Cannabinoid CB2-Selective Inverse Agonist Protects Against Antigen-Induced Bone Loss

Work to improve the therapeutic properties of cannabinoid CB₂ 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 CB₂-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 CB₂-specific inverse agonist can ameliorate bone damage in a rat model of relapsing-remitting arthritis. This result suggests that a cannabinoid CB₂-selective inverse agonist may help ameliorate a particularly harmful property of this inflammatory joint disease.