Blockade of platelet adenosine 5′-diphosphate (ADP) receptors has been established as a key therapeutic strategy in cardiovascular disease. Among the thienopyridines, Clopidogrel decreases ischemic outcomes in patients who present with acute coronary syndromes (ACS). The more potent Prasugrel has been demonstrated to be superior to Clopidogrel in patients with ACS who are scheduled to undergo percutaneous coronary intervention.

Unlike the thienopyridines, which are irreversible agents, Ticagrelor is a reversible ADP receptor antagonist. Ticagrelor binds reversibly and directly to ADP P2Y12 receptors on platelets, which changes the conformation of these receptors. Such binding inhibits platelet activation and eventual aggregation.

Ticagrelor is a reversible oral P2Y12 receptor antagonist for the treatment of platelet aggregation.

Firstly, Ticagrelor (AZD6140) promotes a greater inhibition of ADP–induced Ca2+ release in ished platelets vs other P2Y12R antagonists. Secondly, Ticagrelor inhibiting the equilibrative nucleoside transporter 1 (ENT1) on platelets. It leads accumulation of extracellular adenosine and activation of Gs-coupled adenosine A2A receptors. Moreover, B16-F10 cells exhibit decreased interaction with platelets from ticagrelor-treated mice compared to saline-treated mice.

In B16-F10 melanoma intravenous and intrasplenic metastasis models, Ticagrelor (10 mg/kg) exhibits marked reductions in lung (84%) and liver (86%) metastases. Furthermore, it improves survival compared to saline-treated animals. Meanwhile, in a 4T1 breast cancer model, Ticagrelor reduces lung (55%) and bone marrow (87%) metastases. Ticagrelor (single, oral, 1-10 mg/kg) causes dose-related inhibitory effect on platelet aggregation. In addition, Ticagrelor, at the highest dose (10 mg/kg) significantly inhibits platelet aggregation at 1 h after dosing. And the peak inhibition is observed at 4 h after dosing.

To sumup, Ticagrelor is a reversible oral P2Y12 receptor antagonist for the treatment of platelet aggregation.

References:

[1] Bhatt DL. Nat Rev Cardiol. 2009 Dec;6(12):737-8.

[2] Gebremeskel S, et al. Int J Cancer. 2015 Jan 1;136(1):234-40.

[3] Sugidachi A, et al. Br J Pharmacol. 2013 May;169(1):82-9.

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