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

Differential Actions of Antiparkinson Agents at Multiple Classes of Monoaminergic Receptor. I. A Multivariate Analysis of the Binding Profiles of 14 Drugs at 21 Native and Cloned Human Receptor Subtypes

Mark J. Millan, Lisa Maiofiss, Didier Cussac, Valérie Audinot, Jean-A. Boutin and Adrian Newman-Tancredi
Journal of Pharmacology and Experimental Therapeutics November 2002, 303 (2) 791-804; DOI: https://doi.org/10.1124/jpet.102.039867
Mark J. Millan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lisa Maiofiss
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Didier Cussac
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Valérie Audinot
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jean-A. Boutin
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Adrian Newman-Tancredi
  • 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

Because little comparative information is available concerning receptor profiles of antiparkinson drugs, affinities of 14 agents were determined at diverse receptors implicated in the etiology and/or treatment of Parkinson's disease: human (h)D1, hD2S, hD2L, hD3, hD4, and hD5 receptors; human 5-hydroxytryptamine (5-HT)1A, h5-HT1B, h5-HT1D, h5-HT2A, h5-HT2B, and h5-HT2Creceptors; hα1A-, hα1B-, hα1D-, hα2A-, hα2B-, hα2C-, rat α2D-, hβ1-, and hβ2-adrenoceptors (ARs); and native histamine1 receptors. A correlation matrix (294 pKi values) demonstrated substantial “covariance”. Correspondingly, principal components analysis revealed that axis 1, which accounted for 76% variance, was associated with the majority of receptor types: drugs displaying overall high versus modest affinities migrated at opposite extremities. Axis 2 (7% of variance) differentiated drugs with high affinity for hD4 and H1 receptors versus hα1-AR subtypes. Five percent of variance was attributable to axis 3, which distinguished drugs with marked affinity for hβ1- and hβ2-ARs versus hD5and 5-HT2A receptors. Hierarchical (cluster) analysis of global homology generated a dendrogram differentiating two major groups possessing low versus high affinity, respectively, for multiple serotonergic and hD5 receptors. Within the first group, quinpirole, quinerolane, ropinirole, and pramipexole interacted principally with hD2, hD3, and hD4receptors, whereas piribedil and talipexole recognized dopaminergic receptors and hα2-ARs. Within the second group, lisuride and terguride manifested high affinities for all sites, with roxindole/bromocriptine, cabergoline/pergolide, and 6,7-dihydroxy-N,N-dimethyl-2-ammotetralin (TL99)/apomorphine comprising three additional subclusters of closely related ligands. In conclusion, an innovative multivariate analysis revealed marked heterogeneity in binding profiles of antiparkinson agents. Actions at sites other than hD2 receptors likely participate in their (contrasting) functional profiles.

Footnotes

  • ↵1 Rat α2D-ARs are the rodent homolog of human hα2A-ARs, to which they show marked differences as concerns affinities of certain drug classes (Hieble et al., 1995).

  • ↵2 A more detailed discussion of the actions of drugs at hD2S, hD2L, hD3, and hD4 receptors, multiple classes of α1- and α2-AR and multiple subtypes of 5-HT receptor is to be found in the accompanying articles, which document drug efficacies at these sites.

  • DOI: 10.1124/jpet.102.039867

  • Abbreviations:
    DA
    dopamine
    l-DOPA
    l-dihydroxyphenylacetic acid
    h
    human
    AR
    adrenoceptor
    5-HT
    5-hydroxytryptamine
    TL99
    6,7-dihydroxy-N,N-dimethyl-2-ammotetralin
    H
    histamine
    M1
    muscarinic
    PCA
    principle component analysis
    PC
    principle component
    • Received June 12, 2002.
    • Accepted July 22, 2002.
  • 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: 303 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 303, Issue 2
1 Nov 2002
  • Table of Contents
  • 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.
Differential Actions of Antiparkinson Agents at Multiple Classes of Monoaminergic Receptor. I. A Multivariate Analysis of the Binding Profiles of 14 Drugs at 21 Native and Cloned Human Receptor Subtypes
(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

Differential Actions of Antiparkinson Agents at Multiple Classes of Monoaminergic Receptor. I. A Multivariate Analysis of the Binding Profiles of 14 Drugs at 21 Native and Cloned Human Receptor Subtypes

Mark J. Millan, Lisa Maiofiss, Didier Cussac, Valérie Audinot, Jean-A. Boutin and Adrian Newman-Tancredi
Journal of Pharmacology and Experimental Therapeutics November 1, 2002, 303 (2) 791-804; DOI: https://doi.org/10.1124/jpet.102.039867

Citation Manager Formats

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

Differential Actions of Antiparkinson Agents at Multiple Classes of Monoaminergic Receptor. I. A Multivariate Analysis of the Binding Profiles of 14 Drugs at 21 Native and Cloned Human Receptor Subtypes

Mark J. Millan, Lisa Maiofiss, Didier Cussac, Valérie Audinot, Jean-A. Boutin and Adrian Newman-Tancredi
Journal of Pharmacology and Experimental Therapeutics November 1, 2002, 303 (2) 791-804; DOI: https://doi.org/10.1124/jpet.102.039867
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
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • P-Glycoprotein Apical Efflux Ratio for Compound Optimization
  • Pharmacology of Carbamate Insecticides at Melatonin Receptors
  • Metalloporphyrins modify disease outcomes in parkinsonism
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