CB1 receptor inverse agonist pharmacotherapy for metabolic disorders

Abstract

The cannabinoid-1 receptor (CB1R) has been implicated in the control of energy balance based on its anatomical localization, the interaction among the endocannabinoid system and other transmitter systems, and the appetite-enhancing effect of tetrahydrocannabinol. Recent development of CB1R inverse agonists indicated that these agents inhibit food intake, increase energy expenditure, and reduce fat mass. This article reviews the preclinical and clinical efficacy of several CB1R inverse agonists and provides a perspective on the use of CB1R inverse agonists in studies of obesity and metabolic disorders. The compounds reviewed here are no longer in clinical development for obesity. Drug Dev Res 70 : 566-576, 2009.