Lu X L, Yang S K
Department of Pharmacology, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799.
J Pharm Biomed Anal. 1993 Nov-Dec;11(11-12):1189-96. doi: 10.1016/0731-7085(93)80103-8.
Camazepam [3-(N,N-dimethyl)carbamoyloxy-7-chloro-1-methyl-1, 3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one, CMZ] possesses anxiolytic, anticonvulsant, muscle relaxant and hypnotic properties. CMZ is clinically used as a racemate. The enantioselective metabolism of racemic CMZ by rat liver microsomes was studied. Major metabolites were isolated by normal-phase and reversed-phase liquid chromatography (LC) and further characterized by UV absorption, mass, and circular dichroism spectral analyses, and by chiral stationary phase LC analysis. Following an in vitro incubation of rac-CMZ, the unmetabolized CMZ was found to be enriched (S)-CMZ, indicating that the R-enantiomer was enantioselectively metabolized. Two of the most abundant metabolites, formed by hydroxylation and demethylation of a methyl group of the N,N-dimethylcarbamyloxy side chain, were found to be enriched in the R-enantiomer. The results indicated that the (R)-CMZ was metabolized at a faster rate than (S)-CMZ by rat liver microsomes.
卡马西泮[3-(N,N-二甲基)氨甲酰氧基-7-氯-1-甲基-1,3-二氢-5-苯基-2H-1,4-苯并二氮杂卓-2-酮，CMZ]具有抗焦虑、抗惊厥、肌肉松弛和催眠特性。CMZ在临床上用作消旋体。研究了大鼠肝微粒体对消旋CMZ的对映体选择性代谢。通过正相和反相液相色谱(LC)分离主要代谢产物，并通过紫外吸收、质谱、圆二色光谱分析以及手性固定相LC分析进一步表征。在rac-CMZ进行体外孵育后，发现未代谢的CMZ富含(S)-CMZ，表明R-对映体被对映体选择性代谢。通过N,N-二甲基氨甲酰氧基侧链甲基的羟基化和去甲基化形成的两种最丰富的代谢产物被发现富含R-对映体。结果表明，大鼠肝微粒体对(R)-CMZ的代谢速率比对(S)-CMZ快。
