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Figure 1 Mechanism of action of clopidogrel. Clopidogrel competitively and irreversibly inhibits the adenosine diphosphate (ADP) P2Y12 receptor; ADP binds to the P2Y1 receptor to induce change in platelet shape and a weak and transient platelet aggregation. The binding of ADP to its Gi-coupled P2Y12 receptor liberates the Gi protein subunits {alpha}Gi and ß{gamma}. The subunit {alpha}Gi leads to the inhibition of adenylyl cyclase (AC), which, in turn, lowers the cyclic adenosine monophosphate (cAMP) level. This inhibits the cAMP-mediated phosphorylation of vasodilator-stimulated phosphoprotein (VASP) (VASP-P), which is known to be closely related to the inhibition of glyprotein IIb/IIIa receptor activation. The subunit ß{gamma} activates the phosphatidylinositol 3-kinase (PI3K), which potentiates dense- and {alpha}-granule secretion. Multiple arrows within a given pathway indicate that intermediate steps may be involved. Dotted arrows indicate inhibition, whereas solid arrows represent activation. CYP450 = cytochrome P450; PGE1 = prostaglandin E1; PKA = protein kinase activation; PLC = phospholipase C.





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