Roache J D, Griffiths R R
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.
J Pharmacol Exp Ther. 1987 Dec;243(3):978-88.
On a residential research ward, the acute effects of placebo, lorazepam (LZ) (1.5-9.0 mg) and meprobamate (MEP) (600-3600 mg) were examined using a within-subject double-blind Latin Square design in nine male subjects with histories of drug abuse. Drug effects were assessed with objective performance tasks, subject estimates of performance, staff ratings of drug effects and subject ratings of drug effects, sleep, mood, drug liking and monetary street value. Generally, both LZ and MEP produced comparable dose-related effects; LZ had a more rapid onset of action and on several measures showed a more shallow dose-response curve than MEP. With LZ, but not MEP, subjects under-estimated the degree to which their performance was impaired and under-rated drug effects as compared to analogous staff ratings. Both drugs produced sedation-like subject ratings of mood and sleep but generally did not produce tranquilization-like ratings. MEP produced subject ratings of drug liking and monetary street value which were equal to or in some cases greater than those of LZ. Relative potency estimations showed that LZ was 510 to 783 times more potent than MEP in producing performance impairment but was only 370 times more potent than MEP in producing subject ratings of drug liking. Overall, these data indicate that the likelihood of abuse of MEP is at least equal to if not greater than that of LZ although LZ may have a greater likelihood of producing adverse behavioral effects such as a performance impairment and under-estimates of the degree of impairment. These data in conjunction with previous results from this laboratory show that the behavioral effects of benzodiazepines can be differentiated from those of other types of sedative/anxiolytics and that MEP displays characteristics of a barbiturate-like profile of action.
在一个住院研究病房中,采用受试者内双盲拉丁方设计,对9名有药物滥用史的男性受试者进行了安慰剂、劳拉西泮(LZ)(1.5 - 9.0毫克)和甲丙氨酯(MEP)(600 - 3600毫克)的急性效应研究。通过客观表现任务、受试者对表现的估计、工作人员对药物效应的评分以及受试者对药物效应、睡眠、情绪、药物喜好和金钱街值的评分来评估药物效应。一般来说,LZ和MEP都产生了类似的剂量相关效应;LZ起效更快,在几项指标上显示出比MEP更浅的剂量反应曲线。与类似的工作人员评分相比,使用LZ时受试者低估了其表现受损的程度,且对药物效应的评分较低,但使用MEP时并非如此。两种药物都产生了类似镇静的情绪和睡眠受试者评分,但一般没有产生类似安定的评分。MEP产生的受试者对药物喜好和金钱街值的评分等于或在某些情况下高于LZ。相对效价估计表明,LZ在导致表现受损方面比MEP强510至783倍,但在产生受试者对药物喜好的评分方面仅比MEP强370倍。总体而言,这些数据表明,MEP滥用的可能性至少与LZ相当,甚至可能更大,尽管LZ可能更有可能产生不良行为效应,如表现受损和对受损程度的低估。这些数据与该实验室之前的结果相结合表明,苯二氮䓬类药物的行为效应可以与其他类型的镇静/抗焦虑药物的行为效应区分开来,并且MEP表现出类似巴比妥类药物的作用特征。