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

N. J. Talley, S. F. Phillips, A. Haddad, L. J. Miller, C. Twomey, A. R. Zinsmeister, R. L. MacCarty, A. Ciociola

Research output: Contribution to journalArticle

154 Scopus citations

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<0.0005). Transit times through the left colon (P<0.0005) and rectosigmoid (P<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<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. We conclude that 5HT3 receptors may be involved in the regulation of colonic transit in healthy man.

Original languageEnglish (US)
Pages (from-to)477-480
Number of pages4
JournalDigestive diseases and sciences
Volume35
Issue number4
DOIs
StatePublished - Apr 1 1990

Keywords

  • 5HT antagonists
  • colonic transit
  • gastrointestinal peptides

ASJC Scopus subject areas

  • Physiology
  • Gastroenterology

Fingerprint Dive into the research topics of 'GR 38032F (Ondansetron), a selective 5HT<sub>3</sub> receptor antagonist, slows colonic transit in healthy man'. Together they form a unique fingerprint.

  • Cite this

    Talley, N. J., Phillips, S. F., Haddad, A., Miller, L. J., Twomey, C., Zinsmeister, A. R., MacCarty, R. L., & Ciociola, A. (1990). GR 38032F (Ondansetron), a selective 5HT3 receptor antagonist, slows colonic transit in healthy man. Digestive diseases and sciences, 35(4), 477-480. https://doi.org/10.1007/BF01536922