Reorientation of prostaglandin endoperoxide metabolism by a thromboxane synthetase inhibitor: in vitro and clinical observations.
1 Work with dazoxiben in vitro and in vivo suggests that a diminished capacity of platelets to synthesize thromboxane A2 results in a reorientation of the metabolism of cyclic endoperoxides. 2 Platelets of patients with congenital thromboxane synthetase deficiency show the same phenomenon. 3 In the presence of endothelium or leukocytes which have prostacyclin synthetase capacity, significant amounts of prostacyclin can be generated if thromboxane synthesis is blocked. 4 The local generation of aggregation inhibiting prostaglandins in areas of vascular damage may be an interesting therapeutic concept. 5 Pilot clinical studies of thromboxane synthetase inhibitor dazoxiben (UK 37248) in a small number of patients with peripheral arterial disease did not reveal major or consistent haemodynamic changes. 6 Attention is directed towards optimizing pharmacologically the generation and efficacy of the inhibitory prostaglandins produced when thromboxane synthetase is inhibited.
D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D003327:Coronary Disease / Q000188:drug therapy; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D010974:Platelet Aggregation / Q000187:drug effects; D011449:Prostaglandin Endoperoxides / Q000378:metabolism*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D013997:Time Factors
D007093:Imidazoles; D011449:Prostaglandin Endoperoxides; C029166:dazoxiben; D000242:Cyclic AMP; D010088:Oxidoreductases; D013930:Thromboxane-A Synthase; D002118:Calcium