Background:

Ki= 0.6 nM

SR 144528 is a CB2 receptor inverse agonist.

The CB2 receptor is principally expressed in immune tissue where it is involved in cannabinoid-mediated immune responses, but CB2 mRNA has been detected in mouse cerebellar cells and cerebellum and in rat microglial cells.

In vitro: SR 144528 displayed subnanomolar affinity for both the rat spleen and cloned human CB2 receptors and had a 700-fold lower affinity for both the rat brain and cloned human CB1 receptors. Moreover, SR 144528 showed no affinity for more than 70 receptors, ion channels or enzymes tested. SR 144528 could antagonize the inhibitory effects of the cannabinoid receptor agonist CP 55,940 on forskolin-stimulated adenylyl cyclase activity in cell lines expressing the human CB2 receptor but not in cells expressing the human CB1. In addition, SR 144528 could selectively block the mitogen-activated protein kinase activity that was induced by CP 55,940 in cell lines expressing human CB2 while an IC50 value of more than 1 μM was observed in cells expressing human CB1 [1].

In vivo: Animal study showed that oral administration of SR 144528 could totally displace the ex vivo [3H]-CP 55,940 binding to mouse spleen membranes with a long action duration. Whereas, after the oral route SR 144528 did not interact with the cannabinoid receptor expressed in the mouse brain CB1 [1].

Clinical trial: Up to now, SR 144528 is still in the preclinical development stage.

Reference:
[1] Rinaldi-Carmona M et al.  SR 144528, the first potent and selective antagonist of the CB2 cannabinoid receptor. J Pharmacol Exp Ther. 1998 Feb;284(2):644-50.