Peripheral mechanisms of sibutramine involving proximal gastric motility in dogs.

OBJECTIVE

Sibutramine, a serotonin-norepinephrine uptake inhibitor, has been used for treating obesity. However, its possible mechanisms involving gastric motility have not been reported. The aim of this study was to evaluate the effects of sibutramine on gastric accommodation and antral motility.

RESEARCH METHODS AND PROCEDURES: The study was performed in seven dogs with a stomach cannula and composed of two separate experiments: antral contractions and gastric tone. Each experiment included two sessions on 2 separate days in a randomized order: a control session and a treatment session with sibutramine (5 mg/kg per os) administrated 2 hours before the study.

RESULTS

Sibutramine significantly increased fasting gastric tone; the gastric volume in the fasting state at baseline was 103.8 +/- 12.3 mL and significantly decreased to 35.3 +/- 16.0 mL with sibutramine (p = 0.0075). Sibutramine also impaired gastric accommodation. The average postprandial gastric volume was 472.1 +/- 16.7 mL in the control session and reduced to 302.2 +/- 53.6 mL with sibutramine (p = 0.013). The average postprandial increase in gastric volume during the 60-minute postprandial period with sibutramine was significantly lower than the corresponding values in the control session: 266.8 +/- 46.1 vs. 393.9 +/- 15.3 mL (p = 0.03). Sibutramine had no effects on postprandial antral contractions.

DISCUSSION: Sibutramine increases gastric tone and impairs gastric accommodation to an orally ingested meal. The inhibitory effect of sibutramine on gastric accommodation may partially explain the reduced food intake with sibutramine in patients with obesity.