P2Y12 receptor antagonists: a rapidly expanding group of antiplatelet agentsThe opinions expressed in this article are not necessarily those of the Editors of the European Heart Journal or of the European Society of Cardiology.

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Abstract
Adenosine-5′-diphosphate (ADP) plays a key role in platelet function, because, although ADP itself is a weak platelet agonist, when secreted from the platelet dense granules where it is stored, it amplifies the platelet responses induced by other platelet agonists.1 The transduction of the ADP signal involves both a transient rise in free cytoplasmic calcium mediated by the Gq-coupled P2Y1 receptor, and inhibition of adenylyl cyclase mediated by the Gi-coupled P2Y12 receptor. Concomitant activation of both the Gq and Gi pathways by ADP is necessary to elicit normal ADP-induced platelet aggregation. Activation of the Gq pathway through P2Y1 leads to platelet shape change and rapidly reversible aggregation, whereas the activation of the Gi pathway through P2Y12 elicits a slow progressive and sustained platelet aggregation not preceded by shape change. In addition to its role in ADP-induced platelet aggregation, P2Y12 mediates the potentiation of platelet secretion induced by strong agonists and the stabilization of thrombin-induced platelet aggregates.1 P2Y12 has a more selective tissue distribution than P2Y1, making it an attractive molecular target for therapeutic intervention. Indeed, P2Y12 is the target of efficacious antithrombotic agents like ticlopidine and clopidogrel, which are already used in clinical practice either alone or in combination with other antithrombotic drugs.2