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

Abstract

We examined the antithrombotic and thrombolytic effects of the G(q/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 dosedependently prolonged time to occlusion at doses of 3 and 10 g/kg i.v. and decreased occlusion rate at 10 g/kg i.v. In the thrombolysis study, YM-254890 at 30 micro g/kg i.v. shortened the time to reperfusion and prevented reocclusion after thrombolysis with a modified tissue-type plasminogen activator. YM-254890, at 10 micro g/kg and more, significantly improved carotid patency status after thrombolysis. However, at 30 micro g/kg and more, YM-254890 decreased systemic blood pressure. These results suggest that YM-254890 may be effective for treating G(q)-mediated diseases, and that YM-254890 is a useful tool for investigating the biological roles of G(q/11).

• Authors: Tomihisa Kawasaki, Masatoshi Taniguchi, Yumiko Moritani, Kazumi Hayashi, Tetsu Saito, Jun Takasaki, Koji Nagai, Osamu Inagaki, Hisataka Shikama
• Journal: Thrombosis and haemostasis (Thromb Haemost) Vol. 90 Issue 3 Pg. 406-13 (Sep 2003) ISSN: 0340-6245 [Print] Germany
• PMID: 12958608 (Publication Type: Journal Article)

Chemical References

• Fibrinolytic Agents
• Peptides, Cyclic
• YM-254890
• Tissue Plasminogen Activator
• GTP-Binding Protein alpha Subunits, Gq-G11

Topics

• Animals
• Blood Pressure (drug effects)
• Carotid Artery Diseases (drug therapy, prevention & control)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Drug Evaluation, Preclinical
• Drug Therapy, Combination
• Fibrinolytic Agents (administration & dosage, pharmacology)
• GTP-Binding Protein alpha Subunits, Gq-G11 (antagonists & inhibitors)
• Peptides, Cyclic (administration & dosage, therapeutic use)
• Platelet Aggregation (drug effects)
• Rats
• Thrombolytic Therapy (methods)
• Thrombosis (drug therapy, prevention & control)
• Tissue Plasminogen Activator (pharmacology)
• Treatment Outcome
• Vascular Patency (drug effects)