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 effects of prokinetic treatment with cisapride in patients with constipation-predominant irritable bowel syndrome (IBS) were evaluated in a randomized, double-blind, placebo-controlled study. Sixty-nine IBS patients were assigned to a 12-week treatment with either 5 mg cisapride or placebo t.i.d.; this dosage could be changed if necessary. The mean weekly number of days on which a stool was passed in the cisapride and placebo group increased to 5.3 and 4.4 (p less than 0.05) during weeks 8-12 of treatment, and the number of days with stools of normal consistency increased to 3.5 and 1.9 (p less than 0.05), respectively. At week 12, the reduction in severity and frequency scores for abdominal pain was significantly greater (p less than or equal to 0.05) in the cisapride group (60 and 61%) than in the placebo group (40 and 32%), as it was for abdominal distension (p less than 0.05). Cisapride tended to be better than placebo in diminishing flatulence. In 71% versus 39% of the patients the overall rating for the response to treatment was good or excellent at week 12. Cisapride was well tolerated. These results suggest that the drug will be useful for the management of constipation-predominant IBS.
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PMID:"Prokinetic" treatment of constipation-predominant irritable bowel syndrome: a placebo-controlled study of cisapride. 200 45

Diarrhea of colonic origin is fairly common in irritable colon and after long term abuse of laxatives. This form of diarrhea causes difficulties not only in diagnosis but also in treatment. Irritable colon is a functional disorder sometimes involving other segments of the bowel. The term "irritable bowel disease" is thus more appropriate. Extraintestinal symptoms are in addition quite common. Although the diagnosis can be established with great reliability using an index we consider some laboratory tests, recto-sigmoidoscopy and abdominal sonography essential to rule out organic lesions. Therapy comprises (small) psychotherapy, dietary measures and eventually transient medication. Symptoms usually persist but tolerance of the disorder should be improved. Laxative-induced colonic dysfunction results usually from false assumptions about normal defecation. Loss of water and potassium deteriorates the symptomatology leading to a vicious circle. Alterations of neurons in the enteric nervous system of the colon can be the cause but eventually the consequence of chronic intake of laxatives. Hidden abuse of laxatives can cause great diagnostic difficulties. The therapy of choice is weaning which usually is only possible gradually. Cisapride can be a useful adjuvant.
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PMID:[Irritable colon and colonic disease due to laxatives]. 219 2

Cisapride is an orally administered prokinetic agent which facilitates or restores motility throughout the length of the gastrointestinal tract. It is a substituted piperidinyl benzamide, chemically related to metoclopramide, but unlike metoclopramide, cisapride is largely devoid of central depressant or antidopaminergic effects. In placebo-controlled trials, cisapride improved healing rates and symptoms in both adults and children with reflux oesophagitis. Maintenance therapy with cisapride at half the healing dose is effective in reducing the incidence of relapse. Symptoms are also alleviated in patients with functional dyspepsia, and gastric emptying and symptoms are improved in most patients with gastroparesis, an effect which is sustained during long term administration. However, the efficacy of cisapride in end-stage gastroparesis remains less clear. Cisapride increases stool frequency in patients with chronic constipation, and limited data suggest that the drug may also be beneficial in treating chronic intestinal pseudo-obstruction and irritable bowel syndrome. Cisapride demonstrated efficacy comparable with or superior to that of metoclopramide, and was at least as effective as cimetidine and ranitidine in patients with reflux disease. In patients with functional dyspepsia, cisapride has shown at least equal efficacy to domperidone, metoclopramide and ranitidine, and superior efficacy to cimetidine in the small comparative trials conducted to date. Adverse effects in patients receiving cisapride are generally transient and mild, with abdominal cramping, borborygmi, diarrhoea or loose stools most frequently reported. Central nervous system adverse effects are rare. Thus, with its favourable tolerability profile and demonstrated efficacy in a variety of gastrointestinal motility disorders, the position of cisapride as a valuable agent in the management of patients with gastrointestinal motility disorders is strengthening. However, larger well-controlled comparative trials of the drug with other agents are necessary before the relative position of cisapride in therapy can be categorically defined.
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PMID:Cisapride. An updated review of its pharmacology and therapeutic efficacy as a prokinetic agent in gastrointestinal motility disorders. 751 Jun 17

Prokinetic agents are currently being investigated as potential therapies for motility disorders of the lower gastrointestinal tract. Cholinergic agonists such as bethanechol are known to improve postoperative ileus but are limited because of side effects. Dopamine antagonists such as domperidone appear to have maximal prokinetic effect in the proximal gastrointestinal tract and are effective for such conditions as gastroparesis and gastroesophageal reflux, but they appear to have little physiologic effect in the colon or in colonic motility disorders. Naloxone, an opioid antagonist, appears to hold promise in patients with irritable bowel syndrome, small intestinal pseudo-obstruction, and constipation. Erythromycin exerts its prokinetic effect by acting as a motilin agonist; it has been used in the treatment of diabetic gastroparesis and appears to improve symptoms of colonic pseudo-obstruction and postoperative ileus. Metoclopramide, a combined cholinergic agonist and dopamine antagonist, is currently used exclusively for proximal motility dysfunction. Cisapride appears to hold the most promise for patients with colonic motility disorders. In patients with postoperative ileus, cisapride is associated with an increased return of bowel function compared with placebo. In patients with chronic constipation, cisapride increases stool frequency and decreases laxative abuse in both adults and children. Hopefully, as an understanding of gastrointestinal motility increases, effective prokinetic agents will be developed that will improve symptoms of patients with large bowel motility disorders and may also help to predict those patients who benefit from surgical management for constipation.
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PMID:Prokinetic agents for lower gastrointestinal motility disorders. 813 79

