Abstract
Cannabinoid CB(1) receptor antagonists reduce body weight in rodents and humans, but their clinical utility as anti-obesity agents is limited by centrally mediated side effects. Here, we describe the first mixed CB(1) antagonist/CB(2) agonist, URB447 ([4-amino-1-(4-chlorobenzyl)-2-methyl-5-phenyl-1H-pyrrol-3-yl](phenyl)methanone), which lowers food intake and body-weight gain in mice without entering the brain or antagonizing central CB(1)-dependent responses. URB447 may provide a useful pharmacological tool for investigating the cannabinoid system, and might serve as a starting point for developing clinically viable CB(1) antagonists devoid of central side effects.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Anti-Obesity Agents / pharmacology
-
Benzyl Compounds / chemical synthesis*
-
Benzyl Compounds / pharmacology
-
Body Weight
-
Cannabinoids / antagonists & inhibitors*
-
Cannabinoids / chemistry*
-
Cerebellum / metabolism
-
Chemistry, Pharmaceutical / methods*
-
Drug Design
-
Feeding Behavior / drug effects
-
Humans
-
Inhibitory Concentration 50
-
Mice
-
Models, Chemical
-
Pyrroles / chemical synthesis*
-
Pyrroles / pharmacology
-
Rats
-
Receptors, Cannabinoid / metabolism
-
Weight Gain / drug effects
Substances
-
(4-amino-1-(4-chlorobenzyl)-2-methyl-5-phenyl-1H-pyrrol-3-yl)(phenyl)methanone
-
Anti-Obesity Agents
-
Benzyl Compounds
-
Cannabinoids
-
Pyrroles
-
Receptors, Cannabinoid