催醒宁在大鼠离体灌流肝脏中的生物转化

用离体大鼠肝脏灌流方法,研究了胆碱酯酶抑制剂CXN的生物转化过程。径HPLC分离纯化及光谱分析,鉴定了CXN的六个脂溶性代谢产物的化学结构。产物Ⅰ为CXN原形,其余均为氧化产物。其中产物Ⅲ尚保留部分抑酶活力,而产物Ⅱ,Ⅴ及Ⅵ对小鼠全脑胆碱酯酶的抑酶活力明显下降。另外还观察到,代谢产物Ⅱ及Ⅴ对小鼠的急性毒性也明显减小。

THE BIOTRANSFORMATION OF CUI XING NING IN THE ISOLATED PERFUSED RAT LIVER

Similar to eserine, Cui Xing Ning CXN),5-(1,3,3-trimethylindoline) N, N-dimethyl carbamate] is a choline esterase (ChE) inhibitor. The biotransformation of CXN, which had been studied in vivo and in vitro unsuccessfully, was studied by using isolated perfused rat liver (IPL) method. Six metabolites of CXN from the perfusate were separated by HPLC, and identified with MS, 1HNMR or compared with the authentic compounds. Metabolite I is unchanged CXN, the other are oxidized metabolites. Most of the metabolites lost their activities of ChE inhibition strikingly except metabolite III which retained the 2-position unchanged. The toxicities of some metabolites (II,V) decreased obviously.