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
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
    • 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 jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
Research ArticleBEHAVIORAL PHARMACOLOGY

SL25.1131 [3(S),3a(S)-3-Methoxymethyl-7-[4,4,4-trifluorobutoxy]-3,3a,4,5-tetrahydro-1,3-oxazolo[3,4-a]quinolin-1-one], a New, Reversible, and Mixed Inhibitor of Monoamine Oxidase-A and Monoamine Oxidase-B: Biochemical and Behavioral Profile

N. Aubin, P. Barneoud, C. Carter, D. Caille, N. Sontag, C. Marc, J. Lolivier, A. Gardes, C. Perron, A. Le Kim, T. Charieras, M. Pandini, P. Burnier, F. Puech, S. Jegham, P. George, B. Scatton and O. Curet
Journal of Pharmacology and Experimental Therapeutics September 2004, 310 (3) 1171-1182; DOI: https://doi.org/10.1124/jpet.103.064782
N. Aubin
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
P. Barneoud
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
C. Carter
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
D. Caille
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
N. Sontag
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
C. Marc
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
J. Lolivier
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
A. Gardes
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
C. Perron
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
A. Le Kim
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
T. Charieras
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
M. Pandini
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
P. Burnier
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
F. Puech
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
S. Jegham
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
P. George
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
B. Scatton
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
O. Curet
  • 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

SL25.1131 [3(S),3a(S)-3-methoxymethyl-7-[4,4,4-trifluorobutoxy]-3,3a,4,5-tetrahydro-1,3-oxazolo[3,4-a]quinolin-1-one] is a new, nonselective, and reversible monoamine oxidase (MAO) inhibitor, belonging to a oxazoloquinolinone series. In vitro studies showed that SL25.1131 inhibits rat brain MAO-A and MAO-B with IC50 values of 6.7 and 16.8 nM and substrate-dependent Ki values of 3.3 and 4.2 nM, respectively. In ex vivo conditions, the oral administration of SL25.1131 induced a dose-dependent inhibition of MAO-A and MAO-B activities in the rat brain with ED50 values of 0.67 and 0.52 mg/kg, respectively. In the rat brain, duodenum, and liver, the inhibition of MAO-A and MAO-B by SL25.1131 (3.5 mg/kg p.o.) was reversible, and the recovery of MAO-A and MAO-B activities was complete 16 h after administration. SL25.1131 (3.5 mg/kg p.o.) increased tissue levels of dopamine (DA), norepinephrine, and 5-hydroxytryptamine and decreased levels of their deaminated metabolites 3,4-dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindolacetic acid. In mice, SL25.1131 induced a dose-dependent potentiation of 5-hydroxytryptophan-induced tremors and phenylethylamine-induced stereotypies with ED50 values of 0.60 and 2.8 mg/kg p.o., respectively. SL25.1131 was able to reestablish normal striatal dopaminergic tone and locomotor activity in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mice. In addition, when coadministered with l-DOPA, SL25.1131 increased the available DA in the striatum and the duration of l-DOPA-induced hyperactivity. The duration of the effect of l-DOPA on circling behavior in 6-hydroxydopamine-lesioned rats was also increased. The neurochemical profile of SL25.1131 demonstrates that this compound is a mixed, potent, and reversible MAO-A/B inhibitor in vitro, in vivo, and ex vivo. SL25.1131 has therapeutic potential as a symptomatic treatment during the early phase of Parkinson's disease and as an adjunct tol-DOPA therapy during the early and late phases of the disease.

Footnotes

  • doi:10.1124/jpet.103.064782.

