Skip to main content

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • For Subscribers
    • For Advertisers
    • 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

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
Journal of Pharmacology and Experimental Therapeutics

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • For Subscribers
    • For Advertisers
    • 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 ArticleMetabolism, Transport, and Pharmacogenomics

Studies of (±)-3,4-Methylenedioxymethamphetamine (MDMA) Metabolism and Disposition in Rats and Mice: Relationship to Neuroprotection and Neurotoxicity Profile

Melanie Mueller, Concepcion Maldonado-Adrian, Jie Yuan, Una D. McCann and George A. Ricaurte
Journal of Pharmacology and Experimental Therapeutics February 2013, 344 (2) 479-488; DOI: https://doi.org/10.1124/jpet.112.201699
Melanie Mueller
Departments of Neurology (M.M., C.M.-A., J.Y., G.A.R.) and Psychiatry (U.D.M.), Johns Hopkins University School of Medicine, Baltimore, Maryland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Concepcion Maldonado-Adrian
Departments of Neurology (M.M., C.M.-A., J.Y., G.A.R.) and Psychiatry (U.D.M.), Johns Hopkins University School of Medicine, Baltimore, Maryland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jie Yuan
Departments of Neurology (M.M., C.M.-A., J.Y., G.A.R.) and Psychiatry (U.D.M.), Johns Hopkins University School of Medicine, Baltimore, Maryland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Una D. McCann
Departments of Neurology (M.M., C.M.-A., J.Y., G.A.R.) and Psychiatry (U.D.M.), Johns Hopkins University School of Medicine, Baltimore, Maryland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
George A. Ricaurte
Departments of Neurology (M.M., C.M.-A., J.Y., G.A.R.) and Psychiatry (U.D.M.), Johns Hopkins University School of Medicine, Baltimore, Maryland
  • 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

The neurotoxicity of (±)-3,4-methylenedioxymethamphetamine (MDMA; “Ecstasy”) is influenced by temperature and varies according to species. The mechanisms underlying these two features of MDMA neurotoxicity are unknown, but differences in MDMA metabolism have recently been implicated in both. The present study was designed to 1) assess the effect of hypothermia on MDMA metabolism, 2) determine whether the neuroprotective effect of hypothermia is related to inhibition of MDMA metabolism, and 3) determine if different neurotoxicity profiles in mice and rats are related to differences in MDMA metabolism and/or disposition in the two species. Rats and mice received single neurotoxic oral doses of MDMA at 25°C and 4°C, and body temperature, pharmacokinetic parameters, and serotonergic and dopaminergic neuronal markers were measured. Hypothermia did not alter MDMA metabolism in rats and only modestly inhibited MDMA metabolism in mice; however, it afforded complete neuroprotection in both species. Rats and mice metabolized MDMA in a similar pattern, with 3,4-methylenedioxyamphetamine being the major metabolite, followed by 4-hydroxy-3-methoxymethamphetamine and 3,4-dihydroxymethamphetamine, respectively. Differences between MDMA pharmacokinetics in rats and mice, including faster elimination in mice, did not account for the different profile of MDMA neurotoxicity in the two species. Taken together, the results of these studies indicate that inhibition of MDMA metabolism is not responsible for the neuroprotective effect of hypothermia in rodents, and that different neurotoxicity profiles in rats and mice are not readily explained by differences in MDMA metabolism or disposition.

Footnotes

  • This work was supported by the National Institutes of Health National Institute on Drug Abuse [Grants DA05707 and DA01796401].

  • dx.doi.org/10.1124/jpet.112.201699.

  • Received November 5, 2012.
  • Accepted November 29, 2012.
  • Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics
View Full Text

Log in using your username and password

Forgot your user name or password?

Pay Per Article - You may access this article (from the computer you are currently using) for 1 day for US$35.00

Regain Access - You can regain access to a recent Pay per Article purchase if your access period has not yet expired.

PreviousNext
Back to top

In this issue

Journal of Pharmacology and Experimental Therapeutics: 344 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 344, Issue 2
1 Feb 2013
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • 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 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.
Studies of (±)-3,4-Methylenedioxymethamphetamine (MDMA) Metabolism and Disposition in Rats and Mice: Relationship to Neuroprotection and Neurotoxicity Profile
(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.
Citation Tools
Research ArticleMetabolism, Transport, and Pharmacogenomics

MDMA Pharmacokinetics and Neurotoxicity in Rodents

Melanie Mueller, Concepcion Maldonado-Adrian, Jie Yuan, Una D. McCann and George A. Ricaurte
Journal of Pharmacology and Experimental Therapeutics February 1, 2013, 344 (2) 479-488; DOI: https://doi.org/10.1124/jpet.112.201699

Citation Manager Formats

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

Share
Research ArticleMetabolism, Transport, and Pharmacogenomics

MDMA Pharmacokinetics and Neurotoxicity in Rodents

Melanie Mueller, Concepcion Maldonado-Adrian, Jie Yuan, Una D. McCann and George A. Ricaurte
Journal of Pharmacology and Experimental Therapeutics February 1, 2013, 344 (2) 479-488; DOI: https://doi.org/10.1124/jpet.112.201699
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
    • Authorship Contributions
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Whole-Body PK and PBPK Model for T cells
  • Brain Delivery of panRAF Inhibitors
  • Regulation of P450s by HNF1α and HNF1α-AS1
Show more Metabolism, Transport, and Pharmacogenomics

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 © 2019 by the American Society for Pharmacology and Experimental Therapeutics