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 ArticleABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION

Quantification of Pharmacodynamic Interactions between Dexmedetomidine and Midazolam in the Rat

Cornelis J. J. G. Bol, John P. W. Vogelaar, Jian-Ping Tang and Jaap W. Mandema
Journal of Pharmacology and Experimental Therapeutics July 2000, 294 (1) 347-355;
Cornelis J. J. G. Bol
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
John P. W. Vogelaar
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jian-Ping Tang
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jaap W. Mandema
  • 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 pharmacodynamic (PD) interaction between the benzodiazepine agonist midazolam and the α2-adrenergic agonist dexmedetomidine was characterized for defined measures of anesthetic action and cardiovascular and ventilatory side effects in 33 rats. For various combinations of constant plasma concentrations of midazolam (0.1–20 μg/ml) and dexmedetomidine (0.3–19 ng/ml) obtained by target-controlled infusion, the whisker reflex (WR), righting reflex (RR), startle reflex to noise (SR), tail clamp response (TC), and corneal reflex (CR) were assessed. EEG (power in 0.5–3.5-Hz frequency band), mean arterial pressure, and heart rate were recorded continuously. Blood gas values and arterial drug concentrations were determined regularly. The nature and extent of PD interaction was quantified by the model parameter synergy (SYN < 0, antagonism; SYN = 0, additivity; andSYN > 0, synergy). With increasing drug concentrations WR was lost first, followed by RR, SR, TC, and CR. These effects were accompanied by an increase of the EEG measure. The drug interaction was synergistic for all stimulus-response measures and the degree of synergy increased with deeper levels of central nervous system depression (SYN was 7.3, 145, 560, 374, and 1490 for WR, RR, SR, TC, and CR, respectively). The cardiovascular side effects of dexmedetomidine, evaluated at similar PD endpoints, were reduced in the presence of midazolam. Ventilatory side effects were minor for all drug combinations. The nature and extent of the PD interactions were not reflected in the EEG measure.

Footnotes

  • Send reprint requests to: Cornelis J.J.G. Bol, Ph.D., Department of Clinical Pharmacokinetics, Janssen Pharmaceutica, B-2340 Beerse, Belgium. E-mail: kbol{at}janbe.jnj.com

  • ↵1 This study was supported in part by a National Institutes of Health Shannon Award GM-51309. This research was conducted at the Department of Anesthesia, Stanford University School of Medicine, Stanford, CA.

  • ↵2 Current address: Department of Clinical Pharmacokinetics, Janssen Pharmaceutica, Beerse, Belgium.

  • ↵3 Current address: Department of Anesthesiology, Leiden University Medical Center, Leiden, the Netherlands.

  • ↵4 Current address: Department of Nonclinical Drug Safety, Hoffman-La Roche, Nutley, NJ.

  • ↵5 Current address: Pharsight Corporation, Mountain View, CA.

  • Abbreviations:
    CNS
    central nervous system
    PK
    pharmacokinetic
    PD
    pharmacodynamic
    bpm
    beats per minute
    RR
    righting reflex
    MAP
    mean arterial pressure
    TCI
    target-controlled infusion
    WR
    whisker reflex
    SR
    startle reflex to noise
    TC
    tail clamp response
    CR
    corneal reflex
    SYN
    synergy
    N
    steepness of the curves
    GABA
    γ-aminobutyric acid
    • Received November 4, 1999.
    • Accepted March 15, 2000.
  • 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: 294 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 294, Issue 1
1 Jul 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.
Quantification of Pharmacodynamic Interactions between Dexmedetomidine and Midazolam in the Rat
(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 ArticleABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION

Quantification of Pharmacodynamic Interactions between Dexmedetomidine and Midazolam in the Rat

Cornelis J. J. G. Bol, John P. W. Vogelaar, Jian-Ping Tang and Jaap W. Mandema
Journal of Pharmacology and Experimental Therapeutics July 1, 2000, 294 (1) 347-355;

Citation Manager Formats

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

Share
Research ArticleABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION

Quantification of Pharmacodynamic Interactions between Dexmedetomidine and Midazolam in the Rat

Cornelis J. J. G. Bol, John P. W. Vogelaar, Jian-Ping Tang and Jaap W. Mandema
Journal of Pharmacology and Experimental Therapeutics July 1, 2000, 294 (1) 347-355;
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

  • Transport Is Not Rate-Limiting in Morphine Glucuronidation in the Single-Pass Perfused Rat Liver Preparation
  • Enhanced Hepatic Uptake and Bioactivity of Type α1(I) Collagen Gene Promoter-Specific Triplex-Forming Oligonucleotides after Conjugation with Cholesterol
  • Characterization of P-glycoprotein Inhibition by Major Cannabinoids from Marijuana
Show more ABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION

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 © 2023 by the American Society for Pharmacology and Experimental Therapeutics