QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.103.053140v1 306/3/1092    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Laurenzana, E. M. Articles by Owens, S. M. Search for Related Content PubMed PubMed Citation Articles by Laurenzana, E. M. Articles by Owens, S. M. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB PHENCYCLIDINE

NEUROPHARMACOLOGY

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

Departments of Pharmacology and Toxicology (E.M.L., M.G.G., W.B.G., S.M.O.), and Anesthesiology (W.B.G.), College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas

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.

Address correspondence to: Dr. S. Michael Owens, Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, 4301 West Markham Street, Slot 611, Little Rock, AR 72205. E-mail: owenssamuelm{at}uams.edu

This article has been cited by other articles:

				G. Pitas, E. M. Laurenzana, D. K. Williams, S. M. Owens, and W. B. Gentry ANTI-PHENCYCLIDINE MONOCLONAL ANTIBODY BINDING CAPACITY IS NOT THE ONLY DETERMINANT OF EFFECTIVENESS, DISPROVING THE CONCEPT THAT ANTIBODY CAPACITY IS EASILY SURMOUNTED Drug Metab. Dispos., June 1, 2006; 34(6): 906 - 912. [Abstract] [Full Text] [PDF]

				P. R. Pentel, M. B. Dufek, S. A. Roiko, M. G. LeSage, and D. E. Keyler Differential Effects of Passive Immunization with Nicotine-Specific Antibodies on the Acute and Chronic Distribution of Nicotine to Brain in Rats J. Pharmacol. Exp. Ther., May 1, 2006; 317(2): 660 - 666. [Abstract] [Full Text] [PDF]

				D. E. Keyler, S. A. Roiko, E. Benlhabib, M. G. LeSage, J. V. St. Peter, S. Stewart, S. Fuller, C. T. Le, and P. R. Pentel MONOCLONAL NICOTINE-SPECIFIC ANTIBODIES REDUCE NICOTINE DISTRIBUTION TO BRAIN IN RATS: DOSE- AND AFFINITY-RESPONSE RELATIONSHIPS Drug Metab. Dispos., July 1, 2005; 33(7): 1056 - 1061. [Abstract] [Full Text] [PDF]