EVALUATION OF PROTEIN BASED MEDICATIONS AGAINST COCAINE

描述：（申请人摘要）用于治疗的药物疗法 可卡因滥用是很难识别的传统 受体拮抗剂方法似乎不适合可卡因， 原因很多。该建议旨在评估五种基于蛋白质的 可能有效阻断行为和毒性作用的药物 可卡因。其中三种药物是抗体， 在老鼠身上对抗可卡因第四种药物是丁酰胆碱酯酶， 分解血液中可卡因的酶。第五种药物是一种新的药物 催化性抗体，Mab 15 A10，其可结合联合收割机的结合特性， 新陈代谢这些药物中的每一种都被认为可以降低 可卡因进入大脑，要么通过隔离过程，要么通过 快速分解或两者兼而有之。大脑进入的速度下降 应降低可卡因的毒性和滥用倾向。测试 毒性程序包括评价几种剂量的 这些药物中的每一种都能阻止可卡因引起的血压升高， 大鼠和小鼠。作为对照，使用具有类似结构和作用的药物， 可卡因，但没有BChE和Mab 15A10作用的雌激素桥， 与可卡因平行评估。可卡因拮抗作用的持续时间， 药物的关键方面，将使用血压进行评估 在小鼠中的测定。治疗可卡因滥用的测试程序是 大鼠静脉内自我给药研究。同样，剂量反应曲线 与可卡因和WIN 35065将建立，并试图改变这些 曲线的权利将与管理的每五个 药物治疗BChE和Mab 15A10产生BChE的能力的研究 可卡因代谢物egconine甲酯的增加计划， 证明这两种药物都会增加可卡因的使用率 新陈代谢.

DESCRIPTION: (Applicant's Abstract) Pharmacotherapies useful in the treatment of cocaine abuse have proven very difficult to identify. The traditional receptor antagonist approach does not appear appropriate for cocaine for a number of reasons. This proposal is designed to evaluate five protein-based medications that may be effective in blocking the behavioral and toxic effects of cocaine. Three of these medications are antibodies that have been raised against cocaine in mice. A fourth medication is butyrylcholinesterase, the enzyme that breaks down cocaine in the blood. The fifth medication is a novel catalytic antibody, Mab 15A10, which may combine the properties of binding and metabolizing. Each of these medications is postulated to act to reduce the rate of cocaine entry into the brain, either by a process of sequestration, or by a process of rapid breakdown, or both. This decrease in rate of brain entry should decrease both the toxicity and the abuse liabililty of cocaine. The test procedures for toxicity involve evaluation of the ability of several doses of each of these medications to block cocaine-induced blood pressure increases in rats and mice. As a control, a drug with a similar structure and action as cocaine, but without the esteratic bridge where BChE and Mab 15A10 act, will be evaluated in parallel with cocaine. The duration of cocaine antagonism, a critical aspect of a medication, will be evaluated using the blood pressure assay in mice. The test procedure for treatment of the abuse of cocaine is intravenous self-administration studies in rats. Here too, dose-response curves with cocaine and WIN 35065 will be established, and attempts to shift these curves to the right will be made with administration of each of the five medications. Studies in which the ability of BChE and Mab 15A10 to produce increases in the cocaine metabolite, egconine methyl ester are planned to demonstrate that both of these medications increase the rate of cocaine metabolism.