THE EFFECT OF COCAETHYLENE ON RESPONSES TO COCAINE

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。本研究的目的是开始确定可卡因激动剂替代可卡因乙烯治疗可卡因依赖是否安全有效。可卡因依赖是一种药物治疗的新方法。可卡因依赖是一种物质使用障碍，到目前为止还没有批准的药物治疗。治疗药物依赖的一种方法是服用可以替代患者依赖的药物的药物。这一战略的成功实施取决于几个因素。这些替代药物应该在与滥用药物相关的强化效应和/或戒断症状的同一部位(S)和/或受体(S)发挥作用，并且应该比患者依赖的药物作用的时间更长。替代剂应减少或诱导对被滥用药物的影响的耐受性。然后，替代品将减少或消除对个人和整个社会具有如此破坏性的寻求毒品行为。使用一种可以阻断可卡因效应和/或对可卡因产生耐受性并且可以在临床药物滥用治疗环境中使用的药物，类似于目前美沙酮治疗海洛因依赖的模式，是治疗可卡因依赖的一种新方法。最近的流行病学数据显示，虽然吸食可卡因的绝对新增人数已经稳定下来，但因使用可卡因引起的急性医疗和精神并发症而去急诊室就诊的人数自1988年以来增加了两倍，这表明需要对可卡因依赖进行更深入的治疗。这项研究将测试替代治疗可卡因依赖将减少或阻止急性可卡因给药的影响的概念。这项研究将使用可可乙烯、苯甲酰ecGonine的乙酯和原型苯甲酰氧基托烷作为可卡因的替代品来测试这一概念。在人类研究中，可卡因被发现具有与可卡因相似的作用(6-8)，但在血浆浓度约为可卡因的两倍时，可卡因的效力低于可卡因，产生类似的心血管和行为影响。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The purpose of this study is to begin the process of determining whether cocaine agonist, substitution, therapy with cocaethylene is a safe and efficacious treatment for cocaine dependence. Cocaethylene may represent a novel approach to the pharmacotherapy of cocaine dependence, a substance use disorder with no approved pharmacotherapy to date. One approach to the treatment of drug dependence is to administer drugs that can substitute for the drug on which the patient is dependent. The successful implementation of such a strategy depends on several factors. These substitution agents should exert their effects at the same site(s) and/or receptor(s) responsible for the reinforcing effects and/or withdrawal symptoms associated with the abused drug and should be longer acting than the drug on which the patient is dependent. Substitution agents should diminish effects or induce tolerance to the effects of the drug that is being abused. Substitution agents would then reduce or eliminate the drug-seeking behaviors so destructive to the individual and society at large. The use of a drug that could block and/or produce tolerance to cocaine effects and that could be administered in a clinical drug abuse treatment setting similar to the present model of methadone treatment of heroin dependence represents a novel approach to the treatment of cocaine dependence. Recent epidemiological data show that while absolute new numbers of cocaine users has stabilized, the number of emergency room visits for acute medical and psychiatric complications from cocaine use have tripled since 1988, indicating a need for more intensive treatment of cocaine dependence. This study will test the concept that substitution treatment for cocaine dependence will reduce or block the effects of acute cocaine administration. This study will test this concept using cocaethylene, the ethyl ester of benzoylecgonine and a prototype benzoyloxytropane, as the cocaine substitution agent. Cocaethylene has been found to have effects similar to cocaine in human studies (6-8), but cocaethylene is less potent than cocaine at plasma concentrations about twice those produced by a comparator dose of cocaine producing similar cardiovascular and behavioral effects.