P2Y12 receptors: structure and function

The platelet P2Y(12) receptor (P2Y(12)R) for adenosine 5diphosphate (ADP) plays a central role in platelet function, hemostasis, and thrombosis. Patients with inherited P2Y(12)R defects display mild-to-moderate bleeding diatheses. Defects of P2Y(12)R should be suspected when ADP, even at high concentrations (10m), is unable to induce full, irreversible platelet aggregation. P2Y(12)R also plays a role in inflammation: its role in the pathogenesis of allergic asthma has been well characterized. In addition, inhibition or genetic deficiency of P2Y(12)R has antitumor effects. Drugs inhibiting P2Y(12)R are potent antithrombotic drugs. Clopidogrel is the P2Y(12)R antagonist that is most widely used in the clinical setting. Its most important drawback is its inability to inhibit adequately P2Y(12)R-dependent platelet function in about one-third of patients. New drugs, such as prasugrel and ticagrelor, which effectively inhibit P2Y(12)R in the vast majority of patients, have proved to be more efficacious than clopdidogrel in preventing major adverse cardiovascular events.