title: Predicting the clinical efficacy and potential adverse effects of a humanized anticocaine monoclonal antibody.
abstract: The effects of a humanized monoclonal antibody (mAb) having high affinity and specificity for cocaine in animal models are reviewed. The mAb reduced the concentration of cocaine in the brain of mice after intravenous injection of cocaine. In addition, the mAb increased the concentration of cocaine required to reinstate cocaine self-administration. These effects may predict clinical efficacy of a passive immunotherapy for reducing the probability of cocaine-induced relapse. However, in the presence of the mAb, once cocaine self-administration was reinstated, the consumption rate of cocaine was increased. This effect is hypothesized to result from a pharmacokinetic/pharmacodynamic interaction. A humanized mAb should minimize adverse events related to the immunogenicity of the mAb protein, and the specificity for cocaine should avoid adverse events related to interactions with physiologically relevant endogenous proteins.
authors.affiliation: Department of Pharmacology & Cell Biophysics and Department of Psychiatry & Behavioral Neuroscience, College of Medicine, University of Cincinnati, Cincinnati, OH 45237-0506, USA. andrew.norman@uc.edu
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Norman
authors.forename: William J
authors.initials: WJ
authors.lastname: Ball
mesh_terms: D000779:Anesthetics, Local / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000276:immunology / Q000493:pharmacokinetics; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use; D001921:Brain / Q000276:immunology / Q000378:metabolism; D003042:Cocaine / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000276:immunology / Q000493:pharmacokinetics; D019970:Cocaine-Related Disorders / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D004195:Disease Models, Animal; D006801:Humans; D007116:Immunization, Passive; D051379:Mice
chemical_list: D000779:Anesthetics, Local; D061067:Antibodies, Monoclonal, Humanized; D003042:Cocaine