P2Y12 receptors: structure and function

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