guanosine-5--o-(3-thiotriphosphate) and Pleurisy

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.

Topics: Animals; Antigens; Area Under Curve; Arthritis, Experimental; Bone Density Conservation Agents; Bone Resorption; Chemotaxis; Edema; Female; Guanosine 5'-O-(3-Thiotriphosphate); Hypersensitivity, Delayed; Indicators and Reagents; Ligands; Lipopolysaccharides; Mice; Pleurisy; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2; Sulfones