Preclinical toxicity evaluation of JD5037, a peripherally restricted CB₁ receptor inverse agonist, in rats and dogs for treatment of nonalcoholic steatohepatitis.

ABSTRACT: JD5037 is a novel peripherally restricted CB₁ receptor (CB₁R) inverse agonist being developed for the treatment of visceral obesity and its metabolic complications, including nonalcoholic fatty liver disease and dyslipidemia. JD5037 was administered by oral gavage at 10, 40, and 150 mg/kg/day dose levels for up to 34 days to Sprague Dawley rats, and at 5, 20, and 75 mg/kg/day dose levels for 28 consecutive days to Beagle dogs. In rats, higher incidences of stereotypic behaviors were observed in 10 mg/kg females and 40 mg/kg males, and slower responses for reflex and sensory tests were observed only in males at 10 and 40 mg/kg during neurobehavioral testing. Sporadic minimal incidences of decreased activity (males) and seizures (both sexes) were observed in rats during

SUBMITTER: Kale VP 

PROVIDER: S-EPMC7017916 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature