Effects of a long-acting mutant bacterial cocaine esterase on acute cocaine toxicity in rats.
Effects of a long-acting mutant bacterial cocaine esterase on acute cocaine toxicity in rats.
复制标题
DOI：
10.1016/j.drugalcdep.2011.03.015
复制
发表时间：
2011-11-01
影响因子：
4.2
通讯作者：
Woods, James H.
中科院分区：
文献类型：
--
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.
一种作用时间更长的双突变细菌可卡因酯酶(Coce T172R/G173Q；DM Coce)已被证明可以保护小鼠免受可卡因诱导的死亡，抑制可卡因对大鼠的增强作用，并逆转可卡因对恒河猴的心血管效应。目前的研究评估了DM Coce在预防和逆转可卡因对雄性和雌性大鼠的心血管、惊厥和致死作用方面的有效性。通过预先实验确定DM Coce对急性可卡因中毒引起的心血管改变、惊厥和致死的保护作用的有效性和体内持续时间。治疗后的研究被用来评估DM Coce从大剂量可卡因的心血管和致死效应中拯救大鼠的能力。此外，还对雄性和雌性大鼠进行了研究，以确定性别是否对DM Coce保护或逆转大鼠急性可卡因中毒的能力有任何潜在影响。DM Coce可剂量依赖地保护大鼠免受可卡因引起的心血管改变、惊厥和致死，高剂量的保护作用长达4小时，并将可卡因诱导的致死至少向右移动10倍。除了剂量依赖地使大鼠从致死剂量的可卡因中恢复过来外，用DM Coce治疗后还逆转了可卡因对心血管的影响。在DM Coce预防或逆转急性可卡因中毒的有效性方面没有性别相关的差异。总之，这些结果支持了DM Coce用于治疗急性可卡因中毒的开发。
A longer acting, double mutant bacterial cocaine esterase (CocE T172R/G173Q; DM CocE) has been shown to protect mice from cocaine-induced lethality, inhibit the reinforcing effects of cocaine in rats, and reverse cocaine’s cardiovascular effects in rhesus monkeys. The current studies evaluated the effectiveness of DM CocE to protect against, and reverse cocaine’s cardiovascular, convulsant, and lethal effects in male and female rats. Pretreatment studies were used to determine the effectiveness and in vivo duration of action for DM CocE to protect rats against the occurrence of cardiovascular changes, convulsion and lethality associated with acute cocaine toxicity. Posttreatment studies were used to evaluate the capacity of DM CocE to rescue rats from the cardiovascular and lethal effects of large doses of cocaine. In addition, male and female rats were studied to determine if there were any potential effects of sex on the capacity of DM CocE to protect against, or reverse acute cocaine toxicity in rats. Pretreatment with DM CocE dose-dependently protected rats against cocaine-induced cardiovascular changes, convulsion and lethality, with higher doses active for up to 4 hrs, and shifting cocaine-induced lethality at least 10-fold to the right. In addition to dose-dependently recovering rats from an otherwise lethal dose of cocaine, post-treatment with DM CocE also reversed the cardiovascular effects of cocaine. There were no sex-related differences in the effectiveness of DM CocE to protect against, or reverse acute cocaine toxicity. Together, these results support the development of DM CocE for the treatment of acute cocaine toxicity.
登录
查看更多内容
影响因子：
10.6
作者：
Haney, Margaret;Gunderson, Erik W.;Jiang, Huiping;Collins, Eric D.;Foltin, Richard W.
通讯作者：
Foltin, Richard W.
影响因子：
3.6
作者：
Cooper, Ziva D.;Narasimhan, Diwahar;Woods, James H.
通讯作者：
Woods, James H.
影响因子：
3.6
作者：
Gao, Daquan;Narasimhan, Diwahar L.;Zhan, Chang-Guo
通讯作者：
Zhan, Chang-Guo
影响因子：
6.2
作者：
Haney, Margaret;Kosten, Thomas R
通讯作者：
Kosten, Thomas R
影响因子：
4.4
作者：
Bresler, MM;Rosser, SJ;Bruce, NC
通讯作者：
Bruce, NC