Peripheral Effects of Rimonabant on Upper Gastrointestinal Motility

Abstract

Background: Rimonabant (SR 141716A) is an antagonist-inverse agonist of cannabinoid receptor 1 (CB1), which was developed for the obesity treatment. The aim of this study was to investigate effects of rimonabant on gastric emptying, gastric tone, accommodation and compliance, antral contractions and small intestinal contractions in dogs. Materials and Methods: Six dogs were equipped with a duodenal cannula for the measurements of gastricemptying, small bowel contractions and small bowel slow waves. Another six dogs were equipped with a gastric cannula for the measurements of gastric tone, accommodation and compliance, antral contractions and gastric slow waves. Each of the measurements was obtained in one control and two rimonabant sessions (different doses). Results: 1) Rimonabant accelerated gastric emptying of liquids and the effect was more potent at a dose of 1 mg/kg than 0.5 mg/kg; 2) Rimonabant increased gastric tone and reduced gastric compliance and accommodation with the 1.0 mg/kg dose being more potent; 3) Rimonabant inhibited antral contractions; 4) Rimonabant increased small intestinal contractions. The small intestinal contraction index was 9.60 ± 2.44 in the control session and increased to 12.35 ± 1.45 with rimonabant 0.5mg/kg (p=0.018 vs. control) and 14.75 ± 2.46 with rimonabant 1 mg/kg (p=0.008 vs. control). Conclusions: Rimonabant reduces gastric compliance and accommodation, inhibits antral contractions but increases intestinal motility. These findings suggest the peripheral mechanisms of rimonabant in reducing food intake and body weight.