A catalytic antibody against cocaine prevents cocaine's reinforcing and toxic effects in rats

Berend Mets, Gail Winger, Camilo Cabrera, Susan Seo, Subhash Jamdar, Ginger Yang, Kang Zhao, Richard J. Briscoe, Rowena Almonte, James H. Woods, Donald W. Landry

Research output: Contribution to journalArticlepeer-review

119 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)10176-10181
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number17
DOIs
StatePublished - Aug 18 1998

ASJC Scopus subject areas

  • General

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