Effects of cisapride on gastric emptying of oil and aqueous meal components, hunger, and fullness.

Jones, Karen L.; Horowitz, Michael; Carney, B. I.; Sun, W. M.; Chatterton, Barry E.

doi:10.1136/gut.38.3.310

Cited by 14 publications

(14 citation statements)

References 25 publications

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“…teract to modulate energy intake (11,20,31), studies in both humans and animals suggest that intestinal mechanisms are dominant (12,26,30,45).…”

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confidence: 98%

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confidence: 98%

“…lauric acid; decanoic acid; energy intake; gastrointestinal peptides; gastrointestinal contractile activity NUTRIENTS CONTROL APPETITE AND ENERGY INTAKE through two principal mechanisms arising from the stomach and small intestine: 1) inhibition of gastric emptying, which activates stretch receptors through an increase in gastric distension (1, 3); and 2) triggering of neural (29, 53) and humoral (21,36,42) signals as a result of the interaction of nutrients with the small intestine (38, 42). Although gastric and intestinal signals interact to modulate energy intake (11,20,31), studies in both humans and animals suggest that intestinal mechanisms are dominant (12,26,30,45).The effects of fat on appetite, gastrointestinal motility, and hormone release are dependent on digestion of triglycerides into free fatty acids (13,14,41,52). For example, in healthy subjects, inhibition of fat digestion by the lipase inhibitor tetrahydrolipstatin attenuates the effects of duodenal triglyceride on the perception of fullness (13, 14), energy intake (13, 41), antropyloroduodenal (APD) motor activity (13), and plasma cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1) concentrations (13, 52).…”

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Effects of intraduodenal fatty acids on appetite, antropyloroduodenal motility, and plasma CCK and GLP-1 in humans vary with their chain length

Feltrin¹,

Little²,

Meyer³

et al. 2004

American Journal of Physiology-Regulatory, Integrative and Comp

203

213

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The gastrointestinal effects of intraluminal fats may be critically dependent on the chain length of fatty acids released during lipolysis. We postulated that intraduodenal administration of lauric acid (12 carbon atoms; C12) would suppress appetite, modulate antropyloroduodenal pressure waves (PWs), and stimulate the release of cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1) more than an identical dose of decanoic acid (10 carbon atoms; C10). Eight healthy males (19-47 yr old) were studied on three occasions in a double-blind, randomized fashion. Appetite perceptions, antropyloroduodenal PWs, and plasma CCK and GLP-1 concentrations were measured during a 90-min intraduodenal infusion of 1) C12, 2) C10, or 3) control (rate: 2 ml/min, 0.375 kcal/min for C12/C10). Energy intake at a buffet meal, immediately after completion of the infusion, was also quantified. C12, but not C10, suppressed appetite perceptions (P < 0.001) and energy intake (control: 4,604 +/- 464 kJ, C10: 4,109 +/- 588 kJ, and C12: 1,747 +/- 632 kJ; P < 0.001, C12 vs. control/C10). C12, but not C10, also induced nausea (P < 0.001). C12 stimulated basal pyloric pressures and isolated pyloric PWs and suppressed antral and duodenal PWs compared with control (P < 0.05 for all). C10 transiently stimulated isolated pyloric PWs (P = 0.001) and had no effect on antral PWs but markedly stimulated duodenal PWs (P = 0.004). C12 and C10 increased plasma CCK (P < 0.001), but the effect of C12 was substantially greater (P = 0.001); C12 stimulated GLP-1 (P < 0.05), whereas C10 did not. In conclusion, there are major differences in the effects of intraduodenal C12 and C10, administered at 0.375 kcal/min, on appetite, energy intake, antropyloroduodenal PWs, and gut hormone release in humans.

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“…teract to modulate energy intake (11,20,31), studies in both humans and animals suggest that intestinal mechanisms are dominant (12,26,30,45).…”

mentioning

confidence: 98%

mentioning

confidence: 98%

mentioning

confidence: 99%

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Effects of intraduodenal fatty acids on appetite, antropyloroduodenal motility, and plasma CCK and GLP-1 in humans vary with their chain length

Feltrin¹,

Little²,

Meyer³

et al. 2004

American Journal of Physiology-Regulatory, Integrative and Comp

203

213

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Section: Pharmacodynamicsmentioning

confidence: 99%

“…In healthy volunteers cisapride accelerated gastric emptying of liquids 31,32 and solids 33 and was also capable of reversing the delay in emptying induced by fat instillation into the duodenum 34 . In one study in healthy volunteers, cisapride acceleration of the oil and aqueous components of a mixed olive oil and soup meal was associated with an increase in preprandial hunger and a reduction in postprandial fullness 32 . In disease states, cisapride was shown to accelerate gastric emptying in FD, 35,36 postsurgical, 35 diabetic 19,30,35,37–40 and idiopathic gastroparesis, 33,40–42 as well as gastric emptying delay related to anorexia nervosa, 43 CIIP, 36,41 critical illness 44 and GERD 45 .…”

Section: Pharmacodynamicsmentioning

confidence: 99%

Cisapride: What can we learn from the rise and fall of a prokinetic?

Quigley

2011

J of Digest Diseases

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Cisapride, the prototype serotonergic agent, evolved from a body of research that defined the key roles of serotonergic receptors in gastrointestinal motor and sensory function. Impressed by its in vitro properties and encouraged by clinical trial data, cisapride became the drug of choice for the treatment of a wide range of motility disorders and clinicians appeared impressed by its efficacy and comfortable with its side-effect profile. Once serious cardiac events began to be reported in association with cisapride therapy, dark clouds rapidly gathered and soon enveloped the drug, leading to its widespread withdrawal from markets. What lessons can we learn from the story of cisapride? How can its brief but spectacular rise and equally sensational demise inform the development of new drugs which are so sorely needed in the management of motility and functional gastrointestinal disorders? This review explores the background to the development of cisapride, its history in clinical trials and the experience with adverse events and, in so doing, attempts to identify lessons for the future in the therapeutics of enteric neuromodulatory drugs.KEY WORDS: cisapride, gastroesophageal reflux, gastrointestinal motility, gastroparesis, prokinetic, serotonin.Cisapride, introduced worldwide in the 1990s, is a serotonin 5-HT4 agonist with 5-HT3 antagonist activity that stimulates the release of acetylcholine from postsynaptic neurons in the enteric nervous system. It therefore had quite widespread prokinetic effects throughout the gastrointestinal tract: stimulating salivary secretion, increasing esophageal peristaltic amplitude, augmenting lower esophageal sphincter pressure, enhancing gastric emptying and stimulating small bowel and colonic transit. It was, however, devoid of antidopaminergic and direct cholinomimetic effects; the former avoiding the central nervous system and hyperprolactinemia-related side effects of metoclopramide, the latter avoiding the bladder and other side effects of traditional cholinergics, such as bethanechol. Though ultimately employed in a wide range of motility disorders from gastroparesis and pseudo-obstruction to colonic inertia, cisapride was actually approved by the Food and Drug Administration (FDA) in the USA for nocturnal heartburn based on the results of pivotal clinical trials. In primary care, cisapride soon came to be prescribed, either on its own or in combination with a histamine H2 receptor antagonist or a proton pump inhibitor, for a range of upper gastrointestinal symptoms including heartburn and dyspepsia. Its use was especially advocated for children with gastroesophageal reflux disease (GERD) based on the premise that dysmotility was predominant in the etiology of reflux in this patient population. Though trials in gastroparesis did not always show a consistent relationship between symptom improvement and an enhanced gastric emptying rate,

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