The effects of the specific 5HT(4) 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.


OBJECTIVE
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.
De Schryver
A M P
AM
Department of Gastroenterology, Gastrointestinal Research Unit, University Medical Center, Utrecht, The Netherlands. a.deschryver@digd.azu.nl
Andriesse
G I
GI
Samsom
M
M
Smout
A J P M
AJ
Gooszen
H G
HG
Akkermans
L M A
LM
D000328:Adult; D000368:Aged; D001572:Benzofurans / Q000494:pharmacology*; D018592:Cross-Over Studies; D003672:Defecation / Q000187:drug effects; D004311:Double-Blind Method; D005243:Feces / Q000737:chemistry; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017366:Serotonin Receptor Agonists / Q000009:adverse effects / Q000494:pharmacology*
D001572:Benzofurans; D017366:Serotonin Receptor Agonists; C406662:prucalopride