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- W2046342446 abstract "The 5-lipoxygenase inhibitors WY-50,295 tromethamine, A-64,077, L-663,536 and ICI-207,968 were compared in a reverse passive Arthus reaction-induced pleurisy model of eicosanoid biosynthesis in the rat. When a 1 h pretreatment schedule was employed, all four inhibitors equivalently blocked leukotriene B4 (LTB4) production with ED50 values of 2.0-2.9 mg/kg p.o. Conversely, WY-50,295 tromethamine (225 mg/kg p.o.) and L-663,536 (100 mg/kg p.o.) did not significantly alter thromboxane B2 (TxB2) levels, whereas A-64,077 (50 mg/kg p.o.) and ICI-207,968 (100 mg/kg p.o.) significantly reduced TxB2 by 50 and 72%, respectively. When 3 and 18 h pretreatment schedules were employed, WY-50,295 tromethamine demonstrated a longer duration of action than the other 5-lipoxygenase inhibitors with ED50 values of 1.7 and 6.3 mg/kg p.o., respectively. At doses of 50 and 100 mg/kg p.o., all drugs tested significantly inhibited inflammatory cell influx by 15-27%, albeit in a non-dose-related manner. However, only A-64,077 significantly lowered fluid extravasation by 35%, presumably due to inhibition of cyclooxygenase product formation. These results demonstrate that in this rat reverse passive Arthus pleurisy model, WY-50,295 tromethamine potently and selectively inhibits 5-lipoxygenase in vivo, and possesses a longer duration of action than the other 5-lipoxygenase inhibitors employed." @default.
- W2046342446 created "2016-06-24" @default.
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- W2046342446 date "1991-01-01" @default.
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- W2046342446 title "Comparison of several new 5-lipoxygenase inhibitors in a rat Arthus pleurisy model" @default.
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- W2046342446 doi "https://doi.org/10.1016/0014-2999(91)90196-w" @default.
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