Ticagrelor

Ticagrelor (AZD6140) is a reversible oral P2Y12 receptor antagonist for the treatment of platelet aggregation. In Vitro: Ticagrelor promotes a greater inhibition of adenosine 5′-diphosphate (ADP)–induced Ca²⁺ release in ished platelets vs other P2Y12R antagonists. This additional effect of ticagrelor beyond P2Y12R antagonism is in part as a consequence of ticagrelor inhibiting the equilibrative nucleoside transporter 1 (ENT1) on platelets, leading to accumulation of extracellular adenosine and activation of Gs-coupled adenosine A2A receptors^[1]. B16-F10 cells exhibit decreased interaction with platelets from ticagrelor-treated mice compared to saline-treated mice^[2]. In Vivo: In B16-F10 melanoma intravenous and intrasplenic metastasis models, mice treated with a clinical dose of ticagrelor (10 mg/kg) exhibits marked reductions in lung (84%) and liver (86%) metastases. Furthermore, ticagrelor treatment improves survival compared to saline-treated animals. A similar effect is observed in a 4T1 breast cancer model, with reductions in lung (55%) and bone marrow (87%) metastases following ticagrelor treatment^[2]. Single oral administration of ticagrelor (1-10 mg/kg) causes dose-related inhibitory effect on platelet aggregation. 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^[3].