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 ArticleGASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

N-[2-[4-(2-Methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-nitrophenyl) Cyclohexanecarboxamide: A Novel Pre- and Postsynaptic 5-Hydroxytryptamine1A Receptor Antagonist Active on the Lower Urinary Tract

A. Leonardi, L. Guarneri, E. Poggesi, P. Angelico, C. Velasco, A. Cilia and R. Testa
Journal of Pharmacology and Experimental Therapeutics December 2001, 299 (3) 1027-1037;
A. Leonardi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
L. Guarneri
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
E. Poggesi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
P. Angelico
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
C. Velasco
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
A. Cilia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
R. Testa
  • 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

N-[2-[4-(2-Methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-nitrophenyl) cyclohexanecarboxamide (Rec 15/3079) was synthesized with the aim of obtaining a novel compound with 5-hydroxytryptamine (5-HT)1A antagonistic properties and activity in controlling bladder function at the level of the central nervous system. Rec 15/3079 showed a selective high affinity for the 5-HT1A receptor (Ki = 0.2 nM). At the human recombinant 5-HT1A receptor, Rec 15/3079 acted as a competitive, neutral antagonist in that it did not modify basal [35S]guanosine-5′-O-(3-thio)triphosphate binding to HeLa cell membranes but shifted the activation isotherm to 5-HT to the right, in a parallel manner, with a pKb value of 10.5. Accordingly, Rec 15/3079 (i.v.) potently antagonized 8-hydroxy-2-dipropylaminotetralin (8-OH-DPAT)-induced hypothermia in mice (ID50 = 20 μg/kg) and 8-OH-DPAT-induced forepaw treading in rats (ID50 = 36 μg/kg). In vitro Rec 15/3079 was poorly active in antagonizing carbachol-induced bladder (pD′2 = 5.03) and norepinephrine-induced urethral (apparent pKb = 6) contractions. However, in anesthetized rats, Rec 15/3079 (10–100 μg/kg i.v.) blocked isovolumic bladder contractions with no effect on their amplitude. In conscious rats and guinea pigs with bladders filled with saline, Rec 15/3079 (300–1000 μg/kg i.v.) increased bladder volume capacity (BVC) without affecting bladder contractility. In conscious rats with bladders filled with dilute acetic acid, Rec 15/3079 (300 μg/kg i.v.) reversed the decrease of BVC induced by the acid. To evaluate apparent selective effect on lower urinary tract reflexes, Rec 15/3079 was tested in experimental models for sedative, analgesic, anxiolytic, and antidepressant activity. Rec 15/3079 showed only a slight decrease in the duration of immobility in the behavioral despair test (antidepressant activity) at 1 mg/kg i.v. No anxiolytic activity was observed at 10 mg/kg i.v. No effect was observed in the hot plate test, but Rec 15/3079 increased tail-flick latencies after 3 to 10 mg/kg i.v. In conclusion, these studies demonstrate that Rec 15/3079 is endowed with favorable effects on bladder function, and it is devoid of unwanted side effects at the level of central nervous system at doses at least 10-fold higher than those active on the bladder.

Footnotes

  • Abbreviations:
    5-HT
    5-hydroxytryptamine
    GTPγS
    guanosine-5′-O-(3-thio)triphosphate
    8-OH-DPAT
    8-hydroxy-2-dipropylaminotetralin
    BVC
    bladder volume capacity
    bw
    body weight
    MP
    micturition pressure
    Rec 15/3079
    N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-nitrophenyl) cyclohexanecarboxamide
    WAY 100635
    N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridyl)cyclohexanecarboxamide
    DT
    disappearance time
    • Received July 12, 2001.
    • Accepted September 7, 2001.
  • 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: 299 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 299, Issue 3
1 Dec 2001
  • 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.
N-[2-[4-(2-Methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-nitrophenyl) Cyclohexanecarboxamide: A Novel Pre- and Postsynaptic 5-Hydroxytryptamine1A Receptor Antagonist Active on the Lower Urinary Tract
(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 ArticleGASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

N-[2-[4-(2-Methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-nitrophenyl) Cyclohexanecarboxamide: A Novel Pre- and Postsynaptic 5-Hydroxytryptamine1A Receptor Antagonist Active on the Lower Urinary Tract

A. Leonardi, L. Guarneri, E. Poggesi, P. Angelico, C. Velasco, A. Cilia and R. Testa
Journal of Pharmacology and Experimental Therapeutics December 1, 2001, 299 (3) 1027-1037;

Citation Manager Formats

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

Share
Research ArticleGASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

N-[2-[4-(2-Methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-nitrophenyl) Cyclohexanecarboxamide: A Novel Pre- and Postsynaptic 5-Hydroxytryptamine1A Receptor Antagonist Active on the Lower Urinary Tract

A. Leonardi, L. Guarneri, E. Poggesi, P. Angelico, C. Velasco, A. Cilia and R. Testa
Journal of Pharmacology and Experimental Therapeutics December 1, 2001, 299 (3) 1027-1037;
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

  • DR7dA alleviated PF in vivo and in vitro
  • Ligustrazine Attenuates Liver Fibrosis
  • MK-5046, BRS-3 allosteric agonist
Show more Gastrointestinal, Hepatic, Pulmonary, and Renal

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