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Research ArticleNEUROPHARMACOLOGY

Titer-Dependent Antagonism of Cocaine following Active Immunization in Rhesus Monkeys

Lee Koetzner, Shixian Deng, Tina L. Sumpter, Michael Weisslitz, Ronald T. Abner, Donald W. Landry and James H. Woods
Journal of Pharmacology and Experimental Therapeutics March 2001, 296 (3) 789-796;
Lee Koetzner
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Shixian Deng
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Tina L. Sumpter
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Michael Weisslitz
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Ronald T. Abner
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Donald W. Landry
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James H. Woods
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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

  • 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

  • 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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Journal of Pharmacology and Experimental Therapeutics: 296 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 296, Issue 3
1 Mar 2001
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Research ArticleNEUROPHARMACOLOGY

Titer-Dependent Antagonism of Cocaine following Active Immunization in Rhesus Monkeys

Lee Koetzner, Shixian Deng, Tina L. Sumpter, Michael Weisslitz, Ronald T. Abner, Donald W. Landry and James H. Woods
Journal of Pharmacology and Experimental Therapeutics March 1, 2001, 296 (3) 789-796;

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Research ArticleNEUROPHARMACOLOGY

Titer-Dependent Antagonism of Cocaine following Active Immunization in Rhesus Monkeys

Lee Koetzner, Shixian Deng, Tina L. Sumpter, Michael Weisslitz, Ronald T. Abner, Donald W. Landry and James H. Woods
Journal of Pharmacology and Experimental Therapeutics March 1, 2001, 296 (3) 789-796;
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