Cocaine detoxification by human plasma butyrylcholinesterase

被引:81
作者
Lynch, TJ
Mattes, CE
Singh, A
Bradley, RM
Brady, RO
Dretchen, KL
机构
[1] PHARMAVENE INC, GAITHERSBURG, MD 20850 USA
[2] GEORGETOWN UNIV, MED CTR, DEPT PHARMACOL, WASHINGTON, DC 20007 USA
关键词
D O I
10.1006/taap.1997.8187
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The ability of human plasma butyrylcholinesterase (BChE) to detoxify cocaine in vivo was evaluated. Intravenous administration of BChE, at doses sufficient to increase the plasma levels of the enzyme as much as 800-fold, produced no adverse effects on the cardiovascular, autonomic, or central nervous systems of rats. Most of the enzyme could be recovered in the plasma immediately after administration and remained active with a beta-t 1/2 of 21.6 +/- 2.4 hr. Pretreatment of chloralose-urethane anesthetized rats with BChE, 0.1-7.8 mg/kg, decreased the hypertensive and arrhythmogenic effects produced by cocaine and increased the lethal dose of cocaine by three-to fourfold. Treatment of conscious rats with 1 and 10 mg/kg BChE decreased the incidence of seizures and deaths produced by a prior dose of cocaine (80 mg/kg, ip), These results suggest that BChE would provide a safe and highly efficacious treatment for cocaine intoxication. (C) 1997 Academic Press.
引用
收藏
页码:363 / 371
页数:9
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