Disease relevance of cisapride

• Cisapride and fatal arrhythmia [1].
• Participants were then stratified according to their initial grade of esophagitis and randomly assigned to 12 months of treatment with one of the following: cisapride (10 mg three times a day), ranitidine (150 mg three times a day), omeprazole (20 mg per day), ranitidine plus cisapride (10 mg three times a day), or omeprazole plus cisapride [2].
• CONTEXT: Cisapride, an oral prokinetic drug indicated for the symptomatic treatment of nocturnal heartburn due to gastroesophageal reflux disease, was approved by the US Food and Drug Administration in July 1993 [3].
• Cisapride in postoperative gastroparesis [4].
• Impaired transit of chyme in chronic intestinal pseudoobstruction. Correction by cisapride [5].

Psychiatry related information on cisapride

• Effects of cisapride on jejunal motor activity in fasting healthy humans [6].
• We concluded that intravenous cisapride accelerates gastric emptying and increases antral contraction amplitude in patients with anorexia nervosa [7].
• When cisapride was given, there was frequent irregular contractile activity, faster gastric emptying, and no symptoms of lethargy [8].
• Intestinal pseudoobstruction occurs in two phases: an early, neuropathic phase may respond to prokinetic drugs (metoclopramide, cisapride, octreotide, and erythromycin) and dietary modification (low-residue diets, vitamin supplementation) [9].
• The final number of spontaneous bowel movements, fecal soiling episodes, laxatives used, or percent patients with encopresis was not different when patients receiving cisapride were compared with those receiving placebo [10].

High impact information on cisapride

• Generalized sympathetic and vagal dysfunctions influence the response of patients with neuropathic chronic intestinal motility disorder to two doses of cisapride [11].
• Cisapride induced some changes in motor activity but did not accelerate the recovery of normal motility [12].
• They were treated with rectal cisapride (30 mg three times daily) or placebo until the clinical resolution of ileus [12].
• Statistical analysis compared symptom response among treatment and autonomic dysfunction groups and assessed the influence of absence of migrating motor complexes and presence of postprandial antral hypomotility on symptomatic responses to cisapride [11].
• Cisapride improves gallbladder contractility and bile lipid composition in an animal model of gallstone disease [13].

Chemical compound and disease context of cisapride

• The serotonin4 (5-HT4) receptor agonists cisapride and/or metoclopramide have been shown to stimulate cortisol secretion in some patients with ACTH-independent bilateral macronodular adrenal hyperplasias (AIMAH) causing Cushing's syndrome [14].
• OBJECTIVE: To investigate the relationship between duodenojejunal motor activity and glucose absorption and to evaluate the effect of modification of duodenojejunal motility on glucose absorption by using the prokinetic drug cisapride [15].
• Newer antiemetics with prokinetic properties (e.g. metoclopramide, domperidone and cisapride) have also been introduced in the management of gastrointestinal motility disturbances, and new anti-inflammatory salicylates (e.g. olsalazine and mesalazine) have been developed for the treatment of chronic inflammatory bowel diseases [16].
• CONCLUSION: In patients with severe gastro-oesophageal reflux disease both cisapride and ranitidine demonstrably lower oesophageal acid exposure, but neither therapy predictably normalizes it [17].
• Domperidone is more effective than cisapride in children with diabetic gastroparesis [18].

Biological context of cisapride

• Cisapride facilitates gastric emptying in patients with upper gut dysmotility [19].
• The propulsive efficiency (i.e., number of peristalses and total amount of fluid ejected per unit of time) of isolated segments of ileum was enhanced by cisapride (100 nM to 3 microM) [20].
• The amplitude of fast nicotinic excitatory postsynaptic potentials recorded from S cells was increased by cisapride in the concentration range of 10 nM to 1 microM [20].
• Cisapride (10-300 nM) did not affect the membrane potential, resting properties, or active properties of S neurons [20].
• Cisapride inhibited I(Kr), the major time-dependent outward current elicited by short pulses (I[K250]) to low depolarizing potentials, in a concentration-dependent manner with an IC50 of 15 nmol/L (therapeutic levels, 50 to 200 nmol/L) [21].

Anatomical context of cisapride

• CONTEXT: Cisapride, a gastrointestinal tract promotility agent, can cause life-threatening cardiac arrhythmias in patients susceptible either because of concurrent use of medications that interfere with cisapride metabolism or prolong the QT interval or because of the presence of other diseases that predispose to such arrhythmias [22].
• Cisapride renders biliary lipid composition towards normal by enhancing gallbladder (and possibly intestinal) motility and cycling of the bile salt pool, thereby increasing bile salt secretion [13].
• These data indicate that cisapride facilitates cholinergic transmission in the myenteric plexus of guinea pig ileum and that this effect may be at least partially responsible for the increased propulsive efficiency observed in ileal segments [20].
• Transiently expressed in COS-7 cells, this receptor stimulates adenylyl cyclase activity and is sensitive to the benzamide derivative cisapride [23].
• Overall, 112 myocytes were exposed to seven concentrations of cisapride (10 nmol/L to 10 micromol/L) [21].

Associations of cisapride with other chemical compounds

• Mean gastric emptying of radiopaque markers, assessed by serial radiographs of the gastric region, was accelerated by metoclopramide and cisapride, but the difference reached significance only with cisapride (p less than 0.05) [24].
• RESULTS: Metoclopramide decreased the transit after laparotomy with or without mechanical stimulation, whereas cisapride increased it after all three operations [25].
• We examined the influence of serotonin and cisapride on ion transport across intestinal mucosa in vitro and studied the effect of cisapride on the response to serotonin [26].
• Effects of ranitidine and cisapride on acid reflux and oesophageal motility in patients with reflux oesophagitis: a 24 hour ambulatory combined pH and manometry study [27].
• METHODS: Part A compared the effects of placebo to four doses of a 5-HT(4) receptor antagonist (SB-207266) on the cisapride mediated increase in plasma aldosterone (a 5-HT(4) mediated response) and orocaecal transit in 18 subjects [28].

Gene context of cisapride

• All HERG channels had similar sensitivity to block by cisapride [29].
• On the other hand, cisapride strongly inhibited CYP3A4 and markedly inhibited CYP2C9 [30].
• Interaction of cisapride with the human cytochrome P450 system: metabolism and inhibition studies [31].
• RESULTS: The rate of biotransformation of cisapride was greater by recombinant CYP3A4 than by CYP3A7 (0.77 +/- 0.5 and 0.01 +/- 0.01 nmol metabolites formed in 24 h, respectively), whereas CYP1A1, 1A2, 2C8, 2C9 and 3A5 showed no activity [32].
• Formation rate of NORCIS from 10 microM cisapride in 14 HLMs was highly variable (range, 4.9-133.6 pmol/min/mg of protein) and significantly correlated with the activities of CYP3A (r = 0.86, P =. 0001), CYP2C19, and 1A2 [31].

Analytical, diagnostic and therapeutic context of cisapride

• DESIGN AND SETTING: Retrospective study of prescription claims from a managed care organization database for all patients with cisapride prescriptions between July 1993 and December 1998 [3].
• Five minutes after an activity front (phase III) they received, in random double-blind fashion, 10 mg of cisapride, 4 mg of cisapride, or saline placebo by intravenous injection [6].
• Opiate analgesia is a possible cause of these alterations, and cisapride is a potential therapy [12].
• In part 2, 10 patients entered a double blind cross over study of cisapride (8 mg intravenously) [33].
• Effect of cisapride on the gastrointestinal transit of a solid meal in normal human subjects [34].

References