Acute arterial thrombosis in rabbits: reduced platelet accumulation after treatment with thromboxane synthetase inhibitor dazoxiben hydrochloride, (UK-37, 248-01).
Acute thrombosis was induced in the carotid arteries of anaesthetised rabbits by local electrical stimulation (1mA for 2 min) of the vessel wall. Histological findings confirmed the platelet-rich composition of the thrombus. Platelet accumulation at the stimulus site was quantitated with "'Indium-labelling of autologous platelets. In rabbits injected intravenously with either 2 mg/kg dazoxiben or 10 mg/kg aspirin, accumulation of labelled platelets was considerably reduced. Animals which received vehicle injection only, showed no such reduced thrombus formation. In separate experiments in anaesthetised rabbits, the levels of TxB2 and 6KPGF1 alpha in clotting blood were measured in blood samples taken from animals which had received the above drug treatments. Aspirin markedly reduced the production of both arachidonate metabolites. In contrast, dazoxiben almost totally inhibited TxB2 production but caused a 3.5 fold increase in the levels of 6KPGF1 alpha. These findings demonstrate an anti-thrombotic effect and confirm the mechanistic selectivity of a thromboxane synthetase inhibitor.
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000208:Acute Disease; D000818:Animals; D001241:Aspirin / Q000627:therapeutic use; D002341:Carotid Artery Thrombosis / Q000188:drug therapy*; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D007093:Imidazoles / Q000627:therapeutic use*; D066298:In Vitro Techniques; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D010974:Platelet Aggregation / Q000187:drug effects*; D011817:Rabbits; D013929:Thromboxane B2 / Q000037:antagonists & inhibitors / Q000097:blood; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D005343:Fibrinolytic Agents; D007093:Imidazoles; C029166:dazoxiben; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D010088:Oxidoreductases; D013930:Thromboxane-A Synthase; D001241:Aspirin