Thromb Haemost 2003; 90(03): 406-413
DOI: 10.1160/TH03-02-0115
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Antithrombotic and thrombolytic efficacy of YM-254890, a Gq/11 inhibitor, in a rat model of arterial thrombosis

Tomihisa Kawasaki
1   Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Tsukuba, Ibaraki, Japan
,
Masatoshi Taniguchi
2   Chemistry Laboratories Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Tsukuba, Ibaraki, Japan
,
Yumiko Moritani
1   Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Tsukuba, Ibaraki, Japan
,
Kazumi Hayashi
1   Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Tsukuba, Ibaraki, Japan
,
Tetsu Saito
3   Molecular Medicine Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Tsukuba, Ibaraki, Japan
,
Jun Takasaki
3   Molecular Medicine Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Tsukuba, Ibaraki, Japan
,
Koji Nagai
4   Microbiology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Itabashi, Tokyo, Japan
,
Osamu Inagaki
1   Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Tsukuba, Ibaraki, Japan
,
Hisataka Shikama
1   Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Tsukuba, Ibaraki, Japan
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Publikationsverlauf

Received 25. Februar 2003

Accepted after revision 28. Mai 2003

Publikationsdatum:
05. Dezember 2017 (online)

Summary

We examined the antithrombotic and thrombolytic effects of the Gq/11 inhibitor YM-254890 in an electrically-induced carotid artery thrombosis model in rats. YM-254890 dose-dependently inhibited ex vivo ADP-induced platelet aggregation after i.v. bolus injection. In the thrombosis study, YM-254890 dose-dependently prolonged time to occlusion at doses of 3 and 10 μg/kg i.v. and decreased occlusion rate at 10 μg/kg i.v. In the thrombolysis study, YM-254890 at 30 μg/kg i.v. shortened the time to reperfusion and prevented reocclusion after thrombolysis with a modified tissue-type plasminogen activator. YM-254890, at 10 μg/kg and more, significantly improved carotid patency status after thrombolysis. However, at 30 μg/kg and more, YM-254890 decreased systemic blood pressure. These results suggest that YM-254890 may be effective for treating Gq-mediated diseases, and that YM-254890 is a useful tool for investigating the biological roles of Gq/11.

 
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