EXPERIMENTAL ANALYSIS OF SEDATIVE/STIMULANT ABUSE

描述：（申请人摘要） 建议在有药物滥用史的受试者和正常受试者中进行研究。 受试者描述药物的药理学特征和滥用倾向 新的苯并二氮杂和非苯并二氮杂镇静-抗焦虑药。 一个系列 的实验将评估镇静抗焦虑药物的作用， 有镇静剂滥用史的志愿者， 住宅研究实验室。 这些研究将提供详细的 剂量效应、时间过程和相对效价数据， 行为、主观和强化效果的测量。 具体地说， 这些实验将比较不同剂量的三唑仑 或阿普唑仑与氟硝西泮、可乐定、苯环利定、甲基普仑。 一 同时进行的一系列非住宅实验将扩展以前的 研究加强，辨别刺激，和 受试者中苯二氮卓类药物的拮抗剂促戒断作用 没有吸毒史 一系列的研究将检查 通过调查正常受试者中 不同的苯二氮卓受体激动剂在 适度饮酒者，并通过研究个体的强化效应， 睡眠问题和焦虑 另一组研究将操纵剂量 和任务难度来扩展先前的研究表明， 苯二氮卓类药物的强化可以通过行为要求来调节， 在药物摄入后。 一项研究将使用药物辨别方法， 通过培训三唑仑、唑吡坦和安慰剂来区分药物 然后检测一系列苯二氮卓受体 激动剂 最后一组研究将描述拮抗剂沉淀 静脉和口服氟马西尼后停药， 有长期暴露于治疗剂量的受试者 苯二氮卓类 人们担心苯二氮卓类药物滥用和身体 多种药物滥用者和患者的依赖性。 最近的研究 苯二氮卓药理学的发展提高了 将这些药物的滥用和依赖活动与 各种其他行为和治疗作用。 这项研究将 提供有关行为和药理学机制的信息， 这些化合物的作用和相对滥用倾向。 本研究 应该有助于开发新的镇静抗焦虑药 降低药物滥用者滥用可能性的化合物，以及 降低患者长期不当用药的可能性。

DESCRIPTION: (Applicant's Abstract) Research is proposed in subjects with histories of drug abuse and in normal subjects to characterize the pharmacological profiles and abuse liability of novel benzodiazepine and nonbenzodiazepine sedative-anxiolytics. One series of experiments will assess the effects of sedative-anxiolytic drugs in volunteers with histories of sedative drug abuse who will reside on a residential research laboratory. These studies will provide detailed dose-effect, time-course and relative potency data across a wide range of measures of behavioral, subjective and reinforcing effects. Specifically, these experiments will compare the effects of a range of doses of triazolam or alprazolam with flunitrazepam, clonidine, phencyclidine, methyprylon. A concurrent series of nonresidential experiments will extend previous research examining the reinforcing, discriminative stimulus, and antagonist-precipitated withdrawal effects of benzodiazepines in subjects without histories of drug abuse. One series of studies will examine reinforcing effects in normal subjects by investigating differences in the reinforcing effects of different benzodiazepine receptor agonists in moderate drinkers, and by studying reinforcing effects in individuals with sleeping problems and anxiety. Another set of studies will manipulate dose and degree of task difficulty to extend previous research showing that benzodiazepine reinforcement can be modulated by the behavioral requirements following drug ingestion. One study will use drug discrimination methods to differentiate among drugs by training a triazolam vs. zolpidem vs. placebo discrimination and then testing a series of benzodiazepine receptor agonists. A final set of studies will characterize antagonist-precipitated withdrawal after intravenous and oral administration of flumazenil to subjects with histories of long-term exposure to therapeutic doses of benzodiazepines. There is concern about benzodiazepine abuse and physical dependence among polydrug abusers and patients. Recent research developments in benzodiazepine pharmacology raise the possibility of dissociating the abuse and dependence activity of these drugs from the various other behavioral and therapeutic actions. This research will provide information about behavioral and pharmacological mechanisms of action and relative abuse liability of these compounds. This research should contribute to efforts to develop new classes of sedative-anxiolytic compounds which have reduced potential for abuse by drug abusers as well as reduced potential for inappropriate chronic use among patients.