Influence of the 5-HT3 receptor antagonist ondansetron on gastric sensorimotor function and nutrient tolerance in healthy volunteers

Neurogastroenterol Motil. 2011 May;23(5):444-9, e175. doi: 10.1111/j.1365-2982.2010.01655.x. Epub 2010 Dec 29.

Abstract

Background: Serotonin is believed to be involved in the regulation of the gastric accommodation reflex in man however which receptor subtype(s) are involved remains to be elucidated.

Methods: Eleven healthy subjects (nine men, age 19-30) underwent a gastric barostat and a drinking test after treatment with either placebo or ondansetron (8 mg intravenously). During the barostat protocol an intragastric flaccid bag was stepwise distended (2 mmHg increments 2 min) to determine gastric compliance and sensitivity to distention. Subsequently, the pressure level was set at intra-abdominal pressure +2 mmHg while volume was followed before and after administration of a liquid meal (200 mL; 300 kcal). During the drink test volunteers drank at a rate of 15 mL min(-1) until maximal satiation. Results (mean ± SEM) were compared using t-tests and mixed model analysis.

Key results: Gastric compliance was not significantly altered by ondansetron (51.5 ± 5.6 vs 49.2 ± 5.2 mL mmHg(-1)), neither were the pressure thresholds for first perception or discomfort. Ondansetron treatment did not affect basal gastric tone (173 ± 14 vs 156 ± 12 mL), neither did it affect the amplitude of the meal-induced relaxation (160 ± 52 vs 131 ± 43 mL) or the maximum volume increase after the meal (264 ± 54 mL vs 234 ± 51 mL). During the drinking test the amount of liquid meal ingested at maximum satiation was significantly increased by ondansetron (784 ± 74 vs 907 ± 64 mL, P < 0.05).

Conclusions & inferences: These data suggest that 5-HT acting at 5-HT(3) receptors is not involved in the control of gastric sensorimotor function, but contributes to the regulation of hunger and satiation in man.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Cross-Over Studies
  • Double-Blind Method
  • Drinking
  • Eating / physiology*
  • Fasting
  • Female
  • Humans
  • Hunger / drug effects
  • Male
  • Ondansetron / pharmacology*
  • Placebos
  • Postprandial Period
  • Receptors, Serotonin, 5-HT3 / metabolism*
  • Satiation / drug effects
  • Serotonin / metabolism
  • Serotonin Antagonists / pharmacology*
  • Stomach / anatomy & histology
  • Stomach / drug effects*
  • Stomach / physiology*
  • Young Adult

Substances

  • Placebos
  • Receptors, Serotonin, 5-HT3
  • Serotonin Antagonists
  • Serotonin
  • Ondansetron