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Query: UMLS:C0022104 (irritable bowel syndrome)
 8,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Irritable bowel syndrome (IBS) is a functional disorder of the gastrointestinal tract, characterised by abdominal pain and change in bowel habit, with a fluctuating natural history. The exact etiology remains unknown, but it is unlikely there is a single unifying explanation. The prevalence in the general population is between 5% and 20%, and the condition represents a considerable financial burden to the health service. Guidelines for the management of IBS recommend that symptom-based diagnostic criteria should be used to make a positive diagnosis, without the need for recourse to investigations to exclude organic disease. However, current evidence demonstrates that these have either not been well-validated in prospective studies or perform suboptimally. Investigations to exclude underlying organic disease in IBS have a low yield, and the diagnosis is unlikely to be revised during extended follow-up, although screening for celiac disease with serology appeared to be of value in a recent systematic review and meta-analysis, Despite the fact that no therapy is established to alter the natural history of IBS, a series of systematic reviews and meta-analyses, conducted to inform the American College of Gastroenterology's updated monograph on IBS, have demonstrated that fibre, antispasmodics, antidepressants, psychological therapies, 5-HT3 antagonists, 5-HT4 agonists, and probiotics are all more effective than placebo. Anti-diarrheal agents may be of some benefit, in terms of improved stool frequency and consistency in diarrhea-predominant IBS, and lubiprostone may have a role in constipation-predominant IBS, though data for this drug are preliminary at present.
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PMID:Management of irritable bowel syndrome. 1982 84

The functional gastrointestinal diseases (FGIDs) are often noticed disturbances. Functional dyspepsia (FD) is the most frequent FGID of the upper part of the gastrointestinal tract while irritable bowel syndrome (IBS) occurs in the lower gastrointestinal part. Both clinical entities are characterized by rich symptomatology and the pattern of the diagnostic guidelines. Recognition and the classification of FGIDs are difficult, consisting in exclusion of all possible organic disorders and subordinating on the predominant symptom basis to most appropriate class, acording to Rome III classification. The present FGIDs pharmacotherapy is limited mostly to the symptomatical treatment and it is based on medicines conventionally used in various gastrointestinal organic illnesses (antisecretory, gastroprotective agents, antidiarrhoeal and laxative drugs). Some of them which seem to diminish visceral hypersensitivity acting via serotonin receptors are also used, including 5-HT4 agonists and 5-HT3 antagonists. Many investigations over the new causal acting medicines last at present, which would be able to abolish the main pathophysiological FD and IBS mechanisms: visceral hypersensitivity and both myoelectrical and dysmotility phenomena. Thus, new pharmacological agents influencing opioid, purinergic, NMDA, CCK-A, or NK receptors are studied. The article is the mini-review, representing classification and the outline of the FGIDs pathogenesis, the present concepts of their pharmacological treatment and the future perspectives of pharmacoherapy with the use of new, interfering into key pathomechanisms drugs.
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PMID:Pathophysiological concepts of functional dyspepsia and irritable bowel syndrome future pharmacotherapy. 1989 40

The review deals with the serotoninergic regulation of colonic motor function. Serotonin (HT), its receptors and transporter, the enzymes of synthesis and degradation, play an important role in the regulation of colonic motor activity. Activation of 5-HT1, 5-HT2B, 5-HT3, and 5-HT4 receptors leads to increased colonic motor function. The elevation of serotonin levels determines the higher sensitivity of the colonic wall in irritable bowel syndrome. Serotonin plays a pathogenetic role in the development of ulcerative colitis and colostasis.
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PMID:[Serotoninergic regulation of colonic motor function]. 2365 47

