Development of Esterases for the Treatment of Cocaine Overdose and Abuse

开发用于治疗可卡因过量和滥用的酯酶

基本信息

批准号：
7615518
负责人：
james H Woods
金额：
$ 70.52万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-05-10 至 2010-04-30
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Cocaine esterase (CocE) is a product of the bacterium Rhodococcus sp. which grows in the rhizosphere of coca plants in South America. The bacterium uses cocaine as its sole source of carbon and nitrogen, synthesizing CocE to initiate metabolism of the cocaine CocE is the most efficient enzyme (7.2 X 108) for metabolizing cocaine yet identified. It can both prevent and reverse extreme cocaine toxicity in our rodent models, and it has the potential to be developed into the first useful antagonist of cocaine's toxic effects. This proposal contains studies to continue to evaluate this enzyme in mouse and rat models of cocaine toxicity, to compare its effects with other protein-based anti-cocaine enzymes, and to use a variety of in vitro techniques, including pegylation and insertion into red blood cells, to improve this or other enzymes by reducing their antigenicity, and heat liability. These procedures are designed to prolong the enzyme's duration of action with the hopeful outcome that some insight will be obtained into how to make this substance useful in the long-term treatment of cocaine abuse.

描述（由申请人提供）：可卡因酯酶（COCE）是犀牛细菌的产物。它在南美可口可乐植物的根际生长。该细菌使用可卡因作为其唯一的碳和氮来源，合成COCE来启动可卡因CoCE的代谢是最有效的酶（7.2 x 108），用于代谢可卡因尚未确定。它可以预防和逆转我们啮齿动物模型中的极端可卡因毒性，并且有可能发展成为可卡因毒性作用的第一个有用的拮抗剂。该提议包含在可卡因毒性的小鼠和大鼠模型中继续评估这种酶的研究，将其与其他基于蛋白质的抗可卡因酶进行比较，并使用多种体外技术，包括Pegylation和插入红细胞中，以改善这种或其他酶来降低其抗纤维性，并进行抗纤维易受性易受益。这些程序旨在延长酶的作用持续时间，并希望获得一些洞察力，即如何使该物质在长期治疗可卡因滥用方面有用。

项目成果

期刊论文数量（11）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Prevention and reversal by cocaine esterase of cocaine-induced cardiovascular effects in rats.

DOI：
10.1016/j.drugalcdep.2009.09.001
发表时间：
2010-01-15
期刊：
Drug and alcohol dependence
影响因子：
4.2
作者：
Wood SK;Narasimhan D;Cooper Z;Sunahara RK;Woods JH
通讯作者：
Woods JH

Effects of cocaine esterase following its repeated administration with cocaine in mice.

DOI：
10.1016/j.drugalcdep.2009.01.002
发表时间：
2009-05-01
期刊：
DRUG AND ALCOHOL DEPENDENCE
影响因子：
4.2
作者：
Ko, Mei-Chuan;Narasimhan, Diwahar;Berlin, Aaron A.;Lukacs, Nicholas W.;Sunahara, Roger K.;Woods, James H.
通讯作者：
Woods, James H.

Bacterial cocaine esterase: a protein-based therapy for cocaine overdose and addiction.

DOI：
10.4155/fmc.11.194
发表时间：
2012-02
期刊：
Future medicinal chemistry
影响因子：
4.2
作者：
Narasimhan D;Woods JH;Sunahara RK
通讯作者：
Sunahara RK

Effects of a long-acting mutant bacterial cocaine esterase on acute cocaine toxicity in rats.

DOI：
10.1016/j.drugalcdep.2011.03.015
发表时间：
2011-11-01
期刊：
DRUG AND ALCOHOL DEPENDENCE
影响因子：
4.2
作者：
Collins, Gregory T.;Zaks, Matthew E.;Cunningham, Alyssa R.;Clair, Carley St.;Nichols, Joseph;Narasimhan, Diwahar;Ko, Mei-Chuan;Sunahara, Roger K.;Woods, James H.
通讯作者：
Woods, James H.

Amelioration of the cardiovascular effects of cocaine in rhesus monkeys by a long-acting mutant form of cocaine esterase.