Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022104 (irritable bowel syndrome)
 8,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The treatment of irritable bowel syndrome with constipation (IBS-C) has historically been based on the severity of symptoms, with education, reassurance, dietary advice, bulking agents and laxative therapy offered as appropriate. Tegaserod (Zelnorm, Zelmac) is the first selective serotonin 5-HT(4) receptor partial agonist to be approved for the treatment of this syndrome. Tegaserod is active against multiple irritable bowel syndrome (IBS) symptoms; it stimulates gut motility and reduces visceral sensitivity and pain. The drug does not cure IBS and was not designed to treat the diarrhoea-predominant version. Its efficacy in men has not been established. Three large well designed clinical trials of tegaserod 6 mg twice daily for 12 weeks in patients (mainly women) with IBS-C have demonstrated superiority versus placebo in global relief from symptoms. Global relief response rates were 38.4-46.8% with tegaserod 6 mg twice daily and 28.3-38.8% with placebo (p < 0.05-0.0001 vs placebo). The relative increases in response rates with tegaserod 6 mg twice daily over the already high responses in the placebo groups ranged from 12-65% after 4-12 weeks of treatment. A response was seen within the first week. The proportion of patients with satisfactory relief from symptoms fell over the 4-week period following withdrawal of tegaserod and placebo, but did not reach baseline levels during this time. Diarrhoea has been associated with tegaserod in clinical trials (an incidence of about 10% versus 5% with placebo, usually occurring in the first week of treatment), but the drug is otherwise well tolerated. There were no apparent changes in the tolerability profile with extended tegaserod treatment (</=12 months). In conclusion, oral tegaserod 6 mg twice daily for 12 weeks is effective and well tolerated in the treatment of IBS-C in women. Data on long term and comparative efficacy, cost-effectiveness and quality-of-life effects would be beneficial; however, in light of the fact that very few alternatives for the treatment of IBS-C have proven efficacy, tegaserod appears to be a promising option in women not responding to increased dietary fibre or osmotic laxative therapy.
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PMID:Tegaserod: a review of its use in the management of irritable bowel syndrome with constipation in women. 1274 44

This was an exploratory study of renzapride in 168 male and female patients with non-D, non-C irritable bowel syndrome (IBS). Patients were randomized to placebo or renzapride (1, 2, or 4 mg/day) for 8 weeks. The primary efficacy variable was patient-reported satisfactory relief of IBS symptoms. Secondary variables included relief of abdominal pain/discomfort. The proportion of patients reporting satisfactory relief of their IBS symptoms for at least 50% of the time did not differ significantly from those on placebo. However, post hoc analysis in women showed differences in responder rate on renzapride versus placebo of 18.2% (95% CI -5% to 42%; P = 0.066) during weeks 1-4 and 6% (95% CI -21% to 33%; P = 0.339) during weeks 5-8. Renzapride was well tolerated and most adverse events were mild to moderate in intensity. Further studies are warranted to determine whether renzapride is beneficial in this patient population.
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PMID:Identification of patients with non-d, non-C irritable bowel syndrome and treatment with renzapride: an exploratory, multicenter, randomized, double-blind, placebo-controlled clinical trial. 1846 39

Renzapride is a novel drug currently under clinical evaluation for the treatment of irritable bowel syndrome (IBS). Renzapride is a mixed 5-hydroxytryptamine type 4 (5-HT4) agonist and 5-HT3 receptor antagonist that has a stimulatory effect on gastrointestinal motility and transit, as established by in vivo and in vitro studies. Its therapeutic efficacy, tolerability and safety have been evaluated in diabetic gastroparesis in a single study, as well as in IBS in a few other studies. Phase II studies indicated potential beneficial effects on symptoms and bowel habits in patients with constipation-predominant IBS and mixed-type IBS. The outcome of Phase III studies is currently under evaluation.
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PMID:Renzapride: a new drug for the treatment of constipation in the irritable bowel syndrome. 1892 3

The diagnosis of irritable bowel syndrome (IBS) frequently is made after the exclusion of a mechanical etiology for a patient's symptoms. This case demonstrates that IBS symptoms can be caused by a rare complication of a common surgery: mesh herniorrhaphy repair. The patient is a 50-year-old woman who underwent periumbilical Marlex mesh herniorrhaphy 13 years before presentation. After her operation, the patient developed constipation (approximately one bowel movement per week) alternating with diarrhea for approximately 10 years. An abdominal radiograph showed large amounts of stool, and after a normal colonoscopy the patient was diagnosed with IBS. The patient was treated with tegaserod (Zelnorm) and polyethylene glycol (MiraLAX), which did not palliate her symptoms. The patient presented with obstructive symptoms and physical findings of an incarcerated umbilical hernia. A computed tomography (CT) scan of the abdomen confirmed an umbilical hernia involving a segment of small bowel with surrounding fecalization of enteric contents. During operative repair, the patient was found to have Marlex mesh fully eroded into the lumen of the small bowel, causing a partial obstruction. The involved section of small bowel was resected, and during serial follow-up the patient had complete resolution of her IBS-like symptoms. A discussion follows regarding the implications of mesh migration, and questions are posed for future research.
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PMID:Irritable bowel syndrome: a "mesh" of a situation. 2257 Apr 6

The Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) signaling pathway plays central roles in cancer cell growth and survival. Drug repurposing strategies have provided a valuable approach for developing antitumor drugs. Zelnorm (tegaserod maleate) was originally designed as an agonist of 5-hydroxytryptamine 4 receptor (5-HT4R) and approved by the FDA for treating irritable bowel syndrome with constipation (IBS-C). Through the use of a high-throughput drug screening system, Zelnorm was identified as a JAK/STAT3 signaling inhibitor. Moreover, the inhibition of STAT3 phosphorylation by Zelnorm was independent of its original target 5-HT4R. Zelnorm could cause G1 cell cycle arrest, induce cell apoptosis and inhibit the growth of a variety of cancer cells. The present study identifies Zelnorm as a novel JAK/STAT3 signaling inhibitor and reveals a new clinical application of Zelnorm upon market reintroduction.
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PMID:Zelnorm, an agonist of 5-Hydroxytryptamine 4-receptor, acts as a potential antitumor drug by targeting JAK/STAT3 signaling. 3108 23