Intravenous butyrylcholinesterase administration and plasma and brain levels of cocaine and metabolites in rats.
Butyrylcholinesterase is a major cocaine-metabolizing enzyme in humans and other primates, catalyzing hydrolysis to ecgonine methylester. Increasing butyrylcholinesterase activity may be a treatment for cocaine addiction. We evaluated the effect of 30-min pretreatment with horse-derived butyrylcholinesterase (5-15,000 U i.v.) or with the selective butyrylcholinesterase inhibitor cymserine (10 mg/kg i.v.) on the metabolism of cocaine (17 mg/kg i.p.) in anesthetized rats. Venous blood samples were collected for two hours after cocaine administration and later assayed for cocaine and metabolites by gas chromatography/mass spectroscopy. Whole brains were collected after the last blood sample and similarly assayed. Butyrylcholinesterase significantly increased plasma and brain ecgonine methylester levels and decreased cocaine plasma half-life from 26.2 min (saline) to 16.4 min (15,000 U). Butyrylcholinesterase had no significant effect on plasma or brain cocaine or benzoylecgonine levels. Cymserine had no effect on any variable. These findings suggest that butyrylcholinesterase treatment may have benefits in enhancing cocaine metabolism and in increasing levels of ecgonine methylester, which may have a protective action against cocaine.
Carmona
Gilberto N
GN
Intramural Research Programs, National Institute on Drug Abuse, Baltimore, MD 21224, USA.
Schindler
Charles W
CW
Greig
Nigel H
NH
Holloway
Harold W
HW
Jufer
Rebecca A
RA
Cone
Edward J
EJ
Gorelick
David A
DA
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002091:Butyrylcholinesterase / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D003042:Cocaine / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D008401:Gas Chromatography-Mass Spectrometry; D006207:Half-Life; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics
D002800:Cholinesterase Inhibitors; D014662:Vasoconstrictor Agents; C005618:benzoylecgonine; D002091:Butyrylcholinesterase; D003042:Cocaine; C034524:ecgonine methyl ester