[New therapeutical approaches for treatment of irritable bowel syndrome]. 2010

Fritzi Siegert, and Karen Nieber
Institut für Pharmazie, Lehrstuhl Pharmakologie für Naturwissenschaftler, Leipzig.

Irritable bowel syndrome is a common functional disorder of the gut. The cause is not known. Symptoms can be quite variable and include abdominal pain, bloating, and sometimes bouts of diarrhea and/or constipation. It causes a great deal of discomfort and distress, but it does not permanently harm the intestine and does not lead to a serious disease, such as cancer. There are numerous treatment options in functional gastrointestinal disorders acting peripherally by influencing motility and visceral sensitivity. However, older 5-HT4 receptor agonists had limited clinical success because they were associated with changes in the cardiac function. New generation 5-HT4 receptor agonists, 5-HT, antagonists or partial antagonists are promising approaches to treat gastrointestinal dysmotility, particularly colonic diseases. A further new approach is the activation of chloride cannels within the gastrointestinal wall by the prostaglandin E metabolite lubiprostone. In patients with chronic constipation, lubiprostone produced a bowel movement, with sustained improvement in frequency as well as other constipation symptoms. Ongoing clinical trials suggest that linaclotide, a first-in-class, 14-amino acid peptide guanylate cyclase C (GC-C) receptor agonist and intestinal secretagogue is also an effective treatment for chronic constipation. The pharmacological profile suggests that orally administered linaclotide may be capable of improving the abdominal symptoms and bowel habits of patients suffering from of constipation-predominant irritable bowel syndrome and chronic constipation. Data are emerging, but the efficacy and safety profile of these agents in the treatment irritable bowel disease appears encouraging. Further randomized controlled trials are warranted.

UI MeSH Term Description Entries
D004789 Enzyme Activation Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme. Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D006162 Guanylate Cyclase An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. Guanyl Cyclase,Deoxyguanylate Cyclase,Guanylyl Cyclase,Inosinate Cyclase,Cyclase, Deoxyguanylate,Cyclase, Guanyl,Cyclase, Guanylate,Cyclase, Guanylyl,Cyclase, Inosinate
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012702 Serotonin Antagonists Drugs that bind to but do not activate serotonin receptors, thereby blocking the actions of serotonin or SEROTONIN RECEPTOR AGONISTS. 5-HT Antagonist,5-HT Antagonists,5-Hydroxytryptamine Antagonist,5-Hydroxytryptamine Antagonists,Antiserotonergic Agent,Antiserotonergic Agents,Serotonin Antagonist,Serotonin Blockader,Serotonin Blockaders,Serotonin Receptor Antagonist,Serotonin Receptor Blocker,Antagonists, 5-HT,Antagonists, 5-Hydroxytryptamine,Antagonists, Serotonin,Serotonin Receptor Antagonists,Serotonin Receptor Blockers,5 HT Antagonist,5 HT Antagonists,5 Hydroxytryptamine Antagonist,5 Hydroxytryptamine Antagonists,Agent, Antiserotonergic,Agents, Antiserotonergic,Antagonist, 5-HT,Antagonist, 5-Hydroxytryptamine,Antagonist, Serotonin,Antagonist, Serotonin Receptor,Antagonists, 5 HT,Antagonists, 5 Hydroxytryptamine,Antagonists, Serotonin Receptor,Blockader, Serotonin,Blockaders, Serotonin,Blocker, Serotonin Receptor,Blockers, Serotonin Receptor,Receptor Antagonist, Serotonin,Receptor Antagonists, Serotonin,Receptor Blocker, Serotonin,Receptor Blockers, Serotonin
D043183 Irritable Bowel Syndrome A disorder with chronic or recurrent colonic symptoms without a clearcut etiology. This condition is characterized by chronic or recurrent ABDOMINAL PAIN, bloating, MUCUS in FECES, and an erratic disturbance of DEFECATION. Colitis, Mucous,Colon, Irritable,Colitides, Mucous,Irritable Bowel Syndromes,Irritable Colon,Mucous Colitides,Mucous Colitis,Syndrome, Irritable Bowel,Syndromes, Irritable Bowel
D018118 Chloride Channels Cell membrane glycoproteins that form channels to selectively pass chloride ions. Nonselective blockers include FENAMATES; ETHACRYNIC ACID; and TAMOXIFEN. CaCC,Calcium-Activated Chloride Channel,Chloride Ion Channel,Chlorine Channel,Ion Channels, Chloride,CaCCs,Calcium-Activated Chloride Channels,Chloride Channel,Chloride Ion Channels,Chlorine Channels,Ion Channel, Chloride,Calcium Activated Chloride Channel,Calcium Activated Chloride Channels,Channel, Calcium-Activated Chloride,Channel, Chloride,Channel, Chloride Ion,Channel, Chlorine,Channels, Calcium-Activated Chloride,Channels, Chloride,Channels, Chloride Ion,Channels, Chlorine,Chloride Channel, Calcium-Activated,Chloride Channels, Calcium-Activated

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