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
Abstract

Enantioselectivity of steroid-induced gamma-aminobutyric acidA receptor modulation and anesthesia.

L L Wittmer, Y Hu, M Kalkbrenner, A S Evers, C F Zorumski and D F Covey
Molecular Pharmacology December 1996, 50 (6) 1581-1586;
L L Wittmer
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Y Hu
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
M Kalkbrenner
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
A S Evers
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
C F Zorumski
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
D F Covey
  • 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

Neuroactive steroids have been postulated to cause anesthesia by binding to unique steroid recognition sites on gamma-aminobutyric acid (GABA) receptors and modulating GABA receptor function. Steroids interact with these sites diastereoselectively, but it is unknown whether steroid sites show enantioselectivity. To address this issue, we synthesized enantiomers to (+)-3alpha-hydroxy-5alpha-androstane-17beta-carbonitrile and (+)-3alpha-hydroxy-5alpha-pregnan-20-one. In this study, we show that potentiation of GABA-mediated currents and gating of the GABA(A) channel by steroids, as well as steroid-induced anesthesia in tadpoles and mice, is enantioselective, with the (+)-enantiomers exhibiting significantly greater potency in all assays. The correlation between the effects of steroid enantiomers on channel behavior and their effects as anesthetics provides strong evidence that GABA(A) receptors play a predominant role in steroid-induced anesthesia. The enantiomers also provide a tool to probe the relative contributions of direct chloride channel activation versus potentiation of GABA-elicited currents to the induction of anesthesia. Studies examining the effects of combinations of (+)- and (-)-3alpha-hydroxy-5alpha-androstane-17beta-carbonitrile were consistent with the hypothesis that potentiation of GABA-activated currents contributes to steroid-induced anesthesia but indicated that direct steroid activation of GABA(A) receptors is not mechanistically important in producing anesthesia.

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. 50, Issue 6
1 Dec 1996
  • Table of Contents
  • Table of Contents (PDF)
  • Index by author
  • Back Matter (PDF)
  • Editorial Board (PDF)
  • Front Matter (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.
Enantioselectivity of steroid-induced gamma-aminobutyric acidA receptor modulation and anesthesia.
(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
Abstract

Enantioselectivity of steroid-induced gamma-aminobutyric acidA receptor modulation and anesthesia.

L L Wittmer, Y Hu, M Kalkbrenner, A S Evers, C F Zorumski and D F Covey
Molecular Pharmacology December 1, 1996, 50 (6) 1581-1586;

Citation Manager Formats

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

Share
Abstract

Enantioselectivity of steroid-induced gamma-aminobutyric acidA receptor modulation and anesthesia.

L L Wittmer, Y Hu, M Kalkbrenner, A S Evers, C F Zorumski and D F Covey
Molecular Pharmacology December 1, 1996, 50 (6) 1581-1586;
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...

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