ulceration. Pharmacological therapy is mostly based on the subtype of functional dyspepsia, such as prokinetic and fundus-relaxing drugs for PDS and acid-suppressive drugs for EPS, whereas centrally active neuromodulators and herbal drugs play a minor part. Psychotherapy is effective only in a small subset of patients, whereas quality of life can be severely affected in nearly all patients. Future therapies might include novel compounds that attempt to treat the underlying gastric and duodenal inflammation. NATURE REVIEWS | DISEASE PRIMERS VOLUME 3 | ARTICLE NUMBER 17081 | 1 PRIMER © 2 0 1 7 M a c m i l l a n P u b l i s h e r s L i m i t e d , p a r t o f S p r i n g e r N a t u r e . A l l r i g h t s r e s e r v e d .standard therapy for gastro -oesophageal reflux disease. Paediatric dyspeptic symptoms are being addressed in a separate classification effort 10 . This Primer covers functional dyspepsia in adults only, although we sporadically refer to paediatric functional dyspepsia when similarities exist. EpidemiologyThe population prevalence of functional dyspepsia is quite variable across the globe, with overall high numbers (10-40%) in Western countries and low numbers (5-30%) in Asia, independent of the respective functional dyspepsia definitions 11 . A large-scale health and nutrition survey from France 12 (which involved >35,000 people) identified that 15% of individuals had suspected functional dyspepsia, 28% had irritable bowel syndrome (IBS) and 6% had both. The population of patients who are affected by both IBS and functional dyspepsia has been reported to range between 10% and 27% in previous studies 13 and to approach 30% in popu lation samples; it could be even higher in specific populations 14,15 . This observation has given rise to the term 'overlap syndrome' (REF. 13), which calls into question the sensitivity and specificity of the Rome criteria, at least for IBS and functional dyspepsia. This argument is also supported by the observation that patients with functional dyspepsia m...

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Section: Genetic Contributionsmentioning

confidence: 99%

Functional dyspepsia

Enck¹,

Azpiroz

Boeckxstaens

et al. 2017

Nat Rev Dis Primers

242

247

View full text Add to dashboard Cite

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“…Clinical phase II and III trials have demonstrated superiority of alosetron or cilansetron over placebo, and over an alternative IBS treatment (mebeverine) in one study, with respect to the specific primary endpoints used in each study [16][17][18][19][20][21][22] . However, the primary endpoints varied across studies.…”

Section: Introductionmentioning

confidence: 99%

Effects of 5-Hydroxytryptamine (Serotonin) Type 3 Antagonists on Symptom Relief and Constipation in Nonconstipated Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Andresen

Montori

Keller³

et al. 2008

Clinical Gastroenterology and Hepatology

179

141

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“…Several multicenter, randomized, placebo controlled trials (Lembo et al 1996;Jones et al 1999;Camilleri et al 2000Camilleri et al , 2001Watson et al 2001;Wolfe at al 2001) have shown that alosetron relieves pain, improves bowel function, controls bowel urgency, provides global symptom improvement and improves quality of life in women with diarrhea-predominant irritable bowel syndrome. In a randomized controlled trial of 714 patients alosetron-treated patients had signifi cantly greater 48-wk average adequate relief (p = 0.01) and urgency control (p Ͻ 0.001) rates compared with placebo.…”

Section: Alosetronmentioning

confidence: 99%

Serotonin receptor modulators in the treatment of irritable bowel syndrome

Fayyaz

Lackner

2008

TCRM

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Abstract:The aim of this article is to review the pathophysiology and clinical role of serotonin receptor modulators used in the treatment of irritable bowel syndrome. Serotonin is an important monoamine neurotransmitter that plays a key role in the initiation of peristaltic and secretory refl exes, and in modulation of visceral sensations. Several serotonin receptor subtypes have been characterized, of which 5HT3, 5HT4, and 5HT1b are the most important for GI function. 5HT4 agonists (eg, tegaserod) potentiate peristalsis initiated by 5HT1 receptor stimulation. 5HT4 agonists are therefore useful in constipation predominant form of IBS and in chronic constipation. 5HT3 antagonists (Alosetron and Cilansetron) prevent the activation of 5HT3 receptors on extrinsic afferent neurons and can decrease the visceral pain associated with IBS. These agents also retard small intestinal and colonic transit, and are therefore useful in diarrhea-predominant IBS. Tegaserod has been demonstrated in several randomized, placebo controlled trials to relieve global IBS symptoms as well as individual symptoms of abdominal discomfort, number of bowel movements and stool consistency. Several randomized, controlled trials have shown that alosetron relieves pain, improves bowel function, and provides global symptom improvement in women with diarrhea-predominant irritable bowel syndrome. However, ischemic colitis and severe complications of constipation have been major concerns leading to voluntary withdrawal of Alosetron from the market followed by remarketing with a comprehensive risk management program.

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Alosetron relieves pain and improves bowel function compared with mebeverine in female nonconstipated irritable bowel syndrome patients

Abstract: In nonconstipated female irritable bowel syndrome patients, alosetron is significantly more effective than mebeverine in improving symptoms.

Cited by 117 publications

References 26 publications

Functional dyspepsia

Functional dyspepsia

Effects of 5-Hydroxytryptamine (Serotonin) Type 3 Antagonists on Symptom Relief and Constipation in Nonconstipated Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Serotonin receptor modulators in the treatment of irritable bowel syndrome

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