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.
Keywords
Dazoxiben - Inhibitors of thromboxane synthetase - Thrombolysis - Prostaglandin endoperoxides
