A catalytic antibody against cocaine prevents cocaine's reinforcing and toxic effects in rats.
Cocaine addiction and overdose have long defied specific treatment. To provide a new approach, the high-activity catalytic antibody mAb 15A10 was elicited using a transition-state analog for the hydrolysis of cocaine to nontoxic, nonaddictive products. In a model of cocaine overdose, mAb 15A10 protected rats from cocaine-induced seizures and sudden death in a dose-dependent fashion; a noncatalytic anticocaine antibody did not reduce toxicity. Consistent with accelerated catalysis, the hydrolysis product ecgonine methyl ester was increased >10-fold in plasma of rats receiving mAb 15A10 and lethal amounts of cocaine. In a model of cocaine addiction, mAb 15A10 blocked completely the reinforcing effect of cocaine in rats. mAb 15A10 blocked cocaine specifically and did not affect behavior maintained by milk or by the dopamine reuptake inhibitor bupropion. This artificial cocaine esterase is a rationally designed cocaine antagonist and a catalytic antibody with potential for medicinal use.
Mets
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B
Department of Anesthesiology, Columbia University, College of Physicians & Surgeons, 630 West 168th Street, New York, NY 10032, USA.
Winger
G
G
Cabrera
C
C
Seo
S
S
Jamdar
S
S
Yang
G
G
Zhao
K
K
Briscoe
R J
RJ
Almonte
R
R
Woods
J H
JH
Landry
D W
DW
D000818:Animals; D017151:Antibodies, Catalytic / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D003042:Cocaine / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity*; D004195:Disease Models, Animal; D006868:Hydrolysis; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012054:Reinforcement, Psychology; D012646:Self Administration; D019966:Substance-Related Disorders / Q000517:prevention & control*
D017151:Antibodies, Catalytic; D000911:Antibodies, Monoclonal; D003042:Cocaine