Effect of Bay U 3405, a new thromboxane antagonist, on collagen-induced thromboembolism in rabbits.
Bay U 3405 [(3R)-3-(4-fluorophenylsulfonamido)-1,2,3,4-tetrahydro-9- carbazolepropanoic acid] potently inhibits platelet aggregation, thromboxane A2-induced contraction of smooth muscles, and coronary artery thrombosis. We have previously demonstrated inhibition of arachidonic acid-induced sudden death by Bay U 3405. The purpose of this study was to investigate the effects of Bay U 3405 on thromboembolism provoked by collagen. Collagen fibrils dissolved in an isotonic glucose solution were injected into a marginal ear vein of anesthetized rabbits. Sudden death occurred within a few minutes due to elevated thromboxane A2 levels causing intravascular platelet aggregation and myocardial ischemia. In the vehicle-treated group, 100% of the animals died. One of the most prominent parameters was the massive fall in blood pressure. All animals pretreated with 10 mg/kg orally Bay U 3405 survived, showing only a transient hypotensive effect. Tracings of the electrocardiogram and heart rate were unchanged. Bay U 3405 will therefore be useful to elucidate the role of thromboxane A2 in various cardiovascular and respiratory diseases.
Seuter
F
F
Institute of Pharmacology, Bayer AG, Wuppertal, FRG.
Perzborn
E
E
Fiedler
V B
VB
D000818:Animals; D001794:Blood Pressure; D002227:Carbazoles / Q000627:therapeutic use*; D003094:Collagen; D004562:Electrocardiography; D006339:Heart Rate; D008297:Male; D011817:Rabbits; D013449:Sulfonamides / Q000627:therapeutic use*; D013923:Thromboembolism / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D013931:Thromboxanes / Q000037:antagonists & inhibitors*
D002227:Carbazoles; D013449:Sulfonamides; D013931:Thromboxanes; D003094:Collagen; C063119:ramatroban