Rabinovici R, Yue T L, Farhat M, Smith E F, Esser K M, Slivjak M, Feuerstein G
Department of Pharmacology, Smithkline Beecham Laboratories, King of Prussia, Pennsylvania.
J Pharmacol Exp Ther. 1990 Oct;255(1):256-63.
BN 50739, a new PAF receptor antagonist, was tested in vitro and in vivo for its capacity to block PAF, endotoxin and recombinant human tumor necrosis factor-alpha (rTNF)-mediated effects. In vitro, BN 50739 blocked PAF-induced platelet aggregation by 60 to 100% at 0.2-1 x 10(-7) M (P less than .002), respectively. In the conscious rat, pretreatment (30 min) with BN 50739 (n = 5-13) dose-dependently attenuated PAF-induced hypotension (-5 +/- 5 vs. - 43 +/- 2 mm Hg, P less than .01) and shortened the recovery time of mean arterial pressure (22 +/- 13 vs. 325 +/- 46 sec, P less than .01). BN 50739 (10 mg/kg i.p., n = 5-11) prevented endotoxin (14.4 mg/kg) induced-hemoconcentration (54 +/- 1 vs. 46 +/- 1%, P less than .01) and reduced 24-hr mortality (100 vs. 60%, P less than .05). Only partial protection was conveyed by BN 50739 against the hypotensive response to endotoxin (115 +/- 3 vs. 91 +/- 4 mm Hg, P less than .03). Also, BN 50739 attenuated the lipopolysaccharide-induced elevation of plasma thromboxane B2 (21.2 +/- 0.8 vs. 46.7 +/- 11.8 pg/100 microliters, P less than .01) and tumor necrosis factor-alpha (7523 +/- 3983 vs. 26,430 +/- 3541 U/ml, P less than .05), whereas leukopenia and thrombocytopenia remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
新型血小板活化因子（PAF）受体拮抗剂BN 50739在体外和体内均被测试其阻断PAF、内毒素和重组人肿瘤坏死因子-α（rTNF）介导效应的能力。在体外，BN 50739在0.2 - 1×10⁻⁷ M时分别将PAF诱导的血小板聚集阻断60%至100%（P＜0.002）。在清醒大鼠中，用BN 50739（n = 5 - 13）预处理（30分钟）剂量依赖性地减轻PAF诱导的低血压（-5±5对-43±2 mmHg，P＜0.01），并缩短平均动脉压的恢复时间（22±13对325±46秒，P＜0.01）。BN 50739（10 mg/kg腹腔注射，n = 5 - 11）可预防内毒素（14.4 mg/kg）诱导的血液浓缩（54±1对46±1%，P＜0.01）并降低24小时死亡率（100%对60%，P＜0.05）。BN 50739对内毒素引起的低血压反应仅有部分保护作用（115±3对91±4 mmHg，P＜0.03）。此外，BN 50739减轻了脂多糖诱导的血浆血栓素B2升高（21.2±0.8对46.7±11.8 pg/100微升，P＜0.01）和肿瘤坏死因子-α升高（7523±3983对26430±3541 U/ml，P＜0.05），而白细胞减少和血小板减少则保持不变。（摘要截短于250字）
