CISAPRIDE STIMULATES HUMAN ESOPHAGEAL MOTILITY

The potency of cisapride to stimulate esophageal motility is still a m atter of conjecture. This double-blind placebo-controlled study assess ed the effect of repeated oral doses of cisapride at 10 and 20 mg on i nterdigestive esophageal motility in 10 healthy male volunteers. In ea ch experiment, esophageal motility was recorded continuously for 60 mi n with a sleeve sensor straddling the lower esophageal sphincter and f our series of 10 wet swallows being performed. Analysis of motor event s was computer assisted. Plasma cisapride levels amounted to 72.3 +/- 6.1 ng/ml with 10 mg cisapride and 142.5 +/- 11.9 ng/ml with 20 mg cis apride (p < 0.001 vs. 10 mg). Lower esophageal sphincter pressure incr eased from 20.6 +/- 2.3 mm Hg (placebo) to 28.9 +/- 2.3 mm Hg with 10 mg cisapride (p < 0.0001 vs. placebo) and to 26.8 +/- 1.8 mm Hg with 2 0 mg cisapride (p < 0.001 vs. placebo). Cisapride increased amplitude, duration, and area but not contractility and peristaltic velocity of esophageal contraction waves. Cisapride caused a maximum rise in ampli tude of 22.4%, in area of 19.4%, and in duration of 9.6%. Its effects were greatest in the proximal and middle smooth muscle segments and mo re pronounced with 10 than with 20 mg. We conclude that cisapride clea rly increases lower esophageal sphincter pressure and, to a lesser ext ent, raises amplitude and prolongs duration of esophageal contraction waves. Effects on contraction waves seem to correlate with the density of cholinergic innervation. Increasing the dose above 10 mg in the st eady state does not further enhance the effect in healthy subjects.