Delayed gastric emptying after Billroth I pylorus-preserving pancreatoduodenectomy: effect of postoperative time and cisapride.
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OBJECTIVE: To study the recovery course of gastric emptying after Billroth I pylorus-preserving pancreatoduodenectomy (PPPD) and therapeutic effects of cisapride. METHODS: To examine gastric emptying, acetaminophen was given, admixed in a pasty liquid meal, to 16 patients undergoing PPPD before surgery and at 1, 3, 6, 9, and 12 months after surgery. Cisapride was given orally to 10 patients before they received the acetaminophen regimen. Electrogastrography was performed at 2 weeks to 1 month after surgery in eight patients and at 6 to 12 months after surgery in seven patients. RESULTS: Gastric emptying was delayed but returned to the preoperative level by 6 months after surgery. Pretreatment with cisapride accelerated gastric emptying during months 1 to 6 but not during months 6 to 12 after surgery. Electrogastrography frequently showed tachygastria 2 weeks to 1 month after surgery, but seldom 6 to 12 months after surgery. CONCLUSIONS: After Billroth I PPPD, gastric emptying is delayed but recovers by 6 months after surgery. Tachygastria may play a part in the pathogenesis of delayed gastric emptying, but it can be treated with cisapride. (+info)
Intestinal prokinesia by two esters of 4-amino-5-chloro-2- methoxybenzoic acid: involvement of 5-hydroxytryptamine-4 receptors and dissociation from cardiac effects in vivo.
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In five fasting, conscious dogs, we compared the prokinetic action of two selective 5-hydroxytryptamine-4 (5-HT4) receptor agonists with low affinity for 5-HT3 receptors ML10302 (2-piperidinoethyl 4-amino-5-chloro-2-methoxybenzoate) and SR59768 (2-[(3S)-3-hydroxypiperidino]ethyl 4-amino-5-chloro-2-methoxybenzoate) in the duodenum and jejunum, using cisapride as a reference compound. Heart rate and rate-corrected QT (QTc) also were monitored to assess whether or not the cardiac effects of cisapride are shared by other 5-HT4 receptor agonists. Both ML10302 and SR59768 dose-dependently stimulated spike activity in the duodenum with similar potencies (dose range, 3-300 nmol/kg i.v.; ED50 values: 24 and 23 nmol/kg i.v., respectively), mimicking the effect of cisapride (30-3000 nmol/kg i.v.). The maximal effect was achieved with the dose of 100 nmol/kg i.v. for both compounds. Similar findings were obtained in the jejunum. Atropine and GR125487 (1-[2-[(methylsulfonyl)amino]ethyl]-4-piperidinyl-methyl 5-fluoro-2-methoxy-1H-indole-3-carboxylate, selective 5-HT4 receptor antagonist), at doses having no effect per se, antagonized intestinal prokinesia by maximal doses of ML10302 and SR59768. Neither ML10302 nor SR59768 had any effect on heart rate or QTc at any of the doses tested, whereas cisapride, at the highest dose (3000 nmol/kg), induced tachycardia and lengthened the QTC (p <.01). In conclusion, ML10302 and SR59768 share with cisapride a similar prokinetic action in the canine duodenum and jejunum in vivo. This effect is mediated by pathways involving activation of 5-HT4 and muscarinic receptors. Unlike cisapride, which induces tachycardia and prolongs the QTc by a mechanism probably unrelated to 5-HT4 receptor activation, ML10302 and SR59768 are devoid of cardiac effects in this model. (+info)
A simple high-performance liquid chromatography assay for the major cisapride metabolite, norcisapride, in human urine.
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A simple high-performance liquid chromatography assay using fluorescence detection for the major metabolite of the gastric prokinetic drug cisapride, norcisapride, is presented. Analysis is performed using an Alltech Platinum EPS C8 column with a mobile phase made up of methanol and 0.02M sodium dihygrogen phosphate (45:55, v/v) containing triethylamine (1 g/L). Complete resolution is achieved among norcisapride, the internal standard (metoclopramide), and endogenous urinary components. The assay is linear over the range 50-2000 ng/mL with a mean recovery of 71.2% across the analytical range following solvent extraction with toluene-isoamyl alcohol (95:5, v/v). Intraday coefficients of variation (precision) determined at 200 and 1000 ng/mL are 6.0 and 9.8%, respectively, and interday coefficients of variation are 8.8 and 6.6%, respectively. Intra- and interassay accuracy (as mean relative error) determined at the same concentrations is within 10% in all cases. An analysis of urine samples from a healthy volunteer following the administration of a single 10-mg oral dose of cisapride is shown. (+info)
Clinical considerations in GERD (gastroesophageal reflux disease) therapy: focus on cisapride.
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Heartburn, the major symptom of gastrointestinal reflux disease (GERD), is a common condition that is usually self-treated with over-the-counter products. For patients with severe or recurrent symptoms of GERD, pharmacologic therapy includes acid suppression with H2-receptor antagonists and proton pump inhibitors, and, alternatively, the use of prokinetic agents. While all of these are efficacious, given its high efficacy in nonerosive and mild-to-moderate erosive esophagitis, the prokinetic agent cisapride deserves significant consideration in this patient population. (+info)
Identification of SK-951, a novel benzofuran derivative, as an agonist to 5-HT4 receptors.
