A CATALYTIC ANTIBODY AGAINST COCAINE PREVENTS COCAINE REINFORCING ANDTOXIC EFFECTS IN RATS

Cocaine addiction and overdose have long defied specific treatment. To provide a new approach, the high-activity catalytic antibody mAb 15A1 0 was elicited using a transition-state analog for the hydrolysis of c ocaine to nontoxic, nouaddictive products. In a model of cocaine overd ose, mAb 15A10 protected rats from cocaine-induced seizures and sudden death in a dose-dependent fashion; a noncatalytic anticocaine antibod y did not reduce toxicity. Consistent with accelerated catalysis, the hydrolysis product ecgonine methyl ester was increased >10-fold in pla sma of rats receiving mAb 15A10 and lethal amounts of cocaine. In a mo del 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 reuptak e inhibitor bupropion. This artificial cocaine esterase is a rationall y designed cocaine antagonist and a catalytic antibody with potential for medicinal use.