Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • 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
  • 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
  • Log out
  • 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
  • Log out
  • My Cart
Molecular Pharmacology

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • 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
  • Visit molpharm on Facebook
  • Follow molpharm on Twitter
  • Follow molpharm on LinkedIn
Rapid CommunicationAccelerated Communication

BAY36-7620: A Potent Non-Competitive mGlu1 Receptor Antagonist with Inverse Agonist Activity.

Fiona Y. Carroll, Andreas Stolle, Philip M. Beart, Arnd Voerste, Isabelle Brabet, Frank Mauler, Cécile Joly, Horst Antonicek, Joël Bockaert, Thomas Müller, Jean Philippe Pin and Laurent Prézeau
Molecular Pharmacology May 2001, 59 (5) 965-973; DOI: https://doi.org/10.1124/mol.59.5.965
Fiona Y. Carroll
1 2 3
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Andreas Stolle
1 2 3
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Philip M. Beart
1 2 3
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Arnd Voerste
1 2 3
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Isabelle Brabet
1 2 3
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Frank Mauler
1 2 3
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Cécile Joly
1 2 3
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Horst Antonicek
1 2 3
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Joël Bockaert
1 2 3
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Thomas Müller
1 2 3
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jean Philippe Pin
1 2 3
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Laurent Prézeau
1 2 3
  • 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

l-Glutamate (Glu) activates at least eight different G protein-coupled receptors known as metabotropic glutamate (mGlu) receptors, which mostly act as regulators of synaptic transmission. These receptors consist of two domains: an extracellular domain in which agonists bind and a transmembrane heptahelix region involved in G protein activation. Although new mGlu receptor agonists and antagonists have been described, few are selective for a single mGlu subtype. Here, we have examined the effects of a novel compound, BAY36-7620 [(3aS,6aS)- 6a-Naphtalen-2-ylmethyl-5-methyliden-hexahydro-cyclopental[c]furan-1-on], on mGlu receptors (mGlu1–8), transiently expressed in human embryonic kidney 293 cells. BAY36-7620 is a potent (IC50 = 0.16 μM) and selective antagonist at mGlu1 receptors and inhibits >60% of mGlu1a receptor constitutive activity (IC50 = 0.38 μM). BAY36-7620 is therefore the first described mGlu1 receptor inverse agonist. To address the mechanism of action of BAY36-7620, Glu dose-response curves were performed in the presence of increasing concentrations of BAY36-7620. The results show that BAY36-7620 largely decreases the maximal effect of Glu. Moreover, BAY36-7620 did not displace the [3H]quisqualate binding from the Glu-binding pocket, further indicating that BAY36-7620 is a noncompetitive mGlu1 antagonist. Studies of chimeric receptors containing regions of mGlu1 and regions of DmGluA, mGlu2, or mGlu5, revealed that the transmembrane region of mGlu1 is necessary for activity of BAY36-7620. Transmembrane helices 4 to 7 are shown to play a critical role in the selectivity of BAY36-7620. This specific site of action of BAY36-7620 differs from that of competitive antagonists and indicates that the transmembrane region plays a pivotal role in the agonist-independent activity of this receptor. BAY36-7620 will be useful to further delineate the functional importance of the mGlu1 receptor, including its putative agonist-independent activity.

Footnotes

    • Received December 27, 2000.
    • Accepted February 12, 2001.
  • Send reprint requests to: Dr. Laurent Prézeau, Center INSERM-CNRS de Pharmacologie-Endocrinologie - UPR 9023, Laboratoire des Mécanismes Moléculaires des Communications Cellulaires, 141 rue de la Cardonille 34094 Montpellier cedex 5 – France. E-mail:prezeau{at}montp.inserm.fr

  • This work was supported by Grants from the Centre National de la Recherche Scientifique (CNRS; J.B.), Bayer company (France and Germany) (J.B.), the Fondation pour la Recherche Médicale (J.B.), the “Action Incitative Physique et Chimie du Vivant” (PCV00–134) from the CNRS (J.P.P.), the program “Molécules et Cibles Thérapeutiques” from Institut National de la Santé et de la Recherche Médicale (INSERM) and CNRS (J.P.P.), the association Retina France (J.P.P.), by the Australian National Health and Medical Research Council (NH&MRC) Grant (960001) (P. M.B.). F.C. was supported by an INSERM/NH&MRC exchange fellowship (997012).

  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

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: 59 (5)
Molecular Pharmacology
Vol. 59, Issue 5
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 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.
BAY36-7620: A Potent Non-Competitive mGlu1 Receptor Antagonist with Inverse Agonist Activity.
(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
Rapid CommunicationAccelerated Communication

BAY36-7620: A Potent Non-Competitive mGlu1 Receptor Antagonist with Inverse Agonist Activity.

Fiona Y. Carroll, Andreas Stolle, Philip M. Beart, Arnd Voerste, Isabelle Brabet, Frank Mauler, Cécile Joly, Horst Antonicek, Joël Bockaert, Thomas Müller, Jean Philippe Pin and Laurent Prézeau
Molecular Pharmacology May 1, 2001, 59 (5) 965-973; DOI: https://doi.org/10.1124/mol.59.5.965

Citation Manager Formats

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

BAY36-7620: A Potent Non-Competitive mGlu1 Receptor Antagonist with Inverse Agonist Activity.

Fiona Y. Carroll, Andreas Stolle, Philip M. Beart, Arnd Voerste, Isabelle Brabet, Frank Mauler, Cécile Joly, Horst Antonicek, Joël Bockaert, Thomas Müller, Jean Philippe Pin and Laurent Prézeau
Molecular Pharmacology May 1, 2001, 59 (5) 965-973; DOI: https://doi.org/10.1124/mol.59.5.965
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Experimental Procedures
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • GABAA Receptor Desensitization by Low GABA
  • Structure of the Diltiazem Receptor Site on Calcium Channels
  • 5-HT and Sleep
Show more Accelerated Communication

Similar Articles

  • 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 © 2021 by the American Society for Pharmacology and Experimental Therapeutics