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
OtherENDOCRINE PHARMACOLOGY

Unique Preclinical Characteristics of GG745, A Potent Dual Inhibitor of 5AR

H. Neal Bramson, David Hermann, Kenneth W. Batchelor, Frank W. Lee, Michael K. James and Stephen V. Frye
Journal of Pharmacology and Experimental Therapeutics September 1997, 282 (3) 1496-1502;
H. Neal Bramson
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David Hermann
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kenneth W. Batchelor
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Frank W. Lee
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael K. James
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Stephen V. Frye
  • 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

Selective inhibition of type 2 5α-reductase has been shown to be efficacious in the treatment of benign prostatic hyperplasia. Pharmacokinetic and pharmacodynamic results are reported of treatment with a potent inhibitor of both 5α-reductase isozymes, GG745, in rats, dogs and men. In the rat, GG745 has a similar effect on DHT-driven prostatic growth as finasteride, another dual 5α-reductase inhibitor in this species. However, GG745 appears to be more potent in the rat, a result that likely reflects the greater inherent potency and terminal half-life of GG745 (14 hr) compared with that of finasteride (1 hr). These pharmacokinetic differences are also maintained in the dog (65 and 4 hr for GG745 and finasteride, respectively). From these results, the literature, and in vitro studies, we estimated doses of GG745 likely to prove efficacious in reducing DHT levels in man. These estimated values were predictive of single-dose effects of GG745 in man. Results from single-dose evaluations in man indicate that GG745 has a terminal half-life of ∼240 hr, and single doses of >10 mg decreased DHT levels significantly more than did single 5-mg doses of finasteride. These data support the hypothesis that a molecule (GG745) that effectively inhibits both 5α-reductases will lower serum DHT levels significantly more than a molecule that inhibits only a single 5α-reductase isozyme (e.g., finasteride, a selective inhibitor of the type 2 enzyme in man).

Footnotes

  • Send reprint requests to: H. Neal Bramson, Glaxo Wellcome Research Institute, 5 Moore Drive, Research Triangle Park, NC 27709.

  • ↵1 Patent WO95/07927, March 23, 1995.

  • ↵2 Receptor Assay Descriptions, 1994.

  • ↵3 D. Stuart, unpublished observations.

  • Abbreviations:
    BPH
    benign prostatic hyperplasia
    i.v.
    intravenous
    5AR
    3-oxo-steroid-Δ4-reductase
    r5AR1
    rat 5α-reductase 1
    r5AR2
    rat 5α-reductase 2
    GC
    gas chromatography
    ms
    mass spectometry
    GG745
    17β-N-(2,5-bis(trifluoromethyl))phenyl-carbamoyl-4-aza-5α-androst-1-en-3-one
    finasteride
    17β-[N-(1,1-dimethylethyl)carbamoyl]-4-aza-5α-androst-1-en-3-one
    4-mA
    17-β-N,N-diethylcarbamoyl-4-methyl-4-aza-5α-androstan-3-one
    T
    testosterone
    DHT
    dihydrotesterone
    HPLC
    high-performance liquid chromatography
    NADPH
    nicotinamide adenine dinucleotide phosphate
    • Received October 7, 1996.
    • Accepted May 12, 1997.
  • 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
Vol. 282, Issue 3
1 Sep 1997
  • 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.
Unique Preclinical Characteristics of GG745, A Potent Dual Inhibitor of 5AR
(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
OtherENDOCRINE PHARMACOLOGY

Unique Preclinical Characteristics of GG745, A Potent Dual Inhibitor of 5AR

H. Neal Bramson, David Hermann, Kenneth W. Batchelor, Frank W. Lee, Michael K. James and Stephen V. Frye
Journal of Pharmacology and Experimental Therapeutics September 1, 1997, 282 (3) 1496-1502;

Citation Manager Formats

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

Unique Preclinical Characteristics of GG745, A Potent Dual Inhibitor of 5AR

H. Neal Bramson, David Hermann, Kenneth W. Batchelor, Frank W. Lee, Michael K. James and Stephen V. Frye
Journal of Pharmacology and Experimental Therapeutics September 1, 1997, 282 (3) 1496-1502;
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
    • Experimental Procedures
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Efficacy of an Insulin-Like Growth Factor-Interleukin-3 Fusion Protein in Reversing the Hematopoietic Toxicity Associated with Azidothymidine in Mice
  • The Effect of Orally Administered Clodronate on Bone Mineral Density and Bone Geometry in Ovariectomized Rats
  • Inhibition of Bufalin on Pituitary and Testicular Function in Rats
Show more ENDOCRINE PHARMACOLOGY

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