SMPDB

Pathway Description

Ticlopidine Metabolism Pathway

Homo sapiens

Drug Metabolism Pathway

Created: 2013-09-11

Last Updated: 2025-01-24

Ticlopidine, marketed as Ticlid, is an antiplatelet drug that targets the P2Y12 receptor of platelets. Ticlopidine is taken orally and is a prodrug that must be metabolically activated before it can be effective. It first enters the liver and enters the endoplasmic reticulum where it is metabolized to form the active metabolite. First, it is catalyzed by cytochromes P450 2C19, 2B6 and 1A2 into 2-oxoclopidogrel. Secondly, it is processed by cytochromes P450 2B6, 2C9, 2C19, 3A4, 3A5, and serum paraoxonase/arylesterase 1 into the active metabolite of clopidogrel. The active metabolite of clopidogrel then enters the blood stream, where it binds irreversibly to the P2Y purinoreceptor 12 on the surface of platelet cells, preventing ADP from binding to and activating it. Clopidogrel prevents the activation of the Gi protein associated with the P2Y12 receptor from inactivating adenylate cyclase in the platelet, leading to a buildup of cAMP. This cAMP then activates calcium efflux pumps, preventing calcium buildup in the platelet, which would cause activation, and later, aggregation.

References

Ticlopidine Pathway References

Jennings LK, Saucedo JF: Antiplatelet and anticoagulant agents: key differences in mechanisms of action, clinical application, and therapeutic benefit in patients with non-ST-segment-elevation acute coronary syndromes. Curr Opin Cardiol. 2008 Jul;23(4):302-8. doi: 10.1097/HCO.0b013e3283021ad9.

Pubmed: 18520712

Saltiel E, Ward A: Ticlopidine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in platelet-dependent disease states. Drugs. 1987 Aug;34(2):222-62.

Pubmed: 3304967

Hollopeter G, Jantzen HM, Vincent D, Li G, England L, Ramakrishnan V, Yang RB, Nurden P, Nurden A, Julius D, Conley PB: Identification of the platelet ADP receptor targeted by antithrombotic drugs. Nature. 2001 Jan 11;409(6817):202-7. doi: 10.1038/35051599.

Pubmed: 11196645

Zhang FL, Luo L, Gustafson E, Lachowicz J, Smith M, Qiao X, Liu YH, Chen G, Pramanik B, Laz TM, Palmer K, Bayne M, Monsma FJ Jr: ADP is the cognate ligand for the orphan G protein-coupled receptor SP1999. J Biol Chem. 2001 Mar 16;276(11):8608-15. doi: 10.1074/jbc.M009718200. Epub 2000 Dec 4.

Pubmed: 11104774

Takasaki J, Kamohara M, Saito T, Matsumoto M, Matsumoto S, Ohishi T, Soga T, Matsushime H, Furuichi K: Molecular cloning of the platelet P2T(AC) ADP receptor: pharmacological comparison with another ADP receptor, the P2Y(1) receptor. Mol Pharmacol. 2001 Sep;60(3):432-9.

Pubmed: 11502873

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Ticlopidine

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P2Y purinoceptor 12

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Ticlopidine

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P2Y purinoceptor 12

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