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- W2992745812 abstract "UK-37,248, 4-(2-(lH-imidazol-l-yl)ethoxy)benzoic acid hydrochloride, potently inhibited human blood platelet microsomal thronfooxane (Tx) synthetase, IC50=3xl0-9M. TxB2 was quantitated by a specific radioimmunoassay (RIA). In contrast (PG) endoperoxide synthesis by ram seminal vesicle microsomes and prostacylclin (PGI2) synthesis by pig aortic microsomes/were minimally affected by concentrations of UK-37,248 up to 1x10-4M. In the rabbit isolated perfused lung arachidonic acid (AA) metabolites were quantitated by differential bioassay. Concentrations of UK-37,248 from 10-7-10-6M selectively reduced TxA2 production from AA but increased the release of PGI2 and other PGs. The effect of UK-37,248 in the whole animal was studied by estimating TxB2 levels in blood samples removed before and after dosing. The samples were allowed to clot and the serum TxB2 levels were assessed by RIA. In anaesthetised rabbits, 15 minutes after injection of 0.3mg/kg i.v. UK-37,248, serum TxB2 levels were reduced by 75%. In dogs the compound was similarly effective, lmg/kg p.o. inhibiting TxB2 production by 79% two hours after dosing. Aggregation of human platelet-rich plasma in vitro, initiated by threshold collagen, was inhibited by UK-37,248 (IC50=4.8x10-6M). In rabbits, UK-37,248 at 2mg/kg i.v. prevented the mortality due to pulmonary embolism and reduced the associated thrombocytopenia and elevation of plasma TxB2 caused by i.v. AA. In conclusion, UK-37,248 is a selective inhibitor of platelet Tx-synthetase with antiaggregatory and anti-thrombotic activity." @default.
- W2992745812 created "2019-12-13" @default.
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- W2992745812 date "1981-01-01" @default.
- W2992745812 modified "2023-09-24" @default.
- W2992745812 title "UK-37,248, A Novel, Selective Thromboxane Synthetase Inhibitor With Anti-Aggregatory And Anti-Thrombotic Activity" @default.
- W2992745812 doi "https://doi.org/10.1055/s-0038-1652828" @default.
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