盐酸三环哌酯在大鼠体内外的代谢

IN VIVO AND IN VITRO METABOLISM OF TRICYCLOPINATE HYDROCHLORIDE IN THE RAT

用大鼠原位灌流肝脏、整体实验和大鼠肝脏微粒体酶制备对盐酸三环哌酯（ＴＣＰＮ）的代谢转化进行了研究。结果经大鼠原位肝脏灌流后，灌流液经提取和ＨＰＬＣ分离制备，得到两个代谢产物。经ＭＳ，ＮＭＲ，ＩＲ和ＵＶ鉴定，证明产物Ｉ是ＴＣＰＮ氮上脱甲基的产物，产物Ｉ是ＴＣＰＮ苯环羟化的产物。从大鼠ｉｇＴＣＰＮ后的尿中及在ＴＣＰＮ和肝脏微粒体的温孵液中均得到产物Ｉ和产物ＩＩ，提示ＴＣＰＮ的代谢转化主要由大鼠肝脏微粒体酶催化。以［３Ｈ］ＱＮＢ为配体对ＴＣＰＮ及其代谢产物的受体结合活性进行了研究，结果表明产物Ｉ和产物Ｉ与Ｍ受体的亲和力分别是ＴＣＰＮ的１／２０和１／５０。

The metabolism of tricyclopinate hydrochloride(TCPN), a new anticholinergic agent, was studied by in situ perfused rat liver preparation. Two metabolites were isolated by HPLC. Metabolite I was identified as an N demethylation product, while metabolite II was shown to be an arylhydroxylation product. Metabolite I and metabolite II were also isolated from the urine of the rat given TCPN ig. This result shows that the two metabolites from the perfused rat liver are just the final metabolites produced in vivo . The metabolites in rat liver microsomes were also identified as those just described. These results suggest that the biotransformation reaction of TCPN is mainly catalyzed by the enzyme in rat liver microsomes. The results of experiment on receptor activity indicate that the action potency with mAChR of metabolite I and metabolite II was only 1/20 and 1/50, respectively, of that of TCPN.