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The pharmacological profile of SK-951 ((-)4-amino-N-[2-(1-azabicyclo[3.3.0]octan-5-yl) ethyl]-5-chloro-2,3-dihydro-2-methylbenzo[b]furan-7-carboxamide hemifumarate) was identified in relation to serotonin 5-HT3 and 5-HT4 receptors by the receptor binding assay and functional studies. The receptor binding assay showed that SK-951 bound to the 5-HT3 receptor with a high affinity, to the 5-HT4 receptor with relatively higher affinity and to the muscarinic M2 receptor with a low affinity, but not to dopamine D1 and D2 and serotonin 5-HT1 and 5-HT2 and muscarinic M1 and M3 receptors. SK-951 caused relaxations of tunica muscularis mucosae preparations from rat esophagus which were precontracted with carbachol, and the effects were antagonized by GR113808, a selective 5-HT4 antagonist. In the longitudinal muscle with myenteric plexus (LMMP) preparations from guinea pig ileum, SK-951 enhanced the electrically-stimulated contraction of preparations in which the 5-HT1, 5-HT2 and 5-HT3 receptors were blocked, and it enhanced the electrically-stimulated release of [3H]acetylcholine (ACh). These effects of SK-951 were antagonized by GR113808. SK-951 inhibited the 5-HT3 receptor-mediated contractions. These results indicate that SK-951 possesses properties of an agonist for the 5-HT4 receptor and an antagonist for the 5-HT3 receptor. Thus, SK-951 is a new and potent 5-HT4-receptor agonist and causes contractions of guinea pig ileum mediated by enhancement of ACh release via the 5-HT4 receptor. (+info)
Randomised controlled trial of cisapride in preterm infants.
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AIM: To determine the effect of cisapride on gastrointestinal motility in preterm infants. METHODS: Cisapride (0.2 mg/kg, 8 hourly ) or placebo was given first for seven days in a double blind randomised crossover study of 10 preterm infants. Gastrointestinal motility was assessed on day 3 of each treatment. The half gastric emptying time (GET1/2) was determined by using ultrasonography to measure the decrease in the gastric antral cross sectional area after a feed. The whole gastrointestinal transit time (WGTT) was assessed by timing the transit of carmine red through the gut. Treatments were compared using the Wilcoxon matched pairs signed ranks test. RESULTS: Median (range) birthweight was 1200 (620, 1450) g and postconceptional age 33 (29, 34) weeks at recruitment. GET1/2 was significantly longer during cisapride treatment than during placebo; the median of the differences (95% confidence interval) was 19.2 (11, 30 minutes, p=0.008). WGTT was also longer during cisapride treatment, but the difference was not significant; the median of the differences was 11(-18, 52 hours, p=0.1). CONCLUSIONS: Cisapride delays gastric emptying and may delay WGTT in preterm infants. Its use to promote gastrointestinal motility in this group cannot be recommended. (+info)
The effect of cisapride on duodenal acid exposure in the proximal duodenum in healthy subjects.
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AIM: To investigate the effect of the prokinetic drug, cisapride, on fasting and postprandial acid exposure in the proximal duodenum. METHODS: Using a double-blind, placebo-controlled crossover study design, 12 healthy male volunteers were studied. After 1 week of dosing (cisapride 20 mg b.d. orally or placebo), fasting and postprandial antroduodenal pH-and pressure-recordings were made. Using a small-caliber (4 mm) catheter, containing one antral and two duodenal pH electrodes, and two antral and three duodenal pressure recording sites. Transmucosal potential difference was measured to ensure proper catheter position. Infusions of 0.1 N HCl were given in the duodenal bulb. RESULTS: Endogenous acidification of the duodenal bulb occurred more frequently during phase II and postprandially, compared to phase I (P<0.001). During phase I, alkalinization of the antrum was observed. Cisapride significantly increased the postprandial number of duodenal acidic periods (P<0.02), but shortened their duration (P<0.04). The duodenal motor response elicited by exogenous acid was lower during phase I (P<0.05). CONCLUSIONS: Antral and proximal duodenal acidity vary with the phases of the interdigestive motor complex. Cisapride shortens the individual periods of duodenal acidification. (+info)
Duodenogastric reflux: clinical and therapeutic aspects.
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BACKGROUND: Duodenogastric reflux is believed to cause damage to gastric mucosa. Most reports on this disorder concern adult patients. PATIENTS AND METHODS: 1120 children with abdominal pain were studied; endoscopic features of duodenogastric reflux were found in 92 patients. To confirm the diagnosis of duodenogastric reflux, cholescintigraphy (Tc99-HEPIDA) was performed. Children with confirmed duodenogastric reflux by scintigraphy were given a prokinetic drug (cisapride). RESULTS: Endoscopic features of duodenogastric reflux were found in 92 children; the diagnosis was confirmed by scintigraphy in 59 patients. There was no significant difference in the severity of inflammation in gastric mucosa compared with the control group, whereas significantly fewer of these patients were infected with Helicobacter pylori. There was no correlation between regions of isotope accumulation and inflammatory lesions in the stomach. The prokinetic drug (cisapride) helped eliminate or greatly reduce duodenogastric reflux in children. CONCLUSIONS: When endoscopic features of duodenogastric reflux are found the final diagnosis should be based on an examination that does not itself influence the motility of the gastrointestinal tract: cholescintigraphy seems to be a useful method. However, because the use of milk as a test meal affects the scintigraphic image, there was no correlation between the area of isotope accumulation and the localisation of inflammatory lesions in the stomach. Duodenogastric reflux seems to be less important as a cause of inflammatory lesions than other factors (such as genetic predisposition, stress, etc). Prokinetic drugs have a beneficial influence on treatment results in children with inflammatory lesions of gastric mucosa with duodenogastric reflux. (+info)