tegaserod and cilansetron

Irritable bowel syndrome (IBS) is a chronic functional disorder. 5-Hydroxytryptamine (5-HT) is a key modulator of gastrointestinal sensorimotor function. Many patients have IBS that can be difficult to treat, which has led to the development of newer agents, such as 5-HT(3) antagonists and 5-HT(4) agonists. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to estimate the efficacy of all available 5-HT agents in IBS.. MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched (up to June 2008). Trials recruiting adults with IBS in primary, secondary, or tertiary care comparing 5-HT(3) antagonists or 5-HT(4) agonists with placebo were eligible. Dichotomous symptom data were pooled to obtain a relative risk (RR) of remaining symptomatic after therapy, with a 95% confidence interval (CI). The number needed to treat (NNT) was calculated from the reciprocal of the risk difference.. The strategic search identified 1,593 citations. A total of 29 RCTs were eligible for inclusion; placebo was compared with 5-HT(3) antagonists in 11 RCTs, with tegaserod in 11, and with mixed 5-HT(3) antagonists/5-HT(4) agonists in 7. The study quality was generally high. The RR of IBS symptoms persisting with 5-HT(3) antagonists vs. placebo was 0.78 (95% CI: 0.71-0.86), with a similar benefit for both alosetron and cilansetron. Tegaserod was also superior to placebo (RR=0.85; 95% CI: 0.80-0.90). Renzapride and cisapride had no benefit in IBS.. Alosetron, cilansetron, and tegaserod are all effective in the treatment of IBS. Serious adverse events were rare in the eligible RCTs included in this systematic review.

Topics: Adult; Age Factors; Aged; Carbazoles; Carbolines; Dose-Response Relationship, Drug; Drug Administration Schedule; Education, Medical, Continuing; Female; Humans; Indoles; Irritable Bowel Syndrome; Male; Middle Aged; Patient Satisfaction; Pyridines; Quality of Life; Randomized Controlled Trials as Topic; Risk Assessment; Serotonin Antagonists; Severity of Illness Index; Sex Factors; Treatment Outcome

Topics: Antidepressive Agents; Benzofurans; Carbazoles; Carbolines; Colonic Diseases, Functional; Gastrointestinal Agents; Humans; Indoles; Physical Examination; Pyridines

As the use of the 5-HT(3) receptor antagonist alosetron (GlaxoSmithKline) and the 5-HT(4) receptor agonist tegaserod (Novartis) in patients with irritable bowel syndrome has been associated with cases of ischaemic colitis, the effects of alosetron, cilansetron (Solvay) and tegaserod on the rat splanchnic circulation were evaluated.. Phenobarbital-anaesthetised rats were instrumented to record blood flow in the superior mesenteric artery and transverse colon and to calculate mesenteric and colonic vascular conductance.. Intravenous alosetron (0.03-0.3 mg.kg(-1)) did not alter blood pressure or heart rate but reduced mesenteric blood flow and vascular conductance by 15-20%. This activity profile was also seen after intraduodenal alosetron and shared by the 5-HT(3) receptor antagonist cilansetron. In contrast, blood flow, vascular conductance and intraluminal pressure in the colon were not modified by alosetron and cilansetron. Intravenous or intraduodenal tegaserod (0.3-1.0 mg.kg(-1)) had no inhibitory effect on mesenteric and colonic blood flow. Peroral treatment of rats with alosetron or tegaserod for 7 days did not modify mesenteric haemodynamics at baseline and after blockade of nitric oxide synthesis. Mild inflammation induced by dextran sulphate sodium failed to provoke a vasoconstrictor effect of cilansetron in the colon.. Alosetron and cilansetron, not tegaserod, caused a small and transient constriction of the rat mesenteric vascular bed, whereas blood flow in the colon remained unaltered. The relevance of these findings to the treatment-associated occurrence of ischaemic colitis in patients with irritable bowel syndrome remains open.

Topics: Adrenergic alpha-Agonists; Animals; Blood Pressure; Carbazoles; Carbolines; Clonidine; Colitis; Colon; Fasting; Female; Heart Rate; Indoles; Mesenteric Artery, Superior; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Pyridines; Rats; Rats, Sprague-Dawley; Regional Blood Flow; Serotonin 5-HT3 Receptor Antagonists; Serotonin 5-HT4 Receptor Antagonists; Splanchnic Circulation; Vasoconstrictor Agents; Vasodilator Agents