COCAETHYLENE COCAINE AGONIST THERAPY/TOLERANCE INDUCTION

描述：寻找一种有效的药物疗法来治疗癌症 可卡因依赖一直难以捉摸，但严重的医疗和心理问题 可卡因滥用的发病率和社会代价突出表明有必要继续 可卡因药物开发领域的研究。在此应用程序中， 我们建议进行研究，以确定可卡因激动剂(替代)疗法是否 用C2取代的可卡因的苯甲氧基托烷类似物可能是安全的 作为治疗可卡因依赖的药物疗法是有效的。C2 取代的可卡因类似物，同时与 可卡因，具有其他不同的特性，可能使它们用作 治疗可卡因依赖的药物治疗药物。我们建议使用 可可烯，苯甲酰ecGonine的C2乙酯，作为治疗 测试激动剂治疗可能阻断和/或产生耐受性的概念 可卡因的急性影响。这项提案将研究 受试者服用可可乙烯的安全性考察 可卡因的药代动力学、生理和行为反应 在注射了这种药物之后。还基于以下方面开发了一个范例 临床前研究显示诱导对急性可卡因反应的耐受性 在啮齿类动物身上，这将在人类受试者身上进行。该协议将 确定对心血管疾病的耐受性和主观反应 可卡因可以在注射可卡因后被诱导。积极的调查结果来自 这些研究可以在未来的研究中进行临床试验，以 评估这类药物治疗可卡因的疗效 依赖。

DESCRIPTION: The search for an effective pharmacotherapy for the treatment of cocaine dependence has been elusive, but the serious medical and psychological morbidity and social costs of cocaine abuse underscore the need to continue research in the area of cocaine medications development. In this application, we propose studies to determine whether cocaine agonist (substitution) therapy with C2 substituted benzoyloxytropane analogs of cocaine might be safe and efficacious as pharmacotherapy treatments for cocaine dependence. The C2 substituted cocaine analogs, while sharing some pharmacological properties with cocaine, have other dissimilar properties that potentially make them useful as pharmacotherapeutic agents to treat cocaine dependence. We propose to use cocaethylene, the C2 ethyl ester of benzoylecgonine, as a prototype drug to test the concept that agonist treatment may block and/or produce tolerance to the acute effects of cocaine. This proposal will examine the question of the safety of cocaethylene administered to volunteers by examination of cocaethylene pharmacokinetics, physiological, and behavioral responses following infusion of the drug. A paradigm has also been developed based on preclinical studies showing induction of tolerance to acute cocaine responses in rodents which will be undertaken in human subjects. This protocol will determine whether tolerance to cardiovascular and subjective responses to cocaine can be induced following cocaethylene infusion. Positive findings from these studies could be followed in future studies with clinical trials to assess the efficacy of this class of drugs in the treatment of cocaine dependence.