The ability of human plasma butyrylcholinesterase (BChE) to detoxify c
ocaine in vivo was evaluated. Intravenous administration of BChE, at d
oses sufficient to increase the plasma levels of the enzyme as much as
800-fold, produced no adverse effects on the cardiovascular, autonomi
c, or central nervous systems of rats. Most of the enzyme could be rec
overed in the plasma immediately after administration and remained act
ive with a beta-t 1/2 of 21.6 +/- 2.4 hr. Pretreatment of chloralose-u
rethane anesthetized rats with BChE, 0.1-7.8 mg/kg, decreased the hype
rtensive and arrhythmogenic effects produced by cocaine and increased
the lethal dose of cocaine by three-to fourfold. Treatment of consciou
s rats with 1 and 10 mg/kg BChE decreased the incidence of seizures an
d deaths produced by a prior dose of cocaine (80 mg/kg, ip), These res
ults suggest that BChE would provide a safe and highly efficacious tre
atment for cocaine intoxication. (C) 1997 Academic Press.