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

Neuroprotective Efficacy and Therapeutic Window of the High-Affinity N-Methyl-d-aspartate Antagonist Conantokin-G: In Vitro (Primary Cerebellar Neurons) and In Vivo (Rat Model of Transient Focal Brain Ischemia) Studies

Anthony J. Williams, Jitendra R. Dave, James B. Phillips, Yu Lin, R. Tyler McCabe and Frank C. Tortella
Journal of Pharmacology and Experimental Therapeutics July 2000, 294 (1) 378-386;
Anthony J. Williams
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jitendra R. Dave
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
James B. Phillips
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yu Lin
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
R. Tyler McCabe
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Frank C. Tortella
  • 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

Conantokin-G (Con-G), a 17-amino-acid peptide derived from marine snails and a potent N-methyl-d-aspartate (NMDA) antagonist, was evaluated for its neuroprotective properties in vitro and in vivo. In primary cerebellar neurons, Con-G was shown to decrease excitotoxic calcium responses to NMDA and to exhibit differential neuroprotection potencies against hypoxia/hypoglycemia-, NMDA-, glutamate-, or veratridine-induced injury. Using the intraluminal filament method of middle cerebral artery occlusion as an in vivo rat model of transient focal brain ischemia, the neuroprotective dose-response effect of Con-G administration beginning 30 min postocclusion was evaluated after 2 h of ischemia and 22 h of reperfusion. In the core region of injury, an 89% reduction in brain infarction was measured with significant neurological and electroencephalographic recovery at the maximal dose tested (2 nmol), although mild sedation was noted. Lower doses of Con-G (0.001–0.5 nmol) were significantly neuroprotective without causing sedation. Postinjury time course experiments demonstrated a therapeutic window out to at least 4 to 8 h from the start of the injury, providing a 47% reduction in core injury. The neuroprotective effect of Con-G (0.5 nmol) was also evaluated after 72 h of injury, where a 54% reduction in core brain infarction was measured. Critically, in both recovery models (i.e., 24 and 72 h), the reduction in brain infarction was associated with significant improvements in neurological and electroencephalographic recovery. These data provide evidence for the potent and highly efficacious effect of Con-G as a neuroprotective agent, with an excellent therapeutic window for the potential intervention against ischemic/excitotoxic brain injury.

Footnotes

  • Send reprint requests to: Dr. Frank C. Tortella, Department of Neuropharmacology & Molecular Biology, Division of Neurosciences, Walter Reed Army Institute of Research, Bldg. 503, Forney Dr., Forest Glen Annex, Silver Spring, MD 20910. E-mail:Frank.Tortella{at}na.amedd.army.mil

  • ↵1 The views of the authors do not purport or reflect the position of the Department of the Army or the Department of Defense (para 4-3, AR 360-5). This work was supported in part by Cognetix, Inc. and funds from DOD/U.S. Army. Preliminary versions of this data were published in abstract form in SocNeurosci Abstr (1998) 24(1):978 and FASEB Abstr (1999) 13(5):A1099.

  • Abbreviations:
    NMDA
    N-methyl-d-aspartate
    MCAo
    middle cerebral artery occlusion
    EEG
    electroencephalogram
    Con-G
    conantokin-G
    TTC
    2,3,5-triphenyltetrazolium chloride
    H/H
    hypoxia/hypoglycemia
    MABP
    mean arterial blood pressure
    HR
    heart rate
    MTT
    3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
    [Ca2+]i
    intraneuronal calcium concentration
    • Received December 9, 1999.
    • Accepted March 10, 2000.
  • U.S. Government
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: 294 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 294, Issue 1
1 Jul 2000
  • 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.
Neuroprotective Efficacy and Therapeutic Window of the High-Affinity N-Methyl-d-aspartate Antagonist Conantokin-G: In Vitro (Primary Cerebellar Neurons) and In Vivo (Rat Model of Transient Focal Brain Ischemia) Studies
(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

Neuroprotective Efficacy and Therapeutic Window of the High-Affinity N-Methyl-d-aspartate Antagonist Conantokin-G: In Vitro (Primary Cerebellar Neurons) and In Vivo (Rat Model of Transient Focal Brain Ischemia) Studies

Anthony J. Williams, Jitendra R. Dave, James B. Phillips, Yu Lin, R. Tyler McCabe and Frank C. Tortella
Journal of Pharmacology and Experimental Therapeutics July 1, 2000, 294 (1) 378-386;

Citation Manager Formats

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

Neuroprotective Efficacy and Therapeutic Window of the High-Affinity N-Methyl-d-aspartate Antagonist Conantokin-G: In Vitro (Primary Cerebellar Neurons) and In Vivo (Rat Model of Transient Focal Brain Ischemia) Studies

Anthony J. Williams, Jitendra R. Dave, James B. Phillips, Yu Lin, R. Tyler McCabe and Frank C. Tortella
Journal of Pharmacology and Experimental Therapeutics July 1, 2000, 294 (1) 378-386;
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
    • Materials and Methods
    • Results
    • Discussion
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Oxysterols and ethanol
  • P-glycoprotein Apical Efflux Ratio for Compound Optimization
  • Pharmacology of Carbamate Insecticides at MT1 & MT2
Show more Neuropharmacology

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 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 © 2021 by the American Society for Pharmacology and Experimental Therapeutics