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 ArticleNEUROPHARMACOLOGY

Analysis of Mecamylamine Stereoisomers on Human Nicotinic Receptor Subtypes

Roger L. Papke, Paul R. Sanberg and R. Douglas Shytle
Journal of Pharmacology and Experimental Therapeutics May 2001, 297 (2) 646-656;
Roger L. Papke
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Paul R. Sanberg
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
R. Douglas Shytle
  • 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

Because mecamylamine, a nicotinic receptor antagonist, is used so often in nicotine research and because mecamylamine may have important therapeutic properties clinically, it is important to fully explore and understand its pharmacology. In the present study, the efficacy and potency of mecamylamine and its stereoisomers were evaluated as inhibitors of human α3β4, α3β2, α7, and α4β2 nicotinic acetylcholine receptors (nAChRs), as well as mouse adult type muscle nAChRs and rat N-methyl-d-aspartate (NMDA) receptors expressed in Xenopus oocytes. The selectivity of mecamylamine for neuronal nAChR was manifested primarily in terms of slow recovery rates from mecamylamine-induced inhibition. Neuronal receptors showed a prolonged inhibition after exposure to low micromolar concentrations of mecamylamine. Muscle-type receptors showed a transient inhibition by similar concentrations of mecamylamine, and NMDA receptors were only transiently inhibited by higher micromolar concentrations. Mecamylamine inhibition of neuronal nAChR was noncompetitive and voltage dependent. Although there was little difference between S-(+)-mecamylamine andR-(−)-mecamylamine in terms of 50% inhibition concentration values for a given receptor subtype, there appeared to be significant differences in the off-rates for the mecamylamine isomers from the receptors. Specifically, S-(+)-mecamylamine appeared to dissociate more slowly from α4β2 and α3β4 receptors than did R-(−)-mecamylamine. In addition, it was found that muscle-type receptors appeared to be somewhat more sensitive toR-(−)-mecamylamine than toS-(+)-mecamylamine. Together, these findings suggest that in chronic (i.e., therapeutic) application,S-(+)-mecamylamine might be preferable toR-(−)-mecamylamine in terms of equilibrium inactivation of neuronal receptors with decreased side effects associated with muscle-type receptors.

Footnotes

  • Send reprint requests to: Dr. Roger L. Papke, Associate Professor of Pharmacology and Therapeutics, P.O. Box 100267, 1600 S.W. Archer Rd., University of Florida, College of Medicine, Gainesville, FL 32610. E-mail: rpapke{at}college.med.ufl.edu

  • This study was supported by Layton BioScience, Inc., and the USF I-4 Corridor Program.

  • Abbreviations:
    ACh
    acetylcholine
    nAChR
    nicotinic acetylcholine receptor
    EC10
    EC15, EC30, and EC50, 10%, 15%, 30%, and 50% effective concentrations
    IC50
    50% inhibitory concentration
    NMDA
    N-methyl-d-aspartate
    • Received November 9, 2000.
    • Accepted January 23, 2001.
  • 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: 297 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 297, Issue 2
1 May 2001
  • 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.
Analysis of Mecamylamine Stereoisomers on Human Nicotinic Receptor Subtypes
(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 ArticleNEUROPHARMACOLOGY

Analysis of Mecamylamine Stereoisomers on Human Nicotinic Receptor Subtypes

Roger L. Papke, Paul R. Sanberg and R. Douglas Shytle
Journal of Pharmacology and Experimental Therapeutics May 1, 2001, 297 (2) 646-656;

Citation Manager Formats

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

Share
Research ArticleNEUROPHARMACOLOGY

Analysis of Mecamylamine Stereoisomers on Human Nicotinic Receptor Subtypes

Roger L. Papke, Paul R. Sanberg and R. Douglas Shytle
Journal of Pharmacology and Experimental Therapeutics May 1, 2001, 297 (2) 646-656;
Reddit logo Twitter logo Facebook 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

  • KRM-II-81 Analogs
  • Substituted Tryptamine Activity at 5-HT Receptors and SERT
  • VTA muscarinic M5 receptors and effort-choice behavior
Show more Neuropharmacology

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 © 2023 by the American Society for Pharmacology and Experimental Therapeutics