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
Journal of Pharmacology and Experimental Therapeutics
  • 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
Journal of Pharmacology and Experimental Therapeutics

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 jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
Research ArticleTOXICOLOGY

Cholinesterase Reactivation in Vivo with a Novel Bis-Oxime Optimized by Computer-Aided Design

P. I. Hammond, C. Kern, F. Hong, T. M. Kollmeyer, Y.-P. Pang and S. Brimijoin
Journal of Pharmacology and Experimental Therapeutics October 2003, 307 (1) 190-196; DOI: https://doi.org/10.1124/jpet.103.053405
P. I. Hammond
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
C. Kern
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
F. Hong
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
T. M. Kollmeyer
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Y.-P. Pang
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
S. Brimijoin
  • 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

Recently, several bis-pyridiniumaldoximes linked by a variable-length alkylene chain were rationally designed in our laboratories as cholinesterase reactivators. Extensive in vitro tests of these oximes with acetylcholinesterase inhibited by two different organophosphate agents, echothiophate and diisopropylfluorophosphate, revealed one compound with particularly good reactivation kinetics and affinity for phosphorylated acetylcholinesterase (AChE). This compound, designated “ortho-7”, with a heptylene chain bridging two aldoximes ortho to a pyridinium ring nitrogen, was chosen for detailed comparison with the classic reactivator pyridine-2-aldoxime methochloride (2-PAM). In vitro, ortho-7 reactivated AChE selectively, without restoring activity of the related enzyme butyrylcholinesterase (BChE). For in vivo studies, rats were injected with ortho-7 or 2-PAM before or after organophosphate exposure, and the activities of AChE and BChE were determined at multiple intervals in blood and solid tissues. Ortho-7 behaved nearly as well in the animal as in vitro, reactivating AChE to the same extent as 2-PAM in all peripheral tissues studied (serum, red blood cell, and diaphragm), but at doses up to 100-fold smaller. Like other oxime reactivators, ortho-7 did not reactivate brain AChE after systemic administration. Nonetheless, this agent could be useful in combination therapy for organophosphate exposure, and it may provide a platform for development of additional, even more effective reactivators.

Footnotes

  • DOI: 10.1124/jpet.103.053405.

  • ABBREVIATIONS: OP, organophosphate; AChE, acetylcholinesterase; BChE, butyrylcholinesterase; 2-PAM, pyridine-2-aldoxime methochloride; THA, 9-amino-1,2,3,4-tetrahydroacridine; DFP, diisopropylfluorophosphate; RBC, red blood cell.

    • Received April 23, 2003.
    • Accepted June 5, 2003.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

JPET 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

Journal of Pharmacology and Experimental Therapeutics: 307 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 307, Issue 1
1 Oct 2003
  • 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 Journal of Pharmacology and Experimental Therapeutics 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.
Cholinesterase Reactivation in Vivo with a Novel Bis-Oxime Optimized by Computer-Aided Design
(Your Name) has forwarded a page to you from Journal of Pharmacology and Experimental Therapeutics
(Your Name) thought you would be interested in this article in Journal of Pharmacology and Experimental Therapeutics.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleTOXICOLOGY

Cholinesterase Reactivation in Vivo with a Novel Bis-Oxime Optimized by Computer-Aided Design

P. I. Hammond, C. Kern, F. Hong, T. M. Kollmeyer, Y.-P. Pang and S. Brimijoin
Journal of Pharmacology and Experimental Therapeutics October 1, 2003, 307 (1) 190-196; DOI: https://doi.org/10.1124/jpet.103.053405

Citation Manager Formats

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

Share
Research ArticleTOXICOLOGY

Cholinesterase Reactivation in Vivo with a Novel Bis-Oxime Optimized by Computer-Aided Design

P. I. Hammond, C. Kern, F. Hong, T. M. Kollmeyer, Y.-P. Pang and S. Brimijoin
Journal of Pharmacology and Experimental Therapeutics October 1, 2003, 307 (1) 190-196; DOI: https://doi.org/10.1124/jpet.103.053405
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
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Nafamostat is a potent human diamine oxidase inhibitor
  • Chemoproteomics Investigation of Testicular Toxicity with BTK Inhibitor
  • Bosentan Alters Bile Salt Disposition
Show more Toxicology

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

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0103 (Online)

Copyright © 2022 by the American Society for Pharmacology and Experimental Therapeutics