title: Titer-dependent antagonism of cocaine following active immunization in rhesus monkeys.
abstract: Immunization may be a useful pharmacokinetic antagonist therapy for cocaine users. Three rhesus monkeys were immunized with a cocaine:bovine serum albumin conjugate in alum and later with complete and incomplete Freund's adjuvants. Monkeys developed cocaine-binding antibodies (as measured by enzyme-linked immunosorbent assay) after immunization with alum; greater antibody titers developed after immunization with Freund's adjuvants. The response rate-decreasing effect of cocaine diminished in proportion to antibody titer; there was no substantial change in the rate-decreasing effect of bupropion. Plasma cocaine concentrations increased in proportion to antibody titer. Immunizations were well tolerated and had no effect on response rates. These data suggest that the antibody response to a cocaine antigen can produce a specific pharmacokinetic shift in cocaine distribution sufficient to antagonize a behavioral effect of the drug, and can do so with minimal side effects.
authors.affiliation: Department of Pharmacology, University of Michigan, Ann Arbor, Michigan 48109-0632, USA.
authors.forename: L
authors.initials: L
authors.lastname: Koetzner
authors.forename: S
authors.initials: S
authors.lastname: Deng
authors.forename: T L
authors.initials: TL
authors.lastname: Sumpter
authors.forename: M
authors.initials: M
authors.lastname: Weisslitz
authors.forename: R T
authors.initials: RT
authors.lastname: Abner
authors.forename: D W
authors.initials: DW
authors.lastname: Landry
authors.forename: J H
authors.initials: JH
authors.lastname: Woods
mesh_terms: D000818:Animals; D000906:Antibodies / Q000097:blood; D001522:Behavior, Animal / Q000187:drug effects; D016642:Bupropion / Q000494:pharmacology; D003042:Cocaine / Q000097:blood / Q000276:immunology* / Q000494:pharmacology; D019970:Cocaine-Related Disorders / Q000517:prevention & control*; D018765:Dopamine Uptake Inhibitors / Q000097:blood / Q000276:immunology / Q000494:pharmacology; D004435:Eating / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005620:Freund's Adjuvant / Q000494:pharmacology; D008253:Macaca mulatta; D008297:Male; D013997:Time Factors; D014611:Vaccination
chemical_list: D000906:Antibodies; D018765:Dopamine Uptake Inhibitors; D016642:Bupropion; D005620:Freund's Adjuvant; D003042:Cocaine