GR 38032F (Ondansetron), a selective 5HT3 receptor antagonist, slows colonic transit in healthy man

Abstract

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)

The Function of 5‐HT3 Receptors on Colonic Transit in Rats

“…Few studies on the effects of 5-HT3 receptor antagonists on the colonic motor function have been reported (16,19). In these studies, 5-HT3 receptor antagonists slow the colonic transit in human, both healthy subjects and irritable bowel syndrome (IBS) patients.…”

Outpatient total body irradiation prior to bone marrow transplantation in pediatric patients: a feasibility analysis

“…Constipation is also common and the drug has been noted to lead to an increase in gastrointestinal transit time in healthy volunteers. 10 In conclusion, outpatient TBI prior to BMT is feasible and preferable to inpatient therapy.…”

Direct Subunit-Dependent Multimodal 5-Hydroxytryptamine3Receptor Antagonism by Methadone

“…Single channels mediated by 5-HT 3 receptors in enteric neurons have conductances similar to those of 5-HT 3AB receptors (Galligan, 2002). Therefore 5-HT 3AB receptors are located peripherally where they are likely to participate in the gastrointestinal effects of the setrons, which cause increased colonic transit time (Talley et al, 1990). Thus, antagonists with selectivity for homomeric 5-HT 3A receptors may have fewer peripheral side effects.…”