Safety evaluation and treatment affect of LY2190416, a CB-1 antagonist/inverse agonist in growing beagle dogs

Abstract

The objective of this study was to assess the safe use of LY2190416, a cannabinoid receptor 1 receptor antagonist/inverse agonist, for obesity management in dogs. Twenty-four clinically normal young beagle dogs were administered LY2190416 at doses of 3, 9, or 18 mg/kg or placebo, orally, once daily for 13 weeks. Food consumption and body weight were determined, and dogs were evaluated for changes in hematology, clinical chemistry, urinalysis, and serum cortisol. LY2190416 had no significant effect on hematology, clinical chemistry, urinalysis, and serum cortisol. All dogs consumed 100% of their entire daily allowance throughout the study. All dogs gained weight during the study, but treated dogs gained less than control dogs by the end of the study. During the first month, dogs exhibited a dose-dependent decrease in rate of weight gain (19.7 g/day for control dogs vs. 10.6 g/day for the 18 mg/kg dose group). LY2190416 was found to be safe at doses up to 18 mg/kg administered daily for 3 months. Results suggest that LY2190416 decreases rate of weight gain without affecting appetite or causing significant adverse health effects in normal growing dogs. Possible mechanisms for a proposed metabolic effect are discussed.