Thromb Haemost 1987; 58(03): 827-830
DOI: 10.1055/s-0038-1645998
Original Article
Schattauer GmbH Stuttgart

On the Mechanism of Thrombolytic Action of Thromboxane Synthetase Inhibitors

R Korbut
The Department of Pharmacology, N. Copernicus Academy of Medicine, Cracow, Poland
,
A Dembińska-Kieć
The Department of Pharmacology, N. Copernicus Academy of Medicine, Cracow, Poland
,
J Świȩs
The Department of Pharmacology, N. Copernicus Academy of Medicine, Cracow, Poland
,
A Źmuda
The Department of Pharmacology, N. Copernicus Academy of Medicine, Cracow, Poland
,
R J Gryglewski
The Department of Pharmacology, N. Copernicus Academy of Medicine, Cracow, Poland
› Author Affiliations
Further Information

Publication History

Received 12 January 1987

Accepted after revision 12 May 1987

Publication Date:
28 June 2018 (online)

Preview

Summary

Using our in vivo model for studying drugs which prevent deposition of thrombi or dissipate thrombi formed in extracorporeal circulation over a collagen strip superfused with arterial blood of anaesthetized and heparinized cats, we have found that dazoxiben - a thromboxane synthetase inhibitor - possesses not only antithrombotic but also thrombolytic potency in vivo (ED50 = 3.8 mg/kg i.v.). The thrombolytic potency of dazoxiben was antagonized by aspirin at a dose of 50 mg/kg i.v. Moreover, dazoxiben stimulated the generation of prostacyclin in isolated rat aortic slices incubated in platelet rich plasma, but not in platelet poor plasma. It is suggested that the thrombolytic potency of thromboxane synthetase inhibitors after their systemic administration is associated with the release of prostacyclin and/or prostacyclin-stable metabolites by the vascular endothelium owing to feeding of prostacyclin synthetase with prostaglandin endoperoxides acumulated in platelets following the inhibition of thromboxane synthetase.