新型血小板活化因子拮抗剂BN 50739的体外和体内药理学特性

Pharmacologic profile of BN 50739, a new PAF antagonist in vitro and in vivo.

作者信息

Yue T L, Rabinovici R, Farhat M, Feuerstein G

机构信息

Department of Pharmacology, SmithKline Beecham, King of Prussia, PA 19406-0939.

出版信息

Prostaglandins. 1990 May;39(5):469-80. doi: 10.1016/0090-6980(90)90031-p.

DOI:10.1016/0090-6980(90)90031-p

PMID:2353116

Abstract

The effect of a new PAF antagonist BN 50739 was studied on PAF-induced [3H]-serotonin release from washed rabbit platelets in vitro and on PAF-induced hypotension in vivo. BN 50739 competitively inhibited PAF-induced [3H]-serotonin release from the platelets in a dose-dependent manner. In the presence of 4, 10 and 50 nM of BN 50739, the concentration of PAF inducing 50% maximal [3H]-serotonin release from the platelets (EC50) increased from 2.15 nM to 5.10, 45.10 and 900 nM, respectively. The IC50 of BN 50739 for PAF (10 nM) induced [3H]-serotonin release was 3.67 nM. Under the same experimental condition, the IC50s of BN 50726, BN 50730, BN 50741, WEB 2086, SRI 63-441 and BN 52021 were 5.40, 4.61, 6.88, 5.98, 40.90 nM and 14.90 microM, respectively. PAF-induced hypotension in conscious rats was also inhibited dose-dependently by i.p. pretreatment of BN 50739 (3 and 10 mg/kg). PAF-induced hypotension was diminished both in magnitude and duration in rats pretreated with BN 50739. These data taken together indicate that BN 50739 is a most potent PAF antagonist in vitro and in vivo.

摘要

研究了新型血小板活化因子（PAF）拮抗剂BN 50739对体外PAF诱导的洗涤兔血小板[3H] - 5 - 羟色胺释放以及体内PAF诱导的低血压的影响。BN 50739以剂量依赖性方式竞争性抑制PAF诱导的血小板[3H] - 5 - 羟色胺释放。在存在4、10和50 nM的BN 50739时，诱导血小板50%最大[3H] - 5 - 羟色胺释放的PAF浓度（EC50）分别从2.15 nM增加到5.10、45.10和900 nM。BN 50739对PAF（10 nM）诱导的[3H] - 5 - 羟色胺释放的IC50为3.67 nM。在相同实验条件下，BN 50726、BN 50730、BN 50741、WEB 2086、SRI 63 - 441和BN 52021的IC50分别为5.40、4.61、6.88、5.98、40.90 nM和14.90 μM。腹腔注射预处理BN 50739（3和10 mg/kg）也能剂量依赖性地抑制清醒大鼠中PAF诱导的低血压。用BN 50739预处理的大鼠中，PAF诱导的低血压在幅度和持续时间上均有所减轻。这些数据综合表明，BN 50739在体外和体内都是一种非常有效的PAF拮抗剂。