Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: CAS:81098-60-4 (Cisapride)
 330 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of an erythromycin derivative, EM-523, on gastrointestinal motility was investigated in conscious dogs and compared with that of motilin cisapride, trimebutine and metoclopramide. In the fasting state, EM-523 given i.v. or i.d. at 3 micrograms/kg or more induced contractions in the stomach that migrated along the small intestine. The pattern of the contractions was very similar to that induced by motilin. In the digestive state, EM-523 increased the amplitude of gastric contractions. Cisapride and metoclopramide increased gastrointestinal motility both in the fasting and digestive states; however, their contractile pattern was different from that of EM-523. Trimebutine did not induce gastric motility in the fasting state but rather decreased gastric motility in the digestive state. The contractions induced by EM-523 and motilin were inhibited by atropine but were not affected by naloxone, suggesting that the cholinergic pathway is important in the exertion of their action. These results indicate that EM-523 mimics motilin in stimulating gastrointestinal motility and that this agent may be useful treat gastrointestinal disorders such as gastric stasis, gastroesophageal reflux, and postoperative ileus, and so forth.
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PMID:An erythromycin derivative, EM-523, induces motilin-like gastrointestinal motility in dogs. 281 Jan 20

The authors evaluated the in vivo effects of the new drug Cisapride on gastrointestinal hormone release in the mini-pig. Cisapride has been reported to stimulate and coordinate peristalsis of the GI tract. Selective endoluminal perfusion with Cisapride solution of the isolated but not denervated gastric antrum, duodenum and distal ileum demonstrated a significant increase of gastrin levels following perfusion of the gastric antrum and a decrease in vasoactive intestinal peptide following perfusion of the duodenum, only at very high doses.
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PMID:Digestive tract endoluminal perfusion of cisapride (R 51619) and effects on gastrointestinal hormone levels in anaesthetized pigs. 287 79

The excretion and biotransformation of cisapride, a novel gastrokinetic drug, were studied after single (10, 40, and 160 mg/kg) and repeated (10 mg/kg/day) po administration to rats, using three different radiolabels. In fasted rats, cisapride was absorbed almost completely, except for the 160 mg/kg dose. Cisapride was metabolized extensively to at least 30 metabolites. The excretion of the metabolites amounted to more than 80% of the dose at 24 hr and was almost complete at 96 hr after dosing. In bile duct-cannulated rats, 60% was excreted in the bile within 24 hr, 45% of which underwent enterohepatic circulation. The main urinary metabolites, 4-fluorophenyl sulfate and norcisapride, primarily resulted from the N-dealkylation at the piperidine. Another major metabolic pathway was aromatic hydroxylation, occurring on either the 4-fluorophenoxy or the benzamide rings. The resulting phenolic metabolites were eliminated as conjugates in the bile; a large portion of them were subjected to a rapid enterohepatic circulation before their final excretion in the feces. Minor metabolic pathways included piperidine oxidation, O-dealkylation, O-demethylation of the methoxy substituent at the benzamide, and amine glucuronidation. Only minor quantitative dose- and sex-dependent differences could be observed for the mass balance of the metabolites. Upon repeated po dosing, steady state excretion rates were already attained after two to three doses, and excretion and metabolite patterns were very similar to those after single dose administration.
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PMID:Excretion and biotransformation of cisapride in rats after oral administration. 290 Jul 33

The aim of the present study was to investigate the effect of cisapride on the myoelectric activity of the small intestine in the rat. Intestinal myoelectric activity of fasted conscious rats was monitored by three bipolar electrodes chronically implanted at 5, 15 and 25 cm distal to the pylorus and connected to an EEG amplifier. In the basal state, regularly occurring migrating myoelectric complexes (MMCs) and clustered spikes were registered. Cisapride at doses of 0.5-4.0 mg-1 i.v. did not affect the MMCs, but at 8 mg kg-1 i.v. the regular MMCs were replaced by irregular spiking activity (p less than 0.05). Concomitantly cisapride increased the occurrence of clustered spikes and abbreviated the interval between them in a dose-dependent manner (p less than 0.05), without affecting their duration. Hexamethonium at a dose of 10 mg kg-1 i.v. abolished the MMCs as well as the stimulatory effect of ciSapride (4 mg kg-1). Atropine at a dose of 1 mg kg-1 i.v. did not affect the MMCs but blocked the stimulatory effect of cisapride (4 mg kg-1). It is concluded that cisapride induces clustered spikes and irregular spiking. These effects require intact cholinergic pathways, involving both muscarinic and nicotinic receptor mechanisms.
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PMID:Cisapride induces clustered spikes and irregular spiking of the small intestine of the rat. 290 90

A prospective double-blind cross-over trial of oral cisapride 10 mg and placebo was performed to determine the effects of cisapride on the transit of colonic contents in normal humans. Six male volunteers were studied twice using colonic transit scintigraphy. After passing a tube to the caecum, 50 mu Ci of 111Indium diethylene triamine pentaacetic acid were instilled into the bowel lumen. The movement of radiolabelled material was followed using a gamma camera interfaced to a digital computer. Cisapride decreased the half-emptying of the caecum and ascending colon from 1.68 +/- 0.4 hours to 0.72 +/- 0.15 hours (P less than 0.05). The total colon half-emptying time was reduced from 38.5 +/- 7.2 hours to 11.1 +/- 2.9 hours on cisapride (P less than 0.05). Cisapride accelerated transit through the transverse colon, but not the descending colon. The progression of the geometric centre was faster during cisapride administration than with placebo (P less than 0.05). The number of bowel movements 48-hours-1 increased after cisapride from 2.5 +/- 0.8 to 5.0 +/- 0.4 (P less than 0.05). This study demonstrates that cisapride has a marked prokinetic effect on colonic transit in normal subjects. Cisapride may be a useful agent in the treatment of constipation.
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PMID:The effect of oral cisapride on colonic transit. 297 74

