Protease-activated receptor 1 antagonists prevent platelet aggregation and adhesion without affecting thrombin time.
Eur J Pharmacol
; 644(1-3): 188-94, 2010 Oct 10.
Article
em En
| MEDLINE
| ID: mdl-20655904
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 effects of ER121958 and SCH203099 on both SFLLR-induced platelet adhesion and aggregation were similar in both species.
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Base de dados:
MEDLINE
Assunto principal:
Pirróis
/
Quinazolinas
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Inibidores da Agregação Plaquetária
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Receptor PAR-1
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Isoindóis
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article