Journal article

Characterization of a novel, brain-penetrating CB1 receptor inverse agonist: metabolic profile in diet-induced obese models and aspects of central activity

Laura H Jacobson, S Renee Commerford, Sarah P Gerber, Yu Alice Chen, Beatriz Dardik, Frederique Chaperon, Chad Schwartzkopf, Nguyen-Tran Van, Thomas Hollenbeck, Peter McNamara, Xiaohui He, Hong Liu, H Martin Seidel, Anne-Liese Jaton, Jesper Gromada, Sandra Teixeira



Pharmacologic antagonism of cannabinoid 1 receptors (CB1 receptors) in the central nervous system (CNS) suppresses food intake, promotes weight loss, and improves the metabolic profile. Since the CB1 receptor is expressed both in the CNS and in peripheral tissues, therapeutic value may be gained with CB1 receptor inverse agonists acting on receptors in both domains. The present report examines the metabolic and CNS actions of a novel CB1 receptor inverse agonist, compound 64, a 1,5,6-trisubstituted pyrazolopyrimidinone. Compound 64 showed similar or superior binding affinity, in vitro potency, and pharmacokinetic profile compared to rimonabant. Both compounds improved the metabolic profile i..

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