The newly recognized class of
5-hydroxytryptamine receptors (5HT3) may be involved in the induction of
nausea, since their pharmacological antagonists are effective against
emesis induced by
chemotherapy. 5HT3 receptors are present on enteric neurons, and 5HT3 blockers may produce mild
constipation; we thus hypothesized that 5HT3 receptors would modulate colonic motility. To determine if
GR 38032F, a selective 5HT3 antagonist known to have
antiemetic effects, influences colonic transit in health, a randomized, double-blind, placebo-controlled crossover study was performed. Using a radiopaque marker technique, colonic transit was quantified in 39 healthy volunteers (19 men, 20 nonpregnant women) 18-70 years of age. On a standard 25-g fiber diet, 16 mg of
GR 38032F was given orally thrice daily. Gastrointestinal
peptides (
peptide YY, human
pancreatic polypeptide,
neurotensin,
motilin,
gastrin-
cholecystokinin,
substance P) were also measured in plasma fasting and postprandially. Mean total colonic transit time on placebo was 27.8 hr, while on
GR 38032F it was 39.1 hr (P less than 0.0005). Transit times through the left colon (P less than 0.0005) and rectosigmoid (P less than 0.05) were prolonged by the
drug, but right colonic transit was not significantly altered. Transit times did not correlate with age or gender, but subjects with shorter transit times were significantly more affected than were those with longer transit times. The peak release of
peptide YY was minimally decreased following
GR 38032F (P less than 0.01), but the peak and integrated postprandial responses of human
pancreatic polypeptide,
neurotensin,
motilin,
gastrin-
cholecystokinin, and
substance P were not significantly altered by the
drug.(ABSTRACT TRUNCATED AT 250 WORDS)