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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。
Objective To investigate the permeability of the new highly effective antiarrhythmic drug, chlorobenzyl tetrahydropalmatine hydrochloride (CPU 86 0 17) to the blood-brain barrier and whether the brain is involved in the acute toxicity of CPU 86 0 17. Methods The LD50 of mice iv and icv were compared and the in vivo treatment in brain, heart, kidney and blood was determined by HPLC after giving lethal doses of 6.1 ml / kg (iv and icv) and compared. Results LD50 of iv and icv were close, suggesting that the brain and peripheral organs (heart) are associated with acute toxicity. After iv administration of 6.1 mg / kg, the concentrations in the heart and brain were 20.9 ± 6.2 and 1.18 ± 0.28 μg / mg, respectively, while the corresponding icv were 12 ± 6, 12 ± 7 μg The highest concentration after / mg.iv and icvCPU 86 0 17 occurred in the kidney. Conclusion The permeability of the brain from the brain to the systemic circulation is easier than that from the systemic circulation to the brain and penetrates the blood-brain barrier, indicating that the brain is also involved in its toxicity and pharmacology. The role of high concentrations in the kidney remains to be further studied .