Clopidogrel is an antiplatelet agent; what is its mechanism?

• A. P2Y12 receptor antagonist, inhibits ADP-mediated platelet aggregation.
• B. P2Y12 receptor agonist.
• C. Cyclooxygenase-1 (COX-1) inhibitor.
• D. Direct thrombin inhibitor.

Answer: (A)

Clopidogrel works by blocking the P2Y12 receptor on platelets, which stops ADP from signaling platelets to activate and aggregate. It’s a prodrug that the liver metabolizes (primarily by CYP enzymes) into an active compound that irreversibly binds the P2Y12 receptor. Because the binding is permanent for the life of the platelet, the platelet cannot participate in aggregation until new platelets are made, giving a lasting antiplatelet effect. This mechanism is different from aspirin, which inhibits COX-1, and from direct thrombin inhibitors.