JOURNAL ARTICLE
REVIEW

The endocannabinoid system and rimonabant: a new drug with a novel mechanism of action involving cannabinoid CB1 receptor antagonism—or inverse agonism—as potential obesity treatment and other therapeutic use

S Xie, M A Furjanic, J J Ferrara, N R McAndrew, E L Ardino, A Ngondara, Y Bernstein, K J Thomas, E Kim, J M Walker, S Nagar, S J Ward, R B Raffa
Journal of Clinical Pharmacy and Therapeutics 2007, 32 (3): 209-31
17489873
There is considerable evidence that the endocannabinoid (endogenous cannabinoid) system plays a significant role in appetitive drive and associated behaviours. It is therefore reasonable to hypothesize that the attenuation of the activity of this system would have therapeutic benefit in treating disorders that might have a component of excess appetitive drive or over-activity of the endocannabinoid system, such as obesity, ethanol and other drug abuse, and a variety of central nervous system and other disorders. Towards this end, antagonists of cannabinoid receptors have been designed through rational drug discovery efforts. Devoid of the abuse concerns that confound and impede the use of cannabinoid receptor agonists for legitimate medical purposes, investigation of the use of cannabinoid receptor antagonists as possible pharmacotherapeutic agents is currently being actively investigated. The compound furthest along this pathway is rimonabant, a selective CB(1) (cannabinoid receptor subtype 1) antagonist, or inverse agonist, approved in the European Union and under regulatory review in the United States for the treatment of obesity. This article summarizes the basic science of the endocannabinoid system and the therapeutic potential of cannabinoid receptor antagonists, with emphasis on the treatment of obesity.

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