Protease-activated receptor 1 antagonists prevent platelet aggregation and adhesion without affecting thrombin time

European Journal of Pharmacology
Florence Nadal-WollboldBruno Le Grand

Abstract

The aim of this study was to investigate the in vitro antithrombotic effects of two PAR1 antagonists, ER121958 and SCH203099 on both SFLLR-induced platelet adhesion and aggregation and on the thrombin time in human and guinea-pig platelets. ER121958 inhibited SFLLR-induced guinea-pig and human platelet adhesion with the IC(50) values of 1.73nM and 2.91nM, respectively and SFLLR-induced guinea-pig and human platelet aggregation with the IC(50) values of 2.74nM and 11.9nM, respectively. Similarly, SCH203099 exhibited a non competitive profile of inhibition on both SFLLR-induced guinea-pig and human platelet adhesion with the IC(50) values of 93nM and 127nM, respectively or SFLLR-induced guinea-pig and human platelet aggregation with the IC(50) values of 1.74microM and 2.36microM, respectively. These two antagonists failed to prolong the thrombin time. Altogether, these results highlighted the potent anti-platelets properties of both ER121958 and SCH203099 in an in vitro model of aggregation as well as in a static model of adhesion without any effect on the last step of coagulation cascade. Moreover, this work emphasized that guinea-pig is a suitable animal model to study the role of PAR1 antagonists since the magnitude of the eff...Continue Reading

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Citations

Jan 21, 2011·American Journal of Therapeutics·Jaya Prakash SugunarajChandrasekar Palaniswamy
May 15, 2012·International Journal of Radiation Oncology, Biology, Physics·Junru WangMartin Hauer-Jensen
Oct 25, 2012·Thrombosis and Haemostasis·Hannah Lee, Justin R Hamilton
Mar 6, 2012·Cellular Signalling·Esther LopezPedro C Redondo
Feb 11, 2015·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Jin-Hong WangBai Kang
Mar 30, 2013·Stroke; a Journal of Cerebral Circulation·Junhao YanJohn H Zhang

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