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 ArticleArticle

Mechanisms of Action of OPC-28326, a Selective Hindlimb Vasodilator

Kensuke Orito, Takashi Imaizumi, Kenji Yoshida, Hiroyuki Fujiki, Masami Kishi, Shuji Teramoto, Michinori Tanaka, Hiroshi Shimizu, Michiaki Tominaga, Yukio Kimura, Junichi Kambayashi and Toyoki Mori
Journal of Pharmacology and Experimental Therapeutics November 1999, 291 (2) 604-611;
Kensuke Orito
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Takashi Imaizumi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kenji Yoshida
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hiroyuki Fujiki
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Masami Kishi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Shuji Teramoto
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michinori Tanaka
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hiroshi Shimizu
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michiaki Tominaga
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yukio Kimura
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Junichi Kambayashi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Toyoki Mori
  • 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 unique cardiovascular profile of OPC-28326 [4-(N-methyl-2-phenylethylamino)-1-(3,5-dimethyl-4-propionylaminobenzoyl)piperidine hydrochloride monohydrate] provides insight into basic mechanisms of this new drug as determined by experiments in dogs and rats. In anesthetized open-chest dogs, an i.v. administration of a low dose (0.3 and 1.0 μg/kg) of OPC-28326 selectively increased femoral artery blood flow with only minimal action on systemic blood pressure, heart rate and coronary, carotid, vertebral, renal, and mesenteric blood flows. Biochemical study suggests that OPC-28326 had no effect on phosphodiesterase-3 and -5. OPC-28326 dose-dependently inhibited phenylephrine-induced increases in blood pressure in spinally anesthetized dogs. The potency of OPC-28326 was, however, about 180 times lower than that of prazosin. Although binding studies have revealed an affinity of OPC-28326 to serotonin 5-HT2receptors, the drug is without effect, except at very high concentrations, on serotonin-induced contraction in an isolated canine femoral artery preparation. The potency of OPC-28326 on the increase in femoral artery blood flow was about 14 times higher than that of prazosin but was at about the same level as that obtained with yohimbine in canine autoperfused femoral artery preparations. In perfused rat hindlimb preparations, OPC-28326 inhibited the decrease in perfusion flow induced by brimonidine, a selective α2-adrenoceptor agonist. The potency of OPC-28326 was at least 10 times less than that of yohimbine. Taken together, the results show that at low doses, OPC-28326 selectively exerts a potent vasodilating effect on the femoral arterial bed, in part due to an α2-adrenoceptor-blocking activity.

Footnotes

  • Send reprint requests to: Kensuke Orito, D.V.M., Ph.D., Thrombosis & Vascular Research Laboratory, Otsuka Pharmaceutical Co., Ltd., 463-10 Kagasuno Kawauchi-cho Tokushima 771-0192, Japan. E-mail: k_orito{at}research.otsuka.co.jp

  • ↵1 Current address: Thrombosis & Vascular Research Laboratory, Otsuka Pharmaceutical Co., Ltd., 463-10 Kagasuno Kawauchi-cho Tokushima 771-0192, Japan.

  • ↵2 Current address: Maryland Research Laboratories, Otsuka America Pharmaceutical Inc., 9900 Medical Center Dr. Rockville, MD 20850.

  • Abbreviations:
    FBF
    femoral artery blood flow
    BP
    blood pressure
    SR
    sinoatrial rate
    ASA
    anterior septal artery
    OPC-28326
    4-(N-methyl-2-phenylethylamino)-1-(3,5-dimethyl-4-propionylaminobenzoyl)piperidine hydrochloride monohydrate
    CF
    contractile force
    POAD
    peripheral occlusive arterial disease
    CBF
    coronary artery blood flow
    HR
    heart rate
    VBF
    vertebral artery blood flow
    CaBF
    carotid artery blood flow
    RBF
    renal artery blood flow
    MBF
    mesenteric artery blood flow
    5-HT
    5-hydroxytryptamine (serotonin)
    • Received April 16, 1999.
    • Accepted July 16, 1999.
  • 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: 291 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 291, Issue 2
1 Nov 1999
  • 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.
Mechanisms of Action of OPC-28326, a Selective Hindlimb Vasodilator
(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 ArticleArticle

Mechanisms of Action of OPC-28326, a Selective Hindlimb Vasodilator

Kensuke Orito, Takashi Imaizumi, Kenji Yoshida, Hiroyuki Fujiki, Masami Kishi, Shuji Teramoto, Michinori Tanaka, Hiroshi Shimizu, Michiaki Tominaga, Yukio Kimura, Junichi Kambayashi and Toyoki Mori
Journal of Pharmacology and Experimental Therapeutics November 1, 1999, 291 (2) 604-611;

Citation Manager Formats

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

Share
Research ArticleArticle

Mechanisms of Action of OPC-28326, a Selective Hindlimb Vasodilator

Kensuke Orito, Takashi Imaizumi, Kenji Yoshida, Hiroyuki Fujiki, Masami Kishi, Shuji Teramoto, Michinori Tanaka, Hiroshi Shimizu, Michiaki Tominaga, Yukio Kimura, Junichi Kambayashi and Toyoki Mori
Journal of Pharmacology and Experimental Therapeutics November 1, 1999, 291 (2) 604-611;
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

  • CRV431 Decreases Liver Fibrosis and Tumor Development
  • Prolonged Inhibition ofO 6-Methylguanine DNA Methyltransferase in Human Tumor Cells by O 6-Benzylguanine In Vitro and In Vivo
  • Reduction of 5-Hydroxytryptamine (5-HT)1A-Mediated Temperature and Neuroendocrine Responses and 5-HT1A Binding Sites in 5-HT Transporter Knockout Mice
Show more Article

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 © 2022 by the American Society for Pharmacology and Experimental Therapeutics