甲基及去甲基洛土辛对离体心肌及大鼠血流动力学的影响  

Influlence of methyl-lotusine and demethyl-lotusine on physiological function of isolated myocardium and haemodynamics in anesthetized rats

作　　者：冯秀玲[1] 张延琳[1] 肖军花[1] 王嘉陵[1] 

机构地区：[1]华中科技大学同济医学院药理学教研室,湖北武汉430030

出　　处：《中国医院药学杂志》2002年第1期5-7,共3页Chinese Journal of Hospital Pharmacy

基　　金：湖北省科委科学基金资助项目 ;N0 .98-JJ -15 90

摘　　要：目的 :为寻求新型、高效磷酸二酯酶 (PDE)Ⅲ抑制剂并为进一步改构体提供依据 ,比较性研究PDE抑制药洛土辛 (lotusine ,Lot)、甲基洛土辛 (methly lotusine ,MLT)和去甲基洛土辛 (demethly lotusine ,DMLT)对离体心肌及大鼠血流动力学的影响。方法 :采用收缩张力及血流动力学记录法。结果 :MLT(1～ 30 0 μmol·L-1)或DMLT(1～ 10 0 μmol·L-1)可剂量依赖性地增加离体大鼠左心房肌及猫右室乳头肌收缩力 ,MLT效价低于Lot和DMLT ,但效能却高于后两者 ;Lot,DMLT的效价、效能与Lot相似。与Lot对HR无明显不同 ,两者均增快HR。与Lot相似 ,DMLT 5mg·kg-1,iv明显增高LVP、±dp/dtmax、SAP、DAP及HR ,且作用时间可维持约 2 5min左右。结论 :增加Lot化构中异喹啉及苄基上的甲基 (二甲氧基 )或去氮甲基对母体物正性肌力活性无本质影响 ,反致心率增快。OBJECTIVE To evaluate the potency and the maximum efficacy of lotusine(Lot),a novel phosphodiesterase inhibitor and methyl-lotusine(MLT) and demethyl-lotusine(DMLT), which derived from Lot. The effects of three compounds on physiological function of myocardium and hamodynamics were studied.METHOD Using contractile force and hamodynamics recording methods.RESULTS MLT(1～300 μmol·L -1 )and DMLT(1～100 μmol·L -1 ) could dose-dependently increased contractile force of rat left atrium and cat papillary muscles of right ventricle. The potency of MLT was lower than that of Lot and DMLT, while the maximum efficacy was higher. The potency and maximum efficacy of DMLT were similar to Lot. In addition, different from Lot, both DMLT and MLT increased heart rate. In anesthetized rats, DMLT and Lot 5 mg·kg -1 ,iv,significantly increased the LVP,dp/dt max ,SAP,DAP,and HR, which maintained for 25 minutes.CONCLUSIONS In chemical structure,increasing iso-quinoline and benzyl's methyl(two-oxygen methyl) or substituet-nitrogen methyl have no essential influence on positive force activity of pre-substance,to the contrary,thay can cause to increase heart rate.

关 键 词：去甲基洛土辛 离体心肌 洛土辛 甲基洛土辛 血流动力学 

分 类 号：R972.4[医药卫生—药品]