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 ArticleNEUROPHARMACOLOGY

Probable Involvement of the 5-Hydroxytryptamine4Receptor in Methotrexate-Induced Delayed Emesis in Dogs

Hisashi Yamakuni, Hiroe Sawai, Yasue Maeda, Katsunori Imazumi, Hiroyuki Sakuma, Masahiko Matsuo, Seitaro Mutoh and Jiro Seki
Journal of Pharmacology and Experimental Therapeutics March 2000, 292 (3) 1002-1007;
Hisashi Yamakuni
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hiroe Sawai
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yasue Maeda
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Katsunori Imazumi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hiroyuki Sakuma
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Masahiko Matsuo
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Seitaro Mutoh
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jiro Seki
  • 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

Delayed emesis in cancer patients undergoing chemotherapy remains a significant problem. The pathogenesis of delayed emesis is still obscure. It was recently demonstrated that methotrexate (MTX), an anticancer drug, evoked delayed emesis in dogs in a manner similar to its actions in humans. We evaluated the antiemetic activity of FK1052, a potent antagonist for both the 5-hydroxytryptamine (HT)3and 5-HT4 receptors, on delayed emesis induced by MTX in beagle dogs. Animal behavior was recorded for 3 days using a video camera. Delayed emesis lasting up to 72 h was observed in dogs treated with MTX (2.5 mg/kg i.v.), but acute emesis did not occur. The following antiemetics, at the dose that prevents cisplatin-induced acute emesis in dogs, were administered i.v. as multiple injections every 12 h during days 2 to 3. FK1052 (1 and 3.2 mg/kg) significantly reduced the emetic episodes caused by MTX, whereas ondansetron (1 mg/kg), a selective 5-HT3 receptor antagonist, was not effective. The emetic episodes induced by MTX were also inhibited by another 5-HT3/4 receptor antagonist, tropisetron (1 mg/kg). CP-122,721 (0.1 mg/kg), a potent selective tachykinin NK1 receptor antagonist, significantly reduced the emetic responses to MTX. Copper sulfate-induced emesis in dogs was also prevented by FK1052, tropisetron, and CP-122,721 but not by ondansetron. FK1052, tropisetron, and ondansetron had negligible affinity for the NK1 receptor at 1 μM. These results suggest that the 5-HT4 receptor may be in part involved in the production of delayed emesis induced by MTX in dogs and that FK1052 may be a useful drug against both acute and delayed emesis induced by cancer chemotherapy.

Footnotes

  • Send reprint requests to: Dr. Hisashi Yamakuni, Department of Metabolic Diseases, Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Kashima 2-1-6, Yodogawa-ku, Osaka 532-8514, Japan. E-mail:hisashi_yamakuni{at}po.fujisawa.co.jp

  • Abbreviations:
    5-HT
    5-hydroxytryptamine
    MTX
    methotrexate
    5-MeOT
    5-methoxytryptamine
    CHO
    Chinese hamster ovary
    p-APMSF
    p-amidinophenyl methanesulfonyl fluoride HCl
    CNS
    central nervous system
    • Received September 23, 1999.
    • Accepted November 29, 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: 292 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 292, Issue 3
1 Mar 2000
  • 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.
Probable Involvement of the 5-Hydroxytryptamine4Receptor in Methotrexate-Induced Delayed Emesis in Dogs
(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

Probable Involvement of the 5-Hydroxytryptamine4Receptor in Methotrexate-Induced Delayed Emesis in Dogs

Hisashi Yamakuni, Hiroe Sawai, Yasue Maeda, Katsunori Imazumi, Hiroyuki Sakuma, Masahiko Matsuo, Seitaro Mutoh and Jiro Seki
Journal of Pharmacology and Experimental Therapeutics March 1, 2000, 292 (3) 1002-1007;

Citation Manager Formats

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

Share
Research ArticleNEUROPHARMACOLOGY

Probable Involvement of the 5-Hydroxytryptamine4Receptor in Methotrexate-Induced Delayed Emesis in Dogs

Hisashi Yamakuni, Hiroe Sawai, Yasue Maeda, Katsunori Imazumi, Hiroyuki Sakuma, Masahiko Matsuo, Seitaro Mutoh and Jiro Seki
Journal of Pharmacology and Experimental Therapeutics March 1, 2000, 292 (3) 1002-1007;
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
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • D1 agonist vs. methylphenidate on PFC working memory
  • Iclepertin (BI 425809) in schizophrenia-related models
  • Obesity Thwarts Preconditioning in TBI
Show more Neuropharmacology

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