EXPERIMENTAL ANALYSIS OF SEDATIVE/STIMULANT ABUSE

描述：(申请人摘要) 建议对有吸毒史和正常情况的受试者进行研究。 描述其药理学特征和滥用倾向的对象 新型苯二氮卓类和非苯二氮卓类镇静抗焦虑药。一个系列 的实验将评估镇静和抗焦虑药物在 有镇静剂滥用史的志愿者将居住在 住宅区研究实验室。这些研究将提供详细的 广泛范围内的剂量效应、时间进程和相对效力数据 衡量行为效果、主观效果和强化效果。具体来说， 这些实验将比较不同剂量的三唑仑的效果。 或阿普唑仑配伍氟硝西潘、可乐定、苯环利定、甲基苯丙胺。一个 同时进行的一系列非住宅实验将延长之前的 研究考察了增强性、歧视性刺激和 苯二氮类药物在受试者的拮抗剂催促戒断效应 没有吸毒史。一系列研究将检验 在正常受试者中观察增强效应的差异 不同苯二氮卓类受体激动剂的增强作用 适度饮酒的人，并通过研究增强饮酒者的效果 睡眠问题和焦虑。另一组研究将操纵剂量 和任务难度的程度来扩展之前的研究表明 苯二氮卓类药物强化可根据行为要求进行调节 在吸食毒品之后。一项研究将使用药物歧视方法来 通过训练三唑仑、唑吡坦和安慰剂来区分药物 辨别并检测一系列苯二氮卓类受体 激动剂。最后一组研究将描述对手沉淀的特征 氟马西尼静脉和口服给药后停药 有治疗剂量长期接触史的受试者 苯二氮卓类。人们对苯二氮类药物的滥用和身体健康感到担忧 多药滥用者和患者的依赖情况。最新研究 苯二氮卓类药物药理学的发展增加了 将这些药物的滥用和依赖活动与 各种其他行为和治疗行为。这项研究将 提供有关行为和药理机制的信息 这些化合物的行为和相对滥用责任。这项研究 应有助于开发新的镇静-抗焦虑药物类别 减少吸毒者滥用可能性的化合物以及 降低了患者不适当长期使用的可能性。

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.