The effects of the specific 5HT4 receptor agonist, prucalopride, on colonic motility in healthy volunteers

Background: Prucalopride is a selective and specific 5-hydroxytryptamine(4) receptor agonist that is known to increase stool frequency and to accelerate colonic transit. Aim: To investigate the effect of prucalopride on high-amplitude propagated contractions and segmental pressure waves in healthy volunteers. Methods: After 1 week of dosing (prucalopride or placebo in a double-blind, randomized, crossover fashion), colonic pressures were recorded in 10 healthy subjects using a solid-state pressure catheter with six sensors spaced 10 cm apart. Subjects kept diary records of their bowel habits (frequency. consistency and straining). High-amplitude propagated contractions were analysed visually, comparing their total numbers and using 10-min time windows. Segmental pressure waves were analysed using computer algorithms, quantifying the incidence. amplitude, duration and area under the curve of all detected peaks. Results: When taking prucalopride, stool frequency increased, consistency decreased and subjects strained less. Prucalopride just failed to increase the total number of high-amplitude propagated contractions (P = 0.055). The number of 10-min time windows containing high-amplitude propagated contractions was increased by prucalopride (P = 0.019). Prucalopride increased the area under the curve per 24 h (P = 0.026). Conclusions: The 5-hydroxytryptamine(4) receptor agonist prucalopride stimulates high-amplitude propagated contractions and increases segmental contractions, which is likely to be the underlying mechanism of its effect on bowel habits in healthy volunteers.