A Risk-Benefit Assessment of Cisapride in the Treatment of Gastrointestinal Disorders

Abstract

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)

Effects of gastroprokinetic agents on gastroparesis in streptozotocin-induced diabetic rats

“…Ramosetron and the substituted benzamides cisapride and zacopride partially reversed the gastroparesis in vagotomized rats. It was reported that cisapride produced a gastroprokinetic response in both healthy men and gastroparesis patients (Wiseman and Faulds 1994;Duan et al 1995;Horowitz and Fraser 1995;Tack et al 1995). In contrast, the gastroprokinetic effects of the selective 5-HT 3 receptor antagonists ondansetron and tropisetron were weak in humans, in contrast to rats (Akkermans et al 1988;Gore et al 1990;Stacher et al 1990;Talley 1991).…”

Assessment of meal induced gastric accommodation by a satiety drinking test in health and in severe functional dyspepsia

“…5 31-33 Sumatriptan slows gastric emptying whereas cisapride and erythromycin are both gastroprokinetic drugs. [34][35][36] As the end point of the satiety test was enhanced by sumatriptan and cisapride and decreased by erythromycin, the influence of these agents matches their influence on gastric accommodation, and not their influence on gastric emptying rate. The satiety drinking test therefore offers the potential to screen for drugs that might improve impaired accommodation in a non-invasive way.…”

Effects of a serotonin 5-HT4 receptor antagonist SB-207266 on gastrointestinal motor and sensory function in humans

“…While 5-HT 4 receptor agonists are known to enhance gut contractility in humans,26 the contribution of 5-HT 4 receptors to regulating gastrointestinal motor and sensory function can only be assessed with a 5-HT 4 antagonist. In this respect, therefore, this is the first study to assess the contribution of 5-HT 4 receptors on gastrointestinal motor and sensory function in vivo in normal humans.…”

“…These are notable for interspecies and interorgan variability,5 dependence on 5-HT induced sensitisation,3 4 and/or coexistent 5-HT 3 receptor antagonism 1236 37 Cisapride, a 5-HT 4 receptor agonist with weak 5-HT 3 antagonist effects, increases upper gut contractility in humans and colonic contractility in the guinea pig, mainly by stimulating 5-HT 4 receptors on enteric neurones, leading to enhanced release of acetylcholine 26. In contrast, 5-HT acts on 5-HT 4 receptors in colonic smooth muscle to reduce the amplitude and frequency of contractions, causing relaxation 5-7.…”