JOURNAL ARTICLE

Cannabinoid CB(2)-selective inverse agonist protects against antigen-induced bone loss

Charles A Lunn, Jay Fine, Alberto Rojas-Triana, James V Jackson, Brian Lavey, Joseph A Kozlowski, R William Hipkin, Daniel J Lundell, Loretta Bober
Immunopharmacology and Immunotoxicology 2007, 29 (3): 387-401
18075852
Work to improve the therapeutic properties of cannabinoid CB(2) receptor-selective inverse agonists has led to the development of Sch.036, an aryl substituted triaryl bis-sulfone with improved oral pharmacokinetic parameters. In this report, we show that this compound blocks in vivo trafficking of various leukocyte populations, a property consistent with other members of this chemical series. This CB(2)-selective compound also shows efficacy in leukocyte recruitment models when added in concert with suboptimal doses of selected anti-inflammatory agents, consistent with its unique function and indicative of its potential therapeutic utility. Finally, studies with Sch.036 show that this cannabinoid CB(2)-specific inverse agonist can ameliorate bone damage in a rat model of relapsing-remitting arthritis. This result suggests that a cannabinoid CB(2)-selective inverse agonist may help ameliorate a particularly harmful property of this inflammatory joint disease.

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