Irreversible P2Y12 antagonists work by forming what type of bond with the receptor?

Irreversible P2Y12 antagonists function by forming a covalent disulfide bond with the receptor. This specific type of bond is crucial because it leads to a permanent inactivation of the P2Y12 receptor, which is essential for platelet aggregation. By binding covalently, these drugs effectively prevent ADP from activating the receptor, thereby inhibiting the platelet activation process that is critical in thrombus formation.

The permanent nature of this interaction distinguishes irreversible antagonists from reversible ones; once the drug is bound, its effect lasts for the lifetime of the platelet, which is about 7-10 days, as new platelets must be produced to restore function. This mechanism explains the strong and sustained antiplatelet effect associated with drugs like clopidogrel and prasugrel.