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
Molecular Pharmacology
  • 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
Molecular Pharmacology

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 molpharm on Facebook
  • Follow molpharm on Twitter
  • Follow molpharm on LinkedIn
Research ArticleArticle

Kinetic Effects of Leptocurares and Pachycurares on the Methanesulfonylation of Acetylcholinesterase

A Correlation with Pharmacodynamic Properties

B. BELLEAU, V. DITULLIO and Y.-H. TSAI
Molecular Pharmacology January 1970, 6 (1) 41-45;
B. BELLEAU
Departments of Chemistry and Biochemistry, University of Ottawa, Ottawa 2, Ontario, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
V. DITULLIO
Departments of Chemistry and Biochemistry, University of Ottawa, Ottawa 2, Ontario, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Y.-H. TSAI
Departments of Chemistry and Biochemistry, University of Ottawa, Ottawa 2, Ontario, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

It was shown previously that the alkyltrimethylammonium ion series of cholinergicl and anticholinergic drugs not only fail to protect acetylcholinesterase (AChE) against irreversible esterification by methanesulfonyl fluoride of its active serine hydroxyl, but actually accelerate the reaction, thus showing that the alkyl chains do not bind bind on the catalytic esteratic sites themselves (exo orientation). Acceleration has been explain in terms of conformational perturbations, and maximum potency in this regard was exhibited by the n-hexyl membber, followed by a sharp reversal of the acceleration trend at the n-heptyl member. Parallel trends and shifts in potencies at the receptor level are well documented. Using the same experimental techniques, it has now been found that leptocurares (polymethoniums of the decamethonium series, including succinylcholine) also behave as accelerators of the methanesulfonylation reaction, peak activity being observed with decamethonium. Succinylcholine was 4 times more active than the latter in stimulating the methanesulfonylation reaction. The trend in stimulating potencies closely parallels the relative blocking potencies at the motor end plate level. In marked contrast, d-tubocurarine and gallamine protect AChE against methanesulfonyl fluoride by a mechanism which does not obey the laws of competitive kinetics. The application of conventional assay techniques had previously led to the conclusion that pachycurares are competitive inhibitors of the cationic substrate ACh at both the enzyme and myoneural junction levels. However, evidence that the inhibition is rather of the partially competitive type has recently been reported. Since the methanesulfonyl fluoride molecule, unlike ACh, carries no charge, it can hardly compete directly with pachycurares for charged binding sites. Hence, the observed partially competitive relationship must be the result of pachycurare-induced change transmitted to the esteratic center from outer anionic sites. These contrasting properties of leptocurares and pachycurares as modifiers of conformation find an exact parallel in the divergence of their mechanisms of blockade at the myoneural junction level. These observations furnish new insight into the interaction topographies underlying the ligand-induced conformational changes.

  • Copyright ©, 1970, by Academic Press Inc.

MolPharm 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

Molecular Pharmacology
Vol. 6, Issue 1
1 Jan 1970
  • Table of Contents
  • Table of Contents (PDF)
  • Index by author
  • Editorial Board (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Molecular Pharmacology 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.
Kinetic Effects of Leptocurares and Pachycurares on the Methanesulfonylation of Acetylcholinesterase
(Your Name) has forwarded a page to you from Molecular Pharmacology
(Your Name) thought you would be interested in this article in Molecular Pharmacology.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

Kinetic Effects of Leptocurares and Pachycurares on the Methanesulfonylation of Acetylcholinesterase

B. BELLEAU, V. DITULLIO and Y.-H. TSAI
Molecular Pharmacology January 1, 1970, 6 (1) 41-45;

Citation Manager Formats

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

Share
Research ArticleArticle

Kinetic Effects of Leptocurares and Pachycurares on the Methanesulfonylation of Acetylcholinesterase

B. BELLEAU, V. DITULLIO and Y.-H. TSAI
Molecular Pharmacology January 1, 1970, 6 (1) 41-45;
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
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Effects of Small Molecule Ligands on ACKR3 Receptors
  • Michaelis-Menten Quantification of GPCR-G Protein Signaling
  • Anti-aromatase activity of exemestane phase II metabolites
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 Molecular Pharmacology
  • 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
  • Journal of Pharmacology and Experimental Therapeutics
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0111 (Online)

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