JOURNAL HOME CME HOME THIS MONTH PAST ISSUES ETOC COLLECTIONS
AUTHORS REVIEWERS EDITORIAL BOARD FEEDBACK RSS HELP
A&A International Anesthesia Research Society
 QUICK SEARCH:   [advanced]


     


This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a colleague
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (5)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ahrens, J.
Right arrow Articles by Bufler, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ahrens, J.
Right arrow Articles by Bufler, J.
Related Collections
Right arrow Mechanisms
Right arrow Pharmacology

Anesth Analg 2004;99:91-96
© 2004 International Anesthesia Research Society
doi: 10.1213/01.ANE.0000120083.10269.54


ANESTHETIC PHARMACOLOGY

2,6 Di-tert-butylphenol, a Nonanesthetic Propofol Analog, Modulates {alpha}1ß Glycine Receptor Function in a Manner Distinct from Propofol

Jörg Ahrens, MD*, Gertrud Haeseler, MD*, Martin Leuwer, MD{dagger}, Bahram Mohammadi, MD{ddagger}, Klaus Krampfl, MD{ddagger}, Reinhard Dengler, MD{ddagger}, and Johannes Bufler, MD{ddagger}

Departments of *Anaesthesiology and {ddagger}Neurology and Neurophysiology, Hannover Medical School, Hannover, Germany; and {dagger}University Department of Anaesthesia, The University of Liverpool, Liverpool, United Kingdom

Gertrud Haeseler, MD, Department of Anaesthesiology, OE 8050, Hannover Medical School, D-30623 Hannover, Germany. Address e-mail to Haeseler.Gertrud{at}MH-Hannover.de

The anesthetic propofol (2,6 diisopropylphenol) mediates some of its effects by activating inhibitory chloride currents in the lower brainstem and spinal cord. The effects comprise direct activation of {gamma}-aminobutyric acid-A and glycine receptors in the absence of the natural agonist, as well as potentiation of the effect of submaximal agonist concentrations. Replacement of propofol’s isopropyl groups by di-tert-butyl groups yields a compound without in vivo anesthetic effects. We have studied the