Colon motility and colo-anal reflexes in chronic idiopathic constipation. Effects of a novel enterokinetic agent cisapride

Abstract

Motor activity of the colon and reflex behaviour of the anal sphincters in normal subjects and in patients with idiopathic constipation were studied using a novel probe with 5 open-end tips to measure pressures, and 3 balloons for stimulation of the distal colon. Constipation appeared to be associated with an increased threshold of the inhibitory relaxation reflex of the internal anal sphincter (41.7 in normals and 65.7 in patients), and in particular with a blunted sensation of the defaecation urge (51.0 in normals and 112.8 in patients). Single-blind comparison with a placebo showed that cisapride, a new gastrointestinal prokinetic substance, had a significant effect on the sensation threshold, which normalized or improved in 15 out of the 16 patients studied.

Evidence against an acetylcholine releasing action of cisapride in the human colon.

“…Evidence for constipation affecting cholinergic mechanisms in the human gut has been described by Paskins et al (1982). In contrast to the findings of Reboa et al (1984), Lee et al (1984) did observe a stimulatory effect of cisapride in non-constipated volunteers. Enhancement of acetylcholine release, which has been shown in the guinea-pig ileum, may not explain the action of cisapride on the human colon in vivo.…”

“…Incubation and superfusion of individual taenia preparations were carried out in the same small volume bath which was fitted with vertical platinum wire electrodes (0.5 mm diameter) to allow electrical field stimulation of the tissue from a constant current stimulator. After 90 min taeniae were exposed to a low then a high dose of cisapride (0.4 and 4.1 ,uM The observations that cisapride stimulates human colonic motility in constipated patients is not unequivocal as the observed change although marked did not reach the accepted level of significance :P = 0.081; Reboa et al, 1984). However the compound did enhance colonic transit in volunteers (Lee et al, 1984).…”

“…In conclusion in vitro radiolabelling experiments using human sigmoid taenia coli muscle have failed to indicate an enhanced release of acetylcholine by cisapride. Reboa et al (1984) showed cisapride stimulated colonic motor activity in constipated, but not normal individuals. If this motor effect can be shown to be significant and reproducible it is possible that constipation affects the responsiveness of cholinergic nerves to cisapride.…”

“…The compound does not antagonise dopamine receptors, but it may enhance the release of acetylcholine (Van Nueten et al, 1983). Studies in volunteers (Lee et al, 1984) and patients with idiopathic constipation indicate a motor stimulating property of cisapride in the human large intestine (Reboa et al, 1984).…”

Effect of Cisapride on Gastric Emptying and Heal Transit Time of Balanced Liquid Meal in Healthy Subjects

“…These data confirm that cisapride significantly increases the speed of gastric emptying also in normal subjects. The lack of effect on intestinal transit could be explained by the interindividual variation observed in our experiments.Cisapride is a new prokinetic gastrointes tinal agent whose mechanism of action is thought to be via the release of acetylcholine from the myenteric plexus and possibly by blocking serotonin receptors without inter fering with dopaminergic receptors [1,2].Studies with animals and in man have shown cisapride to stimulate gastric empty ing [3][4][5][6] and correct the impaired small bowel transit time [7,8], although clinical research relating to the activity of the drug in normal subjects is very limited [9].Our purpose, therefore, was to simulta neously investigate the effect of cisapride on gastric emptying and on the ileal transit time of a balanced liquid meal in healthy sub jects. …”