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.
Footnotes
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Send reprint requests to: James H. Woods, Ph.D., Department of Pharmacology, University of Michigan, 1301 MSRB III, 1150 W. Medical Center Dr., Ann Arbor, MI 48109-0632. E-mail: jhwoods{at}umich.edu
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This study was supported by U.S. Public Health Service Grants DA00254 and DA05777 and a grant from the Office of National Drug Control Policy.
- Abbreviations:
- SRV
- simian retrovirus
- ELISA
- enzyme-linked immunosorbent assay
- CD
- cluster of differentiation protein
- BSA
- bovine serum albumin
- CFA
- complete Freund's adjuvant
- IFA
- incomplete Freund's adjuvant
- HPLC
- high pressure liquid chromatography
- Received May 25, 2000.
- Accepted November 17, 2000.
- The American Society for Pharmacology and Experimental Therapeutics
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