Biological Activity
a 804598 is a potent and selective antagonist of p2x7 receptor with ic50 values of 8.9, 9.9 and 10.9 nm for mouse, rat and human p2x7 receptors, respectively [1].p2x purinoceptor 7 (p2x7 receptor) is a purinoceptor and is activated by high concentrations of atp. p2x7 receptor plays an important role in atp-mediated cell death, inflammation and regulation of receptor trafficking.a 804598 is a potent and selective p2x7 receptor antagonist. in differentiated thp-1 cells that expressed human p2x7 receptors, a 804598 inhibited bzatp stimulated yo-pro uptake and release of il-1β. in 1321n1 cells expressed recombinant rat p2x7 receptor, a 804598 showed high affinity with kd = 2.4 nm [1]. a 804598 inhibited bz-atp stimulated calcium influx with ic50 value of 28.71 nm in a concentration-dependent way. a-804598 was a potent p2x7 receptor antagonist with ki value of 7.51 nm [2].in adult male rats, footshock increased the mrna levels of cd14 and il-1β in the paraventricular nucleus. while a-804598 (25 mg/kg) partially inhibited these effects [3].
References
[1]. donnelly-roberts dl, namovic mt, surber b, et al. [3h]a-804598 ([3h]2-cyano-1-[(1s)-1-phenylethyl]-3-quinolin-5-ylguanidine) is a novel, potent, and selective antagonist radioligand for p2x7 receptors. neuropharmacology, 2009, 56(1): 223-229.
[2]. able sl, fish rl, bye h, et al. receptor localization, native tissue binding and ex vivo occupancy for centrally penetrant p2x7 antagonists in the rat. br j pharmacol. 2011, 162(2): 405-414.
[3]. catanzaro jm1, hueston cm, deak mm, et al. the impact of the p2x7 receptor antagonist a-804598 on neuroimmune and behavioral consequences of stress. behav pharmacol, 2014, 25(5-6): 582-598.
