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- W2020163179 abstract "The effects of (E)-3-[p-(1H-imidazol-1-ylmethyl)phenyl]-2-propenoic acid (OKY-046) on thromboxane A2 (TXA2) synthetase in vitro and on experimental animal models of sudden death and cerebral infarction were studied. IC50 values of OKY-046 for the TXA2 synthetase of human, rabbit, dog and guinea pig washed platelets were 0.004. 0.004. 0.26 and 2.4 μM. respectively. OKY-046 at concentrations up to 1 mM. however, did not inhibit prostacyclin (PGI2) synthetase from bovine aorta microsomes or cyclooxygenase and PGE2 isomerase from sheep seminal vesicle microsomes. Similarly, platelet 12-lipoxygenase was not affected by OKY-046. Evidence for a re direction of arachidonate metabolism from thromboxane synthesis toward PGI2 synthesis was obtained using rat peritoneal cells. Namely. OKY-046 increased PGI2 production accompanied by an inhibition of TXA2 production at a concentration of more than 1 μM. OKY-046 at a dose of 0.1 mg/kg (i.v.) in dogs inhibited the aortic and mesenteric arterial contraction of rabbit induced by the addition of arachidonate to extracorporated blood of the dogs. OKY-046 at a dose of 0.3 mg/kg (i.v.) prevented the arachidonate-induced sudden death and also decreased (he incidence of cerebral infarction induced by injection of arachidonate into the internal carotid artery in rabbits. Aspirin also decreased the incidence of cerebral infarction at a dose of 30 mg/kg (i.V.). These results suggest that OKY-046 may be valuable for the treatment of cerebrovascular and cardiovascular diseases associated with vasoconstriction and thrombosis due to TXA2." @default.
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- W2020163179 date "1986-01-01" @default.
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- W2020163179 title "Pharmacological Studies on the TXA2 Synthetase Inhibitor (E)-3-[p(1H-lmidazol-1-Ylmethyl)Phenyl]-2-Propenoic Acid (OKY-046)" @default.
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- W2020163179 doi "https://doi.org/10.1254/jjp.41.393" @default.
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