化合物 SR144528

Ki: 0.6 nM (CB2 receptor)

SR144528 is a potent and selective CB2 receptor antagonist with a K _i of 0.6 nM. SR144528 alone is able to stimulate in a concentration-dependent manner (EC ₅₀ =26±6 nM, two experiments) the forskolin-sensitive adenylyl cyclase activity in CHO-CB2 cells with a maximum effect at 1 μM (4-fold stimulation) whereas at this concentration it has no significant effect on CHO-CB1 cells (15% inhibition). Raw 264.7 macrophages supplemented with SR144528 display reduced caspase-3 activity. SR144528 inhibits microsomal acyl-coenzymeA:cholesterol acyltransferase (ACAT) activity in a concentration-dependent manner with an IC ₅₀ value of 3.6±1.1 μM. At 10 μM, SR144528 inhibits ACAT activities ~68%.

No effect on the binding of [ ³ H]-CP 55,940 to its specific sites in the brain is observed after either oral (up to 10 mg/kg) or i.c.v. (10 μg/animal) administration of SR144528 in mice. The occupancy by SR144528 of the spleen cannabinoid receptor is time-dependent and significant for at least 18 hours after oral administration at 3 mg/kg. SR144528 does not induce any significant effect on gastrointestinal (GI) motility when given alone. SR144528 does not block but enhances delayedgastric emptying.