Thromboxane synthetase inhibition as antithrombotic strategy.
Journal: 1981/July - The Lancet
ISSN: 0140-6736
PUBMED: 6112447
Abstract:
The imidazole derivative UK-37 248, a thromboxane synthetase inhibitor, reduces the in-vitro formation of thromboxane B2 and hydroxyheptadecatrienoic acid by washed platelets, and this is compensated for by an increased production of prostaglandins E2 and F2 alpha; arachidonic acid challenged platelets pretreated with UK-37 248 also stimulate the production of prostacyclin by aspirin pretreated cultured endothelial cells. In a double-blind placebo controlled study to examine the in vivo properties of UK-37 248, human volunteers ingested 200 mg of the compound. Their serum thromboxane B2 levels dropped and their plasma 6-keto-prostaglandin F1 alpha values rose. Arachidonic acid induced platelet aggregation was completely inhibited whereas that elicited by adenosine-5'-diphosphate was unaffected. By reducing formation of pro-aggregatory tromboxane A2 and increasing production of anti-aggregatory prostacyclin, thromboxane synthetase inhibitors may be better than aspirin as antithrombotic agents.
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