THE EFFECT OF COCAETHYLENE ON RESPONSES TO COCAINE

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。本研究的目的是开始确定可卡因激动剂、可卡因替代物、可卡因乙烯治疗是否是一种安全有效的可卡因依赖治疗方法。可卡因依赖是一种物质使用障碍，迄今为止还没有批准的药物治疗，可卡因乙烯可能代表了一种新的药物治疗方法。 治疗药物依赖的一种方法是给药可以替代患者依赖的药物的药物。这种战略的成功实施取决于几个因素。这些替代剂应在与滥用药物相关的强化作用和/或戒断症状相同的部位和/或受体发挥作用，并且应比患者依赖的药物作用更长。替代剂应减少作用或诱导对正在滥用的药物的耐受性。替代药物将减少或消除对个人和整个社会具有破坏性的吸毒行为。使用一种可以阻断可卡因作用和/或产生对可卡因作用的耐受性的药物，并且可以在类似于目前美沙酮治疗海洛因依赖模型的临床药物滥用治疗环境中给药，这代表了治疗可卡因依赖的一种新方法。最近的流行病学数据表明，虽然可卡因使用者的绝对新人数已经稳定，但因可卡因使用引起的急性医疗和精神并发症而到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。 这项研究将测试的概念，可卡因依赖的替代治疗将减少或阻止急性可卡因管理的影响。本研究将测试这一概念使用cocaethylene，苯甲酰芽子碱的乙酯和原型苯甲酰氧基托烷，作为可卡因的替代剂。在人体研究中发现，古柯乙烯的作用与可卡因相似（6-8），但在血浆浓度约为对照剂量可卡因产生的两倍时，古柯乙烯的效力低于可卡因，产生类似的心血管和行为效应。

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.