小鼠iv及icv氯苄基四氢小檗碱(CPU-86017)的血脑屏障及体内处置(英文)  

Disposition and Blood Brain Barrier of CPU-86017(p-Chlo-robenzyltetrahydroberberine) after iv and icv in mice.

作　　者：查马拉[1] 林生[1] 刘文涛[1] 戴德哉[1] 

机构地区：[1]中国药科大学药理研究室,南京210009

出　　处：《中国药科大学学报》2002年第3期226-230,共5页Journal of China Pharmaceutical University

基　　金：国家自然科学基金资助项目 (No .396 70 835 )~~

摘　　要：目的　探讨新的高效抗心律失常药氯苄基四氢小檗碱盐酸盐 (CPU 86 0 17)对血脑屏障的穿透性 ,以及脑是否亦参与CPU 86 0 17的急性毒性。方法　对小鼠iv和icv的LD50 进行了比较 ,在给致死剂量 6 .1ml/kg(iv和icv)之后 ,利用HPLC测定脑 ,心脏 ,肾以及血液中的体内处置并进行了比较。结果　iv和icv的LD5 0接近 ,提示脑和外周器官 (心脏 )与急性毒性有关。iv给药 6 .1mg/kg之后 ,心脏和脑中的浓度分别为 2 0 .9± 6 .2和 1.18± 0 .2 8μg/mg ,而相应的icv的分别为 12± 6 ,12± 7μg/mg.iv和icvCPU 86 0 17之后的最高浓度出现在肾中。结论　CPU 86 0 17从脑到体循环的穿透性比从体循环到脑的穿透性要容易 ,能穿透血脑屏障 ,表明脑亦参与其毒性和药理作用 .肾中高浓度的作用有待进一步研究。AIM\ The purpose is to explore the permeability of p Chlorobenzyltetrahydroberberine hydrochloride (CPU 86017), a potent new antiarrhythmic agent, through the blood brain barrier (BBB) and to investigate whether the brain is involved in the acute toxicity of CPU 86017. METHODS\ The LD\-\{50\} by iv and icv (intracerebroventricular) was compared and disposition in brain, heart, kidney and blood was determined and compared, by validated HPLC assay following 6.1 mg·kg\+\{-1\} iv and icv, against mortality in mice.RESULTS\ The LD\-\{50\} between iv and icv was closed. The sedative effect was evident after both iv and icv medications. Concentrations in the heart and brain after medication of 6.1 mg·kg\+\{-1\} were 20.9±6.2 and 1.18±0.28 μg·mg\+\{-1\} by iv and 12±6 and 12±7 μg·mg\+\{-1\} by icv. The highest concentration of CPU 86017 after iv and icv was found in the kidney against the plasma concentrations. CONCLUSION\ The penetration of CPU 86017 through the BBB was easier from the brain to the general circulation than the reverse way. This permeability indicates that the brain is also involved in its toxic and pharmacological action. The role of the high concentration in the kidney remains to be investigated.

关 键 词：氯苄基四氢小檗碱 CPU-86017 HPLC 脑 药动学 毒性 小鼠 抗心律失常药 

分 类 号：R965[医药卫生—药理学]