  • ABBREVIATIONS: MAO, monoamine oxidase; 5-HT, 5-hydroxytryptamine (serotonin); NE, norepinephrine; PEA, phenylethylamine; DA, dopamine; TYR, tyramine; PD, Parkinson's disease; l-5-HTP, l-5-hydroxytryptophan; MPTP, 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine; DOPAC, 3,4-dihydroxyphenylacetic acid; HVA, homovanillic acid; 3-MT, 3-methoxytyramine; NMN, normetanephrine; 5-HIAA, 5-hydroxyindolacetic acid; DHBA, 3,4-dihydroxybenzylamine; 6-OHDA, 6-hydroxydopamine; Kiapp; substrate-dependent Ki; MAOI, monoamine oxidase inhibitor; SBP, systolic blood pressure; COMT, catechol-O-methyl-transferase; SL25.1131, 3(S),3a(S)-3-methoxymethyl-7-[4,4,4-trifluorobutoxy]3,3a,4,5-tetrahydro-1,3-oxazolo[3,4-a]quinolin-1-one; BW137OU87, 1-ethylphenoxathiin-10,10-dioxide; GBR12935, 1-[2-(disphenyl-methoxy)ethyl]-4-(3-phenylpropyl) piperazine; Ro41-1049, N-(2-aminoethyl)-5-(3-fluorophenyl) thiazole-4-carboxamide hydrochloride; Ro19-6327, lazabemide.

    • Received December 22, 2003.
    • Accepted May 17, 2004.
  • 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.
PreviousNext
Back to top

In this issue

Journal of Pharmacology and Experimental Therapeutics: 310 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 310, Issue 3
1 Sep 2004
  • 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.
SL25.1131 [3(S),3a(S)-3-Methoxymethyl-7-[4,4,4-trifluorobutoxy]-3,3a,4,5-tetrahydro-1,3-oxazolo[3,4-a]quinolin-1-one], a New, Reversible, and Mixed Inhibitor of Monoamine Oxidase-A and Monoamine Oxidase-B: Biochemical and Behavioral 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.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleBEHAVIORAL PHARMACOLOGY

SL25.1131 [3(S),3a(S)-3-Methoxymethyl-7-[4,4,4-trifluorobutoxy]-3,3a,4,5-tetrahydro-1,3-oxazolo[3,4-a]quinolin-1-one], a New, Reversible, and Mixed Inhibitor of Monoamine Oxidase-A and Monoamine Oxidase-B: Biochemical and Behavioral Profile

N. Aubin, P. Barneoud, C. Carter, D. Caille, N. Sontag, C. Marc, J. Lolivier, A. Gardes, C. Perron, A. Le Kim, T. Charieras, M. Pandini, P. Burnier, F. Puech, S. Jegham, P. George, B. Scatton and O. Curet
Journal of Pharmacology and Experimental Therapeutics September 1, 2004, 310 (3) 1171-1182; DOI: https://doi.org/10.1124/jpet.103.064782

Citation Manager Formats

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

Share
Research ArticleBEHAVIORAL PHARMACOLOGY

SL25.1131 [3(S),3a(S)-3-Methoxymethyl-7-[4,4,4-trifluorobutoxy]-3,3a,4,5-tetrahydro-1,3-oxazolo[3,4-a]quinolin-1-one], a New, Reversible, and Mixed Inhibitor of Monoamine Oxidase-A and Monoamine Oxidase-B: Biochemical and Behavioral Profile

N. Aubin, P. Barneoud, C. Carter, D. Caille, N. Sontag, C. Marc, J. Lolivier, A. Gardes, C. Perron, A. Le Kim, T. Charieras, M. Pandini, P. Burnier, F. Puech, S. Jegham, P. George, B. Scatton and O. Curet
Journal of Pharmacology and Experimental Therapeutics September 1, 2004, 310 (3) 1171-1182; DOI: https://doi.org/10.1124/jpet.103.064782
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
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Role of residues S426 and S430 in cannabinoid tolerance
  • DAT ligands on Cocaine-Food Choice in Monkeys
  • MDPV high-responders to evaluate candidate medications
Show more Behavioral Pharmacology

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 © 2023 by the American Society for Pharmacology and Experimental Therapeutics