Sakuma Y, Shirato M, Nagaoka J, Obaishi H, Tsunoda H, Katayama S, Ono H, Katayama K
Tsukuba Research Laboratories, Eisai Co., Ltd., Ibaraki, Japan.
Arzneimittelforschung. 1991 Dec;41(12):1255-9.
The effects of a newly synthesized platelet-activating factor (PAF) antagonist, (S)-(+)-6-(2-chlorophenyl)-3-cyclopropanecarbonyl-8,11- dimethyl-2,3,4,5-tetrahydro-8H-pyrido[4',3':4,5]thieno[3,2-f] [1,2,4]triazolo[4,3-a][1,4]diazepine (E-6123, CAS 131614-02-3) on microvascular permeability, systemic hypotension and nephrosis were investigated. E-6123 inhibited PAF injection-induced microvascular permeability (edema) in guinea pigs after oral administration at 3 micrograms/kg. The inhibitory effects of E-6123 were very potent compared to those of other PAF antagonists. E-6123 reversed PAF and/or endotoxin injection-induced hypotension in rats after intravenous administration at 3 micrograms/kg. The increase in urinary protein excretion of rats in which nephrosis had been induced by intraperitoneal injection of aminonucleoside was not inhibited by oral administration of E-6123 at 10 mg/kg/d.
研究了一种新合成的血小板活化因子（PAF）拮抗剂，（S）-（+）-6-（2-氯苯基）-3-环丙烷羰基-8,11-二甲基-2,3,4,5-四氢-8H-吡啶并[4',3':4,5]噻吩并[3,2-f][1,2,4]三唑并[4,3-a][1,4]二氮杂卓（E-6123，CAS 131614-02-3）对微血管通透性、全身性低血压和肾病的影响。E-6123以3微克/千克口服给药后，可抑制豚鼠体内PAF注射诱导的微血管通透性（水肿）。与其他PAF拮抗剂相比，E-6123的抑制作用非常显著。E-6123以3微克/千克静脉给药后，可逆转大鼠体内PAF和/或内毒素注射诱导的低血压。腹腔注射氨基核苷诱导肾病的大鼠，口服10毫克/千克/天的E-6123并不能抑制其尿蛋白排泄的增加。
