Effect of the thromboxane synthetase inhibitor UK-37,248 (dazoxiben) upon platelet aggregation, coronary artery thrombosis and vascular reactivity

WA Schumacher and BR Lucchesi

The effects of the thromboxane synthetase inhibitor dazoxiben on thrombus formation, platelet aggregation and vascular reactivity have been studied in open-chest anesthetized dogs. Dazoxiben at 4 mg/kg prolonged the time required for occlusive thrombi to form at sites of electrical injury to the left circumflex coronary artery by 3-fold and also decreased venous thromboxane B2 concentrations by 45% within 30 min. The progressive decline in flow observed during thrombogenesis was interrupted by rapid and spontaneous reactive hyperemic responses, the frequency and number of which were diminished by dazoxiben. In vitro platelet aggregation responses to ADP and collagen determined during the course of these experiments also were inhibited to a variable extent. The effect of dazoxiben on coronary vascular responsiveness was examined using an in situ constant pressure perfused coronary vascular bed. Although basal left circumflex coronary blood flow was unaffected by the drug, vasodilation induced by arachidonic acid, but not prostacyclin, was potentiated. The data suggest that dazoxiben possesses in vivo antithrombotic activity due to modification of platelet reactivity and that it can enhance coronary vasodilator responses to exogenously administered arachidonic acid.

Volume 227, Issue 3, pp. 790-796, 12/01/1983
Copyright © 1983 by American Society for Pharmacology and Experimental Therapeutics