CB-1 antagonism with LY2190416 results in acute weight loss in obese adult dogs fed a high-fat diet

Newhall, Karina; Nunamaker, Elizabeth A.; Gissendanner, S J; Thompson, C.; Owens, Julie A.; Lucas, A.; Sherman, J. G.

doi:10.1111/j.1365-2885.2010.01202.x

Cited by 1 publication

(3 citation statements)

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“…Dogs treated with LY2190416 consumed less over the course of the study than control dogs despite being fed an equivalent Kcal of food per kg body weight. Previous work with this drug in obese dogs using doses of 1–6 mg/kg has shown a significant but transient decrease in food intake relative to baseline and control animals (Newhall, et al . 2010).…”

Section: Discussionmentioning

confidence: 99%

“…In this study, LY2190416, a CB‐1 antagonist with confirmed inverse agonist activity, was administered to clinically normal young beagle dogs, subjectively judged to be of average body weight, to evaluate the safety of the molecule. The effect of this drug on food intake and body weight in ad libitum fed obese dogs was described in a previous report (Newhall et al. , 2010).…”

Section: Introductionmentioning

confidence: 88%

“…, 2010). In contrast to the previous study, this study design utilized a fixed feeding regimen where dogs received 120% of their daily energy requirement on a per kg basis to ensure adequate caloric intake and to counteract the expected compound induced decrease in appetite previously reported (Newhall et al. , 2010).…”

Section: Introductionmentioning

confidence: 99%

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

Nunamaker¹,

Newhall²,

Thompson³

et al. 2011

Journal of Veterinary Pharmacology and Therapeutics

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 88%