Young R, Glennon R A, Brase D A, Dewey W L
Life Sci. 1986 Jul 7;39(1):17-20. doi: 10.1016/0024-3205(86)90432-7.
The dose-response relationships of diazepam and several of its metabolites were determined in rats trained to discriminate diazepam (3 mg/kg) from saline in a two-lever operant choice task. Generalization of the diazepam stimulus was found to occur with temazepam and oxazepam, which were nearly equipotent with diazepam, and also with desmethyldiazepam, which was about half as potent as diazepam. The hydroxylated metabolites, 4'-hydroxydiazepam and 4'-hydroxydesmethyldiazepam were inactive in doses up to 12 mg/kg. These results show that some diazepam metabolites are quite potent behaviorally and indicate the possibility that these metabolites may contribute to the pharmacological effect of diazepam in vivo.
在一项双杠杆操作性选择任务中，对经过训练能区分地西泮（3毫克/千克）和生理盐水的大鼠，测定了地西泮及其几种代谢物的剂量-反应关系。发现地西泮刺激的泛化现象出现在替马西泮和奥沙西泮身上，它们与地西泮几乎等效，去甲地西泮也出现了这种现象，其效力约为地西泮的一半。羟基化代谢物4'-羟基地西泮和4'-羟基去甲地西泮在高达12毫克/千克的剂量下没有活性。这些结果表明，一些地西泮代谢物在行为上相当有效，并表明这些代谢物可能在体内对地西泮的药理作用有贡献。
