替格瑞洛对腺苷的影响及其生物学效应研究进展

Research progress in the effects of ticagrelor on adenosine and its biological effects

替格瑞洛是一种新型的P2Y12受体拮抗剂,可与血小板P2Y12受体可逆结合,主要经细胞色素P450酶3A4(CYP3A4)代谢,口服后可迅速产生血小板抑制作用,是治疗急性冠状动脉综合征(ACS)的重要药物之一。与其他噻吩吡啶类(氯吡格雷、普拉格雷)抗血小板药物临床获益不同之处在于,替格瑞洛的某些临床特征独立于P2Y12受体拮抗作用。替格瑞洛还可抑制平衡核苷转运体1(ENT1),从而抑制细胞内腺苷摄取,增加腺苷半衰期及血浆腺苷浓度水平,发挥保护心肌细胞、增加冠状动脉灌注血流、抑制血小板聚集等等作用。随着腺苷浓度的升高,也会引起一些如呼吸困难、肌酐和尿酸水平的升高、心动过缓等不良反应。本文将对替格瑞洛对腺苷的影响及其所产生的生物学效应的研究进展进行综述。

As a new type of P2Y12 receptor antagonist,Ticagrelor can reverently bind to platelet P2Y12 receptor.It is mainly metabolized by cytochrome P450 enzyme 3A4(CYP3A4)and can produce rapid platelet inhibition after oral administration.It is one of the important treatment drugs of acute coronary syndrome.Different from other thiophene pyridines antiplatelet drugs(clopidogrel,Prasugrel),some clinical features of Ticagrelor are independent of P2Y12 receptor antagonism.Ticagrelor can also inhibit the equilibrative nucleoside transporter 1(ENT1),thereby inhibiting the uptake of adenosine in cells,increasing the half-life period and concentration level of adenosine in plasma,which protects cardiomyocytes,increases coronary artery perfusion blood flow and inhibits platelet aggregation.As adenosine concentration increases,some adverse reactions such as dyspnea,elevated creatinine,increased uric acid levels,and bradycardia can also be increased.The effects of Ticagrelor on adenosine and its biological effects will be reviewed in this article.