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.
Highlights
Drugs that interfere with cannabinoid cannabinoid receptor 1 (CB1) receptor transmission suppress a number of food-related behaviours and these compounds are currently being assessed for their potential utility as appetite suppressants
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
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
Summary
Drugs that interfere with cannabinoid CB1 receptor transmission suppress a number of food-related behaviours and these compounds are currently being assessed for their potential utility as appetite suppressants. Further research showed that the effects of rimonabant on food intake and weight loss were associated with alteration of leptin expression in hypothalamus [3]. Therapies aimed at regulating the observed changes in GI motility are being actively explored and applied clinically in the management of obese patients [7]. Rimonabant was reported to accelerate gastric emptying and small intestine transit in a number of rodent studies [5,8]. There is no systematic study investigating the effects of rimonabant on GI motility, including gastric tone, accommodation, compliance, antral contraction and small intestinal transit in animals or humans. 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
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