5-HT4 receptor antagonists have been suggested to have clinical potential in treatment of atrial fibrillation, diarrhea-prone irritable bowel syndrome and urinary incontinence. Recently, the use of 5-HT4 antagonists has been suggested to have a therapeutic benefit in heart failure. Affinity for the hERG potassium ion channel and increased risk for prolonged QT intervals and arrhythmias has been observed for several 5-HT4 ligands. Serotonin may also have beneficial effects in the central nervous system (CNS) through stimulation of the 5-HT4 receptor, and reduced distribution of 5-HT4 antagonists to the CNS may therefore be an advantage. Replacing the amide and N-butyl side chain of the 5-HT4 receptor antagonist SB207266 with an ester and a benzyl dimethyl acetic acid group led to compound 9; a hydrophilic 5-HT4 antagonist with excellent receptor binding and low affinity for the hERG potassium ion channel. To increase oral bioavailability of carboxylic acid 9, two different prodrug approaches were applied. The tert-butyl prodrug 11 did not improve bioavailability, and LC-MS analysis revealed unmetabolized prodrug in the systemic circulation. The medoxomil ester prodrug 10 showed complete conversion and sufficient bioavailability of 9 to advance into further preclinical testing for treatment of heart failure.
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PMID:Synthesis and pharmacological properties of a new hydrophilic and orally bioavailable 5-HT4 antagonist. 2371 70

Recent advances in brain science have shown that the brain function encoding emotion depends on interoceptive signals such as visceral pain. Visceral pain arose early in our evolutionary history. Bottom-up processing from gut-to-brain and top-down autonomic/neuroendocrine mechanisms in brain-to-gut signaling constitute a circuit. Brain imaging techniques have enabled us to depict the visceral pain pathway as well as the related emotional circuit. Irritable bowel syndrome (IBS) is characterized by chronic recurrent abdominal pain or abdominal discomfort associated with bowel dysfunction. It is also thought to be a disorder of the brain-gut link associated with an exaggerated response to stress. Corticotropin-releasing hormone (CRH), a major mediator of the stress response in the brain-gut axis, is an obvious candidate in the pathophysiology of IBS. Indeed, administration of CRH has been shown to aggravate the visceral sensorimotor response in IBS patients, and the administration of peptidergic CRH antagonists seems to alleviate IBS pathophysiology. Serotonin (5-HT) is another likely candidate associated with brain-gut function in IBS, as 5-HT3 antagonists, 5-HT4 agonists, and antidepressants were demonstrated to regulate 5-HT neurotransmission in IBS patients. Autonomic nervous system function, the neuroimmune axis, and the brain-gut-microbiota axis show specific profiles in IBS patients. Further studies on stress and visceral pain neuropathways in IBS patients are warranted.
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PMID:Stress and visceral pain: focusing on irritable bowel syndrome. 2402 63

Serotonergic mechanisms are involved in many, if not all digestive functions of the gastrointestinal tract. A special role is played by serotoninergic structures in the neuronal control of motor activity. The study of these structures is of particular interest due to the widespread occurrence of irritable bowel syndrome, covering up to 20% of the adult population, which makes the research in this area up to date and in demand. Acute experiments were performed on 102 Wistar rats in 6 series. Experiments were carried out under general anesthesia (Nembutal, 60 mg/kg) and mechanical lung ventilation. Motor responses of the stomach, duodenum and ascending colon were studied to i.a. Serotonin adipate infusion (1 mg/kg) during joint blockade of sympathetic and parasympathetic chains of ANS, as well as on the background of the blockade of various 5-HT-receptors. Infusions of 5-HT-blockers reduce the magnitude of motor responses in stomach, duodenum and colon in varying degrees. Based on these data found 5-HT(1b)-receptors are mainly located in enteric neurons. The distribution of 5-HT(2b-4)-receptor is heterogeneous: 5-HT(2b)-receptors are located in enteric neurons of the stomach and intestinal myocytes; 5-HT3-receptors localized in the ganglia supplying the stomach and colon and 5-HT4-receptors are mainly located in the smooth muscle of the stomach, duodenal and ascendent colon enteric neurons.
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PMID:[The significance of different 5-HT-receptors in regulation of gastrointestinal motility]. 2553 90

The importance of prokinetics (drugs stimulating motor function of the gastrointestinal tract) arises from the high prevalence of gastroenterological pathology associated with primary or secondary disturbances of this function in esophagus, stomach, and intestines. The main groups of prokinetics are beta-blockers of dopamine receptors, inhibitors of acetylcholine esterase (or their combination with dopamine receptor blockers), 5-HT4-receptor agonists. They find wide application for the treatment of gastroesophgeal reflux disease, functional dyspepsia and constipation, obstipational form of irritable bowel syndrome, and other conditions accompanied by motor function disorders of the gastrointestinal tract.
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PMID:[MODERN PROKINETICS AND THEIR ROLE IN THE TREATMENT OF GASTROENTEROLOGICAL PATHOLOGY]. 2752 21


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