Attenuation of cocaine-induced locomotor activity by butyrylcholinesterase.
A primary enzyme for the metabolism of cocaine is butyrylcholinesterase (BChE). To determine whether the systemic administration of BChE can increase the metabolism of cocaine sufficiently to alter a behavioral effect, rats were tested in a locomotor activity chamber after receiving 17 mg of cocaine per kg intraperitoneally. In rats pretreated intravenously with 5,000 IU of horse serum-derived BChE, the locomotor activity effect was significantly attenuated. BChE pretreatment increased plasma BChE levels approximately 400-fold. When added to rat plasma, this amount of BChE reduced the cocaine half-life from over 5 hr to less than 5 min. BChE altered the cocaine metabolic pattern such that the relatively nontoxic metabolite ecgonine methyl ester was produced, rather than benzoylecgonine. These results suggest that systemic administration of BChE can increase the metabolism of cocaine sufficiently to alter a behavioral effect of cocaine and thus should be investigated as a potential treatment for cocaine abuse.
Carmona
G N
GN
Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA. gcarmona@intra.nida.nih.gov
Schindler
C W
CW
Shoaib
M
M
Jufer
R
R
Cone
E J
EJ
Goldberg
S R
SR
Greig
N H
NH
Yu
Q S
QS
Gorelick
D A
DA
D000818:Animals; D002091:Butyrylcholinesterase / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D003042:Cocaine / Q000378:metabolism / Q000494:pharmacology*; D004347:Drug Interactions; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009294:Narcotics / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D009294:Narcotics; D002091:Butyrylcholinesterase; D003042:Cocaine