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 IC50 values of 1.73nM and 2.91nM, respectively and SFLLR-induced guinea-pig and human platelet aggregation with the IC50 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 IC50 values of 93nM and 127nM, respectively or SFLLR-induced guinea-pig and human platelet aggregation with the IC50 values of 1.74μM and 2.36μM, 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 effects of ER121958 and SCH203099 on both SFLLR-induced platelet adhesion and aggregation were similar in both species.
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