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

Antiepileptic and Antiepileptogenic Performance of Carisbamate after Head Injury in the Rat: Blind and Randomized Studies

Clifford L. Eastman, Derek R. Verley, Jason S. Fender, Tessandra H. Stewart, Eytan Nov, Giulia Curia and Raimondo D'Ambrosio
Journal of Pharmacology and Experimental Therapeutics March 2011, 336 (3) 779-790; DOI: https://doi.org/10.1124/jpet.110.175133
Clifford L. Eastman
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Derek R. Verley
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jason S. Fender
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tessandra H. Stewart
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Eytan Nov
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Giulia Curia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Raimondo D'Ambrosio
  • 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

Carisbamate (CRS) exhibits broad acute anticonvulsant activity in conventional anticonvulsant screens, genetic models of absence epilepsy and audiogenic seizures, and chronic spontaneous motor seizures arising after chemoconvulsant-induced status epilepticus. In add-on phase III trials with pharmacoresistant patients CRS induced <30% average decreases in partial-onset seizure frequency. We assessed the antiepileptogenic and antiepileptic performance of subchronic CRS administration on posttraumatic epilepsy (PTE) induced by rostral parasaggital fluid percussion injury (rpFPI), which closely replicates human contusive closed head injury. Studies were blind and randomized, and treatment effects were assessed on the basis of sensitive electrocorticography (ECoG) recordings. Antiepileptogenic effects were assessed in independent groups of control and CRS-treated rats, at 1 and 3 months postinjury, after completion of a 2-week prophylactic treatment initiated 15 min after injury. The antiepileptic effects of 1-week CRS treatments were assessed in repeated measures experiments at 1 and 4 months postinjury. The studies were powered to detect ∼50 and ∼40% decreases in epilepsy incidence and frequency of seizures, respectively. Drug/vehicle treatment, ECoG analysis, and [CRS]plasma determination all were performed blind. We detected no antiepileptogenic and an equivocal transient antiepileptic effects of CRS despite [CRS]plasma comparable with or higher than levels attained in previous preclinical and clinical studies. These findings contrast with previous preclinical data demonstrating large efficacy of CRS, but agree with the average effect of CRS seen in clinical trials. The data support the use of rpFPI-induced PTE in the adolescent rat as a model of pharmacoresistant epilepsy for preclinical development.

Footnotes

  • This work was supported by Johnson and Johnson Pharmaceutical Research and Development, LLC, and the National Institutes of Health National Institute of Neurological Disorders and Stroke [Grant NS053928] (to R.D.).

  • Disclosure: In 2006, R.D. served as a paid consultant to Johnson and Johnson.

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

    doi:10.1124/jpet.110.175133.

  • ABBREVIATIONS:

    CRS
    carisbamate
    AED
    antiepileptic drug
    ECoG
    electrocorticography
    G1
    grade 1
    G2
    grade 2
    G3
    grade 3
    PTE
    posttraumatic epilepsy
    rpFPI
    rostral parasagittal fluid percussion injury
    SE
    status epilepticus.

  • Received September 17, 2010.
  • Accepted November 30, 2010.
  • Copyright © 2011 by 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.
Back to top

In this issue

Journal of Pharmacology and Experimental Therapeutics: 377 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 377, Issue 2
1 May 2021
  • 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.
Antiepileptic and Antiepileptogenic Performance of Carisbamate after Head Injury in the Rat: Blind and Randomized 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

Antiepileptic and Antiepileptogenic Performance of Carisbamate after Head Injury in the Rat: Blind and Randomized Studies

Clifford L. Eastman, Derek R. Verley, Jason S. Fender, Tessandra H. Stewart, Eytan Nov, Giulia Curia and Raimondo D'Ambrosio
Journal of Pharmacology and Experimental Therapeutics March 1, 2011, 336 (3) 779-790; DOI: https://doi.org/10.1124/jpet.110.175133

Citation Manager Formats

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

Antiepileptic and Antiepileptogenic Performance of Carisbamate after Head Injury in the Rat: Blind and Randomized Studies

Clifford L. Eastman, Derek R. Verley, Jason S. Fender, Tessandra H. Stewart, Eytan Nov, Giulia Curia and Raimondo D'Ambrosio
Journal of Pharmacology and Experimental Therapeutics March 1, 2011, 336 (3) 779-790; DOI: https://doi.org/10.1124/jpet.110.175133
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
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Conclusions
    • Authorship Contributions
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • CVN424, a novel GPR6 inverse agonist for Parkinson's disease
  • Methylone Brain Concentrations and Pharmacodynamic Effects
  • Oxysterols and Ethanol
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 © 2021 by the American Society for Pharmacology and Experimental Therapeutics