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.
|
Authors | J W Berkenkopf, B M Weichman |
Journal | European journal of pharmacology
(Eur J Pharmacol)
Vol. 193
Issue 1
Pg. 29-34
(Jan 25 1991)
ISSN: 0014-2999 [Print] Netherlands |
PMID | 1646730
(Publication Type: Comparative Study, Journal Article)
|
Chemical References |
- Biomarkers
- Eicosanoids
- Lipoxygenase Inhibitors
- Leukotriene B4
|
Topics |
- Animals
- Arthus Reaction
(drug therapy, metabolism)
- Biomarkers
- Dose-Response Relationship, Drug
- Eicosanoids
(metabolism)
- Exudates and Transudates
(metabolism)
- Inflammation
(metabolism, physiopathology)
- Leukotriene B4
(biosynthesis)
- Lipoxygenase Inhibitors
- Male
- Pleurisy
(drug therapy, metabolism)
- Radioimmunoassay
- Rats
|