page_title: Adenosine diphosphate receptor inhibitor
section_title: Mechanism of action
hierarchical_section_title: Adenosine diphosphate receptor inhibitor / Mechanism of action
caption_attribution_description: English: Graphical abstract of how P2Y12 antagonist inhibit platelet activation.
context_page_description: Adenosine diphosphate receptor inhibitors are a drug class of antiplatelet agents, used in the treatment of acute coronary syndrome or in preventive treatment for patients who are in risk of thromboembolism, myocardial infarction or a stroke. These drugs antagonize the P2Y₁₂ platelet receptors and therefore prevent the binding of ADP to the P2Y₁₂ receptor. This leads to a decrease in aggregation of platelets, prohibiting thrombus formation. The P2Y₁₂ receptor is a surface bound protein found on blood platelets. They belong to G protein-coupled purinergic receptors and are chemoreceptors for ADP.
  The first drug introduced in this class was ticlopidine but due to adverse effects it is not much used today. Ticlopidine, clopidogrel and prasugrel are all thienopyridines that cause irreversible inhibition of P2Y₁₂ receptor. They are all prodrugs which need to be converted to an active metabolite in-vivo to inhibit the P2Y₁₂ receptor. On the other hand, novel drugs like ticagrelor and cangrelor are non-thienopyridines and reversibly inhibit P2Y₁₂ meaning they act directly on the receptor without the requirement of metabolic activation and display faster onset and offset of action.
context_section_description: The molecular target of the active metabolite of ADP receptor inhibitors is the P2Y₁₂ receptor. P2Y₁₂ receptor is a G-coupled receptor and is activated by adenosine diphosphate. ADP binds to the P2Y₁₂ receptor that leads to inhibition of adenyl cyclase and thereby decreases the intracellular levels of cAMP. This reduction of cAMP reduces phosphorylation of vasodilator stimulated phosphoprotein that leads to the activation of the glycoprotein IIb/IIIa receptors.  Activation of the glycoprotein IIb/IIIa receptors increases thromboxane production and prolonged platelet aggregation. Ticlopidine, clopidogrel and prasugrel are thienopyridine prodrugs that are irreversible platelet inhibitors of the P2Y₁₂ receptor. Cangrelor and ticagrelor are direct –acting P2Y₁₂ inhibitors that change the conformation of the P2Y₁₂ receptor and therefore, results in reversible platelet inhibition of the receptor. Thienopyridines are metabolized in the liver and the intestinal to active metabolites.
caption: P2Y12 antagonists and how they bind to the receptor.
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