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Research ArticleNEUROPHARMACOLOGY

Treatment of Adverse Effects of Excessive Phencyclidine Exposure in Rats with a Minimal Dose of Monoclonal Antibody

Elizabeth M. Laurenzana, Melinda G. Gunnell, W. Brooks Gentry and S. Michael Owens
Journal of Pharmacology and Experimental Therapeutics September 2003, 306 (3) 1092-1098; DOI: https://doi.org/10.1124/jpet.103.053140
Elizabeth M. Laurenzana
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Melinda G. Gunnell
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W. Brooks Gentry
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S. Michael Owens
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Abstract

The range of medical effects and complications resulting from excessive use of drugs of abuse like phencyclidine (PCP) has hindered the development of effective medications. Drug-specific monoclonal antibodies (mAbs) provide an appealing medication approach since they can be selective for the drug, without concern for the sites of action of the drug. The use of mAb medications has been considered impractical because it is commonly believed that very large doses of mAb would be required to treat the adverse medical effects resulting from excessive drug use. In this study, a single dose of an anti-PCP mAb was found to significantly reduce the negative health impact of excessive, prolonged PCP treatment in rats (18 mg/kg/day for 2 weeks). The protective effects were mAb dose-dependent, and mAb doses as low as 1/100th the molar equivalent amount of the PCP body burden were effective at preventing PCP-induced deaths, reducing PCP-induced behaviors, reducing PCP brain concentrations, and improving the general health status of the animals. They also show that treatment with monoclonal antibody medications can have medically important outcomes without the need to neutralize the entire dose of the offending drug. These results could help establish the feasibility of using carefully designed monoclonal antibody medications to treat drug abuse and addiction, a chronic and re-occurring illness of the central nervous system.

Footnotes

  • This work was supported by National Institute on Drug Abuse Grants DA 07610 to S. M. Owens and K08 DA0339 to W. B. Gentry.

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

  • DOI: 10.1124/jpet.103.053140.

  • ABBREVIATIONS: PCP, phencyclidine; mAb, monoclonal antibody; t1/2λz, terminal elimination half-life; ANOVA, analysis of variance.

    • Received April 16, 2003.
    • Accepted June 5, 2003.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 306 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 306, Issue 3
1 Sep 2003
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Research ArticleNEUROPHARMACOLOGY

Treatment of Adverse Effects of Excessive Phencyclidine Exposure in Rats with a Minimal Dose of Monoclonal Antibody

Elizabeth M. Laurenzana, Melinda G. Gunnell, W. Brooks Gentry and S. Michael Owens
Journal of Pharmacology and Experimental Therapeutics September 1, 2003, 306 (3) 1092-1098; DOI: https://doi.org/10.1124/jpet.103.053140

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Research ArticleNEUROPHARMACOLOGY

Treatment of Adverse Effects of Excessive Phencyclidine Exposure in Rats with a Minimal Dose of Monoclonal Antibody

Elizabeth M. Laurenzana, Melinda G. Gunnell, W. Brooks Gentry and S. Michael Owens
Journal of Pharmacology and Experimental Therapeutics September 1, 2003, 306 (3) 1092-1098; DOI: https://doi.org/10.1124/jpet.103.053140
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