In the guinea-pig ileum, pretreatment with 5-hydroxytryptamine (5-HT) (5 microM) for 4-5 min inhibited both 5-HT- and gamma-aminobutyric acid (GABA)-induced cholinergic contractions without consistently altering those induced by electrical field stimulation. Cisapride (1 micron) antagonized 5-HT-induced cholinergic contractions but left those induced by GABA or twitch responses unchanged. These results indicate that the 5-HT action in inhibiting GABA-induced cholinergic responses may arise at the interneuronal level, thus suggesting that GABA may also indirectly activate cholinergic terminal neurons. These findings rule out the possibility of 5-HT acting as an intermediate transmitter in this type of response.
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PMID:A re-appraisal of the mode of action of 5-HT in inhibiting GABA-induced cholinergic contractions in the guinea-pig ileum. 301 31

Cisapride, a substituted piperidinyl benzamide chemically related to metoclopramide, is an orally administered prokinetic agent which facilitates or restores motility throughout the length of the gastrointestinal tract. Its novel mechanism of action is thought to involve enhancement of acetylcholine release in the myenteric plexus of the gut. Because of its specificity cisapride is devoid of central depressant or antidopaminergic effects; side effects such as diarrhoea or loose stools, which occur infrequently, are related to its primary pharmacological action. Evidence exists from comparisons with placebo in initial trials to establish the efficacy of cisapride in improving healing rates and symptoms in patients with reflux oesophagitis, in alleviating symptoms in patients with non-ulcer dyspepsia, and in accelerating gastric emptying in gastroparesis. There are less conclusive data regarding the efficacy of cisapride in relieving symptoms in patients with gastroparesis, although preliminary results support a role for cisapride in certain groups such as diabetics. Limited data suggest that patients with chronic constipation due to underlying motility disorders may benefit from cisapride. Unfortunately, there is a paucity of trials comparing the efficacy of cisapride with other therapeutic agents. Thus, the relative position of cisapride in therapy cannot be defined at present. Should future results support preliminary evidence of comparable efficacy to metoclopramide, domperidone and ranitidine (in oesophagitis), cisapride with its favourable tolerability profile should claim a prominent position in the therapy of patients with a variety of gastrointestinal motility disorders.
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PMID:Cisapride. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use as a prokinetic agent in gastrointestinal motility disorders. 306 57

In a 6 to 12-week double-blind trial, the effect of cisapride (10 mg q.i.d.) was compared with that of placebo in 63 patients with esophagitis confirmed by endoscopy and/or biopsy. In only one patient (3%) in the cisapride group but in 43% of the placebo patients (p = 0.001), symptoms had not improved after 6 weeks. Forty patients continued treatment until week 12. At that time, control endoscopy showed a significantly (p = 0.005) higher rate of healing (no erosions, ulcers, or bleeding mucosa) in the cisapride patients (63%) than in the placebo patients (12%). At week 12, only three of the 21 cisapride patients still had moderate reflux symptoms, whereas eight of the 19 placebo patients had moderate or severe symptoms (p less than 0.05). Cisapride patients also took significantly (p less than 0.001) less antacids during the trial. These results show that cisapride, 10 mg q.i.d., heals esophagitis lesions and greatly reduces associated symptoms. The treatment was well tolerated.
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PMID:Cisapride versus placebo in reflux esophagitis. A multicenter double-blind trial. 306

1. The effects of metoclopramide or cisapride on morphine-induced delay in gastric emptying in patients before surgery were compared. 2. Forty patients were allocated randomly to receive one of four premedications i.m.: placebo only, morphine 10 mg alone, morphine 10 mg with metoclopramide 10 mg and morphine 10 mg with cisapride 10 mg. Gastric emptying after each premedication was assessed indirectly from the rate of absorption of oral paracetamol. 3. Cisapride 10 mg reversed the delay in gastric emptying due to morphine. Its effects were significantly greater than those of metoclopramide 10 mg.
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PMID:Comparison of the effect of cisapride and metoclopramide on morphine-induced delay in gastric emptying. 307 16

The effects of cisapride on upper gut motility were studied in seven healthy volunteers by means of a novel intraluminal electromyographic technique in a placebo-controlled study. In the interdigestive state, cisapride (10 mg intravenous bolus injection) markedly increased the number of spike bursts. The most obvious effect was observed during the first 5-min period when a nonmigrating phase-3-like activity (stationary phase 3) occurred, which lasted for 2.6 +/- 0.4 min. This initial pattern was followed by an intense phase 2 activity, characterized by a 10-fold increase in the number of groups of repetitive spike bursts and a sixfold increase in the number of ultrarapid single propagated spike bursts (ultrarapid peristaltic rushes). Cisapride induces in the human upper gut a remarkable pattern of aborally propagated (peristaltic) contractions, which are very likely responsible for the active propulsion of intestinal contents in the interdigestive state.
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PMID:Cisapride stimulates propulsive motility patterns in human jejunum. 319 80


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