Cisapride is a substituted benzamide compound that stimulates motor activity in all segments of the gastrointestinal tract by enhancing the release of acetylcholine from the enteric nervous system. Cisapride is administered orally in the treatment of gastro-oesophageal reflux disease, functional dyspepsia, gastroparesis, chronic intestinal pseudo-obstruction syndromes and chronic constipation. In gastro-oesophageal reflux disease in both adults and children, cisapride provides symptomatic improvement and mucosal healing. Long term treatment with cisapride is effective in the prevention of relapse of oesophagitis. Cisapride improves gastric emptying rates and improves symptoms in patients with gastroparesis of various origins. Unlike domperidone and metoclopramide, long term administration of cisapride seems to result in persistently enhanced gastric emptying. Cisapride is also effective in improving symptoms in patients with functional dyspepsia. In comparative studies in patients with functional dyspepsia, cisapride was at least as effective as metoclopramide, domperidone, clebopride, ranitidine and cimetidine. Cisapride increases stool frequency and reduces laxative consumption in patients with idiopathic constipation. Severe cases of slow transit constipation seem refractory to cisapride. Clinical studies also indicate that cisapride might be effective in the treatment of chronic intestinal pseudo-obstruction, postoperative ileus, peptic ulcer and irritable bowel syndrome. Further clinical studies are warranted to define the role of cisapride in these conditions. The dosage of cisapride ranges from 5mg 3 times daily to 20mg twice daily. Cisapride is generally well tolerated, both during short and long term treatment. In children, cisapride is also well tolerated in doses of 0.2 to 0.3 mg/kg, 3 to 4 times daily.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A risk-benefit assessment of cisapride in the treatment of gastrointestinal disorders. 852 13

Some drugs acting on 5-hydroxytryptamine receptors inhibit the rapid component of delayed rectifying potassium currents (I(Kr)) in cardiac muscle cells. This is associated with lengthening of the QT interval in the cardiac cycle and can lead to fatal arrhythmias. We investigated whether alosetron, a novel 5HT3 antagonist proposed for treatment of irritable bowel syndrome (IBS), blocks I(Kr) in guinea pig cardiac myocytes. I(Kr) was isolated under whole-cell voltage clamp, and was identified by its sensitivity to the selective I(Kr) antagonist E4031. Cisapride (10(-6) M) inhibited the E4031-sensitive current while alosetron (10(-10)-10(-6) M) had no effect on I(Kr). We also found that alosetron did not inhibit I(Ks). Therefore, use of alosetron for treatment of IBS should not be confounded by long QT syndrome.
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PMID:Alosetron and the rapid component of delayed rectifying potassium current in cardiac cells. 1126 71

Drug development for functional gastrointestinal disorders is complex. These conditions involve central and peripheral physiological changes, together with psychological factors. Methodological problems have included a poor appreciation of the physiological and psychological correlates of patients' symptoms, a lack of animal models of proven relevance, and safety issues. Government, patient pressure groups and the Internet can also influence a drug's success. Most recent interest has focused on the serotonin (5-HT) modifying drugs. Cisapride has been withdrawn in some countries because of concerns related to QT prolongation and cardiac arrhythmias. The 5-HT3 antagonists, developed to modify visceral sensation, have caused constipation; alosetron, also withdrawn, caused ischaemic colitis. The 5-HT4 agonists induce peristalsis; tegaserod and prucalopride, both delayed in their development due to issues of safety and efficacy, benefit patients with 'constipation-predominant' irritable bowel syndrome or idiopathic constipation. 5-HT1 agonists improve impaired gastric accommodation and symptoms in patients with functional dyspepsia. Antidepressants also affect serotonin metabolism. Previous examples of success in this area involved drugs targeted at peripheral receptors mediating motor function or secretion. Modification of sensory function is a much more challenging objective. The experience with serotonin modifying drugs has been mixed, and some important lessons are there to be learnt.
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PMID:Review article: the complexity of drug development for irritable bowel syndrome. 1187 86

The aim of this study was to assess the cardiovascular effect of MA-2029, a selective motilin receptor antagonist highly expected for the treatment of irritable bowel syndrome (IBS). MA-2029 inhibited the human ether-a-go-go-related gene (hERG) current at 100 microg/ml, but shortened action potential duration (APD) in isolated guinea pig papillary muscles at 10 and 100 microg/ml and the corrected QT (QTc) interval after oral administration of 30 and 300 mg/kg in conscious telemetered dogs. The discrepancy was probably caused by blockade of the Ca(2+) channel because MA-2029 inhibited the Ca(2+) current in isolated guinea pig myocytes. MA-2029 at 100 microg/ml also decreased the maximum rising velocity and action potential amplitude in the action potential study, indicating that MA-2029 has Na(+) channel blocking potential. In the cardiovascular study, MA-2029 at 30 mg/kg induced slight cardiovascular changes such as hypotension, QTc shortening, and PR prolongation possibly caused by Ca(2+) channel blockade. The plasma concentration at 4 hr after 30 mg/kg administration was 2.10 microg/ml, 200-fold higher than the effective concentration of MA-2029 as a motilin receptor antagonist. These results suggest that MA-2029 has sufficient cardiovascular safety although it inhibits multiple ion channels at supra-effective concentrations. On the other hand, cisapride, an effective IBS drug, showed clear hERG inhibition and APD prolongation at 100 ng/ml. Cisapride exhibited a narrow safety margin because it caused QT prolongation potential even at the therapeutic concentration. In conclusion, MA-2029 is a novel drug highly expected for the treatment of IBS with lower cardiovascular risk than cisapride.
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PMID:Cardiovascular safety profile of MA-2029, a novel motilin receptor antagonist. 1904 84