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
Drug Metabolism & Disposition
  • 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
Drug Metabolism & Disposition

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 dmd on Facebook
  • Follow dmd on Twitter
  • Follow ASPET on LinkedIn
Abstract

Studies on the glucuronidation of dopamine D-1 receptor antagonists, SCH 39166 and SCH 23390, by human liver microsomes.

T R Tephly, B Coffman, P Styczynski, G Rios, D M Charkowski, M Vanrollins, R D McQuade and C E Tedford
Drug Metabolism and Disposition September 1994, 22 (5) 713-718;
T R Tephly
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
B Coffman
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
P Styczynski
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
G Rios
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
D M Charkowski
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
M Vanrollins
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
R D McQuade
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
C E Tedford
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

Dopamine D-1 receptor antagonists are currently under investigation for use as antipsychotic agents. Two potent and selective D-1 receptor antagonists, SCH 39166 and SCH 23390, have been studied extensively in various experimental animal models. SCH 39166 has a more prolonged duration of action in primates in vivo and a lower rate of in vitro glucuronidation by microsomes from squirrel monkey liver. Because the rate of glucuronidation seems to govern the duration of action and may limit the use of these agents in humans, the glucuronidation of SCH 39166 and SCH 23390 by microsomes isolated from human liver was studied. The rates of glucuronide formation (Vmax) for SCH 39166 were much lower than those of SCH 23390, yet the KM values were similar. Therefore, the average efficiency (Vmax/KM) of SCH 39166 glucuronidation was only 14% that of SCH 23390. These results agree with previous studies in hepatic microsomes from squirrel monkeys. Marked inhibition of SCH 39166 glucuronidation by SCH 23390 and its pharmacologically inactive stereoisomer, SCH 23388, was observed. The inactive stereoisomer of SCH 39166, SCH 39165, was a weak inhibitor. In contrast, substrates for morphine UDP-glucuronosyltransferase (UGT), and p-nitrophenol, an alternative substrate for numerous human hepatic UGTs, did not inhibit SCH 39166 glucuronidation. Further separation of human hepatic UGTs activities using chromatofocusing chromatography indicated that SCH 39166 UGT activity was distinct from human hepatic UGT2B15 and human hepatic pI 6.2 UGT activity. Thus, a unique human hepatic UGT may be involved in SCH 39166 glucuronidation.(ABSTRACT TRUNCATED AT 250 WORDS)

 

DMD 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

Drug Metabolism and Disposition
Vol. 22, Issue 5
1 Sep 1994
  • Table of Contents
  • Table of Contents (PDF)
  • Index by author
  • Back Matter (PDF)
  • 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 Drug Metabolism & Disposition 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 on the glucuronidation of dopamine D-1 receptor antagonists, SCH 39166 and SCH 23390, by human liver microsomes.
(Your Name) has forwarded a page to you from Drug Metabolism & Disposition
(Your Name) thought you would be interested in this article in Drug Metabolism & Disposition.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Abstract

Studies on the glucuronidation of dopamine D-1 receptor antagonists, SCH 39166 and SCH 23390, by human liver microsomes.

T R Tephly, B Coffman, P Styczynski, G Rios, D M Charkowski, M Vanrollins, R D McQuade and C E Tedford
Drug Metabolism and Disposition September 1, 1994, 22 (5) 713-718;

Citation Manager Formats

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

Share
Abstract

Studies on the glucuronidation of dopamine D-1 receptor antagonists, SCH 39166 and SCH 23390, by human liver microsomes.

T R Tephly, B Coffman, P Styczynski, G Rios, D M Charkowski, M Vanrollins, R D McQuade and C E Tedford
Drug Metabolism and Disposition September 1, 1994, 22 (5) 713-718;
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

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 DMD
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Journal of Pharmacology and Experimental Therapeutics
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-009X (Online)

Copyright © 2023 by the American Society for Pharmacology and Experimental Therapeutics