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P2Y purinoceptor 12 Gαi Adenylate Cyclase Plasma membrane Ca-ADPase Cytochrome P450 1A2 Cytochrome P450 2B6 Cytochrome P450 2C19 Cytochrome P450 2D6 Cytochrome P450 3A4 Cytochrome P450 2C19 Cytochrome P450 3A4 Cytochrome P450 1A2 Cytochrome P450 2B6 Cytochrome P450 2D6 ADP cAMP UR-4501 Ca+ Ca+ Ticlopidine Ticlopidine Ticlopidine UR-4501 H+ O2 NADPH 2-Oxoticlopidine NADP H2O Magnesium cAMP The active metabolite of ticlopidine has high affinity for the P2Y12 receptor to which it binds reversibly, preventing binding of ADP. Gi protein no longer inhibits adenylate cyclase, leading to a buildup of cAMP activating calcium efflux pump and prevents platelet activation Normally, ADP binds to P2Y12, activating the coupled Gi protein, inhibiting adenylate cyclase and leading to a shortage of cAMP. Calcium efflux is inactivated by lack of cAMP, inducing platelet activation and aggregation. Platelet Extracellular Space Affected Organs Symptom Relief Blood Clot Blood Vessel or Cell Damage Ticlopidine is administered orally, through first pass metabolism into active metabolites Blood Vessel Endoplasmic Reticulum Ticlopidine is a prodrug and through first pass metabolism, it is converted to its active form. The active metabolite then travels through the bloodstream to act on P2Y receptor Hepatocyte
Melanosome Chloroplast Chloroplast Endoplasmic Reticulum P2RY12 GNAI1 ADCY10 Unknown CYP1A2 CYP2B6 CYP2C19 CYP2D6 CYP3A4 CYP2C19 CYP3A4 CYP1A2 CYP2B6 CYP2D6 Adenosine diphosphate cAMP UR-4501 Calcium Calcium Ticlopidine Ticlopidine Ticlopidine UR-4501 Hydrogen Ion Oxygen NADPH 2- Oxoticlopidine NADP Water
P2RY12 GNAI1 ADCY10 CYP1A2 CYP2B6 CYP2C19 CYP2D6 CYP3A4 CYP2C19 CYP3A4 CYP1A2 CYP2B6 CYP2D6 ADP cAMP UR-4501 Ca+ Ca+ Ticlopi Ticlopi Ticlopi UR-4501 H+ O2 NADPH 2O NADP H2O Mg2+ cAMP The active metabolite of ticlopidine has high affinity for the P2Y12 receptor to which it binds reversibly, preventing binding of ADP. Gi protein no longer inhibits adenylate cyclase, leading to a buildup of cAMP activating calcium efflux pump and prevents platelet activation Normally, ADP binds to P2Y12, activating the coupled Gi protein, inhibiting adenylate cyclase and leading to a shortage of cAMP. Calcium efflux is inactivated by lack of cAMP, inducing platelet activation and aggregation. Platelet Extracellular Space Affected Organs Symptom Relief Blood Clot Blood Vessel or Cell Damage Ticlopidine is administered orally, through first pass metabolism into active metabolites Blood Vessel Endoplasmic Reticulum Ticlopidine is a prodrug and through first pass metabolism, it is converted to its active form. The active metabolite then travels through the bloodstream to act on P2Y receptor Hepatocyte