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P2Y purinoceptor 12 Gαi Adenylate cyclase type 10 Plasma membrane Ca-ADPase Cytochrome P450 1A2 Cytochrome P450 2B6 Cytochrome P450 2C19 Cytochrome P450 2B6 Cytochrome P450 2C19 Cytochrome P450 2C9 Cytochrome P450 3A4 Cytochrome P450 3A5 Serum paraoxonase/arylesterase 1 ADP cAMP Active Metabolite of Clopidogrel Clopidogrel Ca+ Ca+ O2 H2O 2-Oxoclopidogrel H2O2 Magnesium cAMP Heme Heme Heme Heme Heme Heme Heme Heme Calcium Blood Vessel or Cell Damage Oral Administration Clopidogrel binds irreversibly to the P2Y12 receptor of platelets, preventing binding of ADP. Normally, ADP binds to P2Y12, activating the coupled Gi protein, inhibiting adenylate cyclase and leading to a shortage of cAMP. Clopidogrel prevents the Gi protein from inactivating adenylate cyclase in the cell, leading to a buildup of cAMP, which activates the calcium efflux pump and prevents platelet activation. Calcium efflux is inactivated by lack of cAMP, inducing platelet activation and aggregation. Platelet Cytosol Extracellular Space Affected Organs Symptom Relief Blood Clot Endoplasmic Reticulum Cytosol
Chloroplast Chloroplast Endoplasmic Reticulum P2RY12 GNAI1 ADCY10 Unknown CYP1A2 CYP2B6 CYP2C19 CYP2B6 CYP2C19 CYP2C9 CYP3A4 CYP3A5 PON1 Adenosine diphosphate cAMP Active Metabolite of Clopidogrel Clopidogrel Calcium Calcium Oxygen Water 2-Oxoclopidogrel Hydrogen peroxide Blood Vessel or Cell Damage Oral Administration