Anti-cocaine catalytic antibodies--a novel approach to the problem of addiction.
Cocaine reinforces its self-administration in relation to the magnitude of and rate of rise to the peak serum concentration of the drug. Catalytic antibodies are artificial enzymes which could reduce serum cocaine concentrations, deprive the abuser of cocaine's reinforcing effect and thus favor extinction of the addiction. Catalytic antibodies are elicited by immunization with a stable analog of a transition-state for a chemical reaction. Through our new method for synthesizing phosphonate monoesters, we constructed several phosphonate-based transition-state analogs of cocaine hydrolysis. Using these analogs, monoclonal antibodies were elicited and, thus far, nine anti-analog antibodies with hydrolytic activity against cocaine have been identified, cloned and studied. The activity of one of these antibodies, 15A10, is sufficient to commence preclinical studies.
Landry
D W
DW
Department of Medicine, Columbia University, College of Physicians & Surgeons, New York, NY 10032, USA.
Yang
G X
GX
D000818:Animals; D017151:Antibodies, Catalytic / Q000032:analysis* / Q000627:therapeutic use; D002352:Carrier Proteins / Q000037:antagonists & inhibitors; D003042:Cocaine / Q000008:administration & dosage / Q000276:immunology*; D003216:Conditioning, Operant; D050483:Dopamine Plasma Membrane Transport Proteins; D006801:Humans; D008253:Macaca mulatta; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D012646:Self Administration; D019966:Substance-Related Disorders / Q000276:immunology* / Q000534:rehabilitation
D017151:Antibodies, Catalytic; D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D003042:Cocaine