The platelet P2T receptor plays a major role in platelet aggregation, and its antagonists are suggested to have significant therapeutic potential as antithrombotic agents. AR-C 66096 is a novel, potent and selective antagonist at human platelet P2T-purinoceptors.
In vitro: In suspensions of human washed platelets, AR-C 66096 (1-100 nM) produced concentrationdependent rightward displacement of concentration-effect (E/[A]) curves obtained for ADP-induced platelet aggregation. The anti-aggregatory potency of AR-C 66096 was not influenced by increasing the incubation time from 2 to 15 min nor by inclusion of the P1-purinoceptor antagonist 8-sulphophenyltheophylline at a concentration (300 μM) [1].
In vivo: AR-C 66096 behaved as a weak (pA50 3.68) but full P2x-purinoceptor agonist in preparations of the isolated rabbit ear artery and as a weak, competitive antagonist (apparent pKB 4.71) at P2Y-purinoceptors in the isolated guinea-pig aorta, indicating a selectivity of at least 9000 fold for the Pzrsubtype. In the latter preparation, non-specific relaxations were observed by concentrations of AR-C 66096 >10 μM [1].
Clinical trial: Up to now, AR-C 66096 is still in the preclinical development stage.
Reference:
[1] Humphries, R. G.; Tomlinson, W.; Ingall, A. H.; Cage, P. A.; Leff, P. FPL 66096: A Novel, Highly Potent and Selective Antagonist at Human Platelet P2T-purinoceptors. Br. J. Pharmacol. 1994, 113, 1057-1063.