Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Drug Metabolism & Disposition
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Drug Metabolism & Disposition

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit dmd on Facebook
  • Follow dmd on Twitter
  • Follow ASPET on LinkedIn
Research ArticleArticle

MONOCLONAL NICOTINE-SPECIFIC ANTIBODIES REDUCE NICOTINE DISTRIBUTION TO BRAIN IN RATS: DOSE- AND AFFINITY-RESPONSE RELATIONSHIPS

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
Drug Metabolism and Disposition July 2005, 33 (7) 1056-1061; DOI: https://doi.org/10.1124/dmd.105.004234
D. E. Keyler
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
S. A. Roiko
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
E. Benlhabib
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
M. G. LeSage
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
J. V. St. Peter
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
S. Stewart
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
S. Fuller
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
C. T. Le
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
P. R. Pentel
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

Vaccination against nicotine is being studied as a potential treatment for nicotine dependence. Some of the limitations of vaccination, such as variability in antibody titer and affinity, might be overcome by instead using passive immunization with nicotine-specific monoclonal antibodies. The effects of antibodies on nicotine distribution to brain were studied using nicotine-specific monoclonal antibodies (NICmAbs) with Kd values ranging from 60 to 250 nM and a high-affinity polyclonal rabbit antiserum (Kd = 1.6 nM). Pretreatment with NICmAbs substantially increased the binding of nicotine in serum after a single nicotine dose, reduced the unbound nicotine concentration in serum, and reduced the distribution of nicotine to brain. Efficacy was directly related to antibody affinity for nicotine. Efficacy of the highest affinity NICmAb, NICmAb311, was dose-related, with the highest dose reducing nicotine distribution to brain by 78%. NICmAb311 decreased nicotine clearance by 90% and prolonged the terminal half-life of nicotine by 120%. At equivalent doses, NICmAb311 was less effective than the higher affinity rabbit antiserum but comparable efficacy could be achieved by increasing the NICmAb311 dose. These data suggest that passive immunization with nicotine-specific monoclonal antibodies substantially alters nicotine pharmacokinetics in a manner similar to that previously reported for vaccination against nicotine. Antibody efficacy is a function of both dose and affinity for nicotine.

Footnotes

  • This study was supported by Public Health Service Grants DA10714, P50-DA13333, and T32-DA07097.

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

  • doi:10.1124/dmd.105.004234.

  • ABBREVIATIONS: NICmAb, monoclonal anti-nicotine antibody; mAb, monoclonal antibody; Nic-IgG, polyclonal rabbit anti-nicotine antiserum; PBS, phosphate-buffered saline; ELISA, enzyme-linked immunosorbent assay; AUC, area under the concentration-time curve; Clt, total clearance.

    • Received February 18, 2005.
    • Accepted April 15, 2005.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

 

DMD articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Drug Metabolism and Disposition: 33 (7)
Drug Metabolism and Disposition
Vol. 33, Issue 7
1 Jul 2005
  • Table of Contents
  • About the Cover
  • Index by author
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Drug Metabolism & Disposition article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
MONOCLONAL NICOTINE-SPECIFIC ANTIBODIES REDUCE NICOTINE DISTRIBUTION TO BRAIN IN RATS: DOSE- AND AFFINITY-RESPONSE RELATIONSHIPS
(Your Name) has forwarded a page to you from Drug Metabolism & Disposition
(Your Name) thought you would be interested in this article in Drug Metabolism & Disposition.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

MONOCLONAL NICOTINE-SPECIFIC ANTIBODIES REDUCE NICOTINE DISTRIBUTION TO BRAIN IN RATS: DOSE- AND AFFINITY-RESPONSE RELATIONSHIPS

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
Drug Metabolism and Disposition July 1, 2005, 33 (7) 1056-1061; DOI: https://doi.org/10.1124/dmd.105.004234

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Research ArticleArticle

MONOCLONAL NICOTINE-SPECIFIC ANTIBODIES REDUCE NICOTINE DISTRIBUTION TO BRAIN IN RATS: DOSE- AND AFFINITY-RESPONSE RELATIONSHIPS

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
Drug Metabolism and Disposition July 1, 2005, 33 (7) 1056-1061; DOI: https://doi.org/10.1124/dmd.105.004234
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Identification of payload-containing catabolites of ADCs
  • PK Interactions of Licorice with Cytochrome P450s
  • Biotransformation of Trastuzumab and Pertuzumab
Show more Articles

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About DMD
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Journal of Pharmacology and Experimental Therapeutics
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-009X (Online)

Copyright © 2023 by the American Society for Pharmacology and Experimental Therapeutics