New P2Y 12 Inhibitors

Abstract

A denosine diphosphate (ADP) plays a key role in the genesis of physiological platelet-rich hemostatic plugs and of pathological arterial thrombi. 1 The transduction of the ADP signal involves its interaction with 2 platelet receptors, the G q -coupled P2Y 1 receptor and the G i -coupled P2Y 12 receptor, which belong to the family of purinergic P2 receptors.Concomitant activation of both the G q and G i pathways by ADP is necessary to elicit normal platelet aggregation.2 In addition to its role in ADP-induced platelet aggregation, P2Y 12 (Figure 1) also mediates the potentiation of platelet secretion induced by strong agonists, which is independent of the formation of large aggregates and thromboxane A 2 synthesis 2 ; the stabilization of thrombin-induced platelet aggregates 2 ; shear-induced platelet aggregation 2 ; and the inhibition of the antiplatelet effects of the natural regulator of platelet function, prostacyclin.3 In contrast to P2Y 1 , P2Y 12 has a very selective tissue distribution, making it an attractive molecular target for therapeutic intervention.Indeed, P2Y 12 is the target of efficacious antithrombotic agents.