摘要
兔iv咪苯嗪酮(CI—914)20 mg/kg,用RIA法测定其血浆中TXB_2和6—kcto—PGF_(1α)含量,给药后30 min和60 min.6—keto—PGF_(1α)/TXB_2比值显著升高(p<0.05).在用放射性TLC法进行的洗涤大鼠血小板^(14)C—AA代谢实验中,CI—914在2～500 μmol/L范围内以剂量依赖方式抑制大鼠血小板TXB_2生成,IC_(50)为51.5μmol/L,对HHT生成的抑制明显弱于对TXB_2生成的抑制作用;在相同剂量范围内,CI—914同时以剂量依赖方式使PGE_2,PGF_(2α)和PGD_2生成增加.在相同实验条件下,50μmol/L的已知的TXA_2合成酶抑制剂DAZ,与大剂量CI—914的实验结果类似.上述结果提示,CI—914对血小板TXA_2合成酶可能具有选择性抑制作用.
The effects of CI-914,a novel type Ⅲ phosphodiesterase inhibitor with cardiotonic and anti-platelet aggregative activity,on thromboxane B2(TXB2)and 6-keto-prostaglandin F 1α(6-keto-PGF1α)levels in rabbit plasma and [1-14C] arachidonic acid(14C-AA)metabolism in washed platelets from rats were studied.CI-914 decreased TXB2 level (p<0.05)and increased 6-keto-PGF1α level (p<0.05)in plasma form couseious rabbits after iv admimstration of 20 mg/kg of the drug as compared with the control rabbits by radioimmunoassay.The influence of CI-914 on 14C-AA metabolism in washed rat platelets was determined by thin-layer radiochromatography,including thin-layer radio-scanning,autoradiography and liquid scitillation counting.In platelet suspensions stimulated with 14C-AA in vitro,TXB2content was reduced in a dose-dependent manner and a significant redirection of endoperoxide metabolism to prostaglandin E2,F2α,and D2was demonstrated after the addition of 2~ 500μmol/L CI-914.At the same doses,the inhibition of CI-914 on the formation of 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT)was lesser than that on TXB2 formation.Dazoxiben,a selective TXA2 synthetasc inhibitor,exhibited an action similar to CI-914 on the 14C-AA metabolism.It is strongly suggested that CI-914 may selectively inhibit TXA2 synthetase in platelets.
出处
《中国药理学与毒理学杂志》
CAS
CSCD
北大核心
1989年第2期85-90,共6页
Chinese Journal of Pharmacology and Toxicology
基金
上海市科技发展基金(编号86343096)
关键词
咪苯嗪酮
花生四烯酸
4,5-dihydro-6-[4-(1H-imidazol-1-yl)phenyl]-3(2H)-pyridazinone monohydrochloride (CI-914, imazodan)
arachidonic acid
thromboxane A2
pro-stacyclin
prostaglandins
radioimmunoassay
thin-layer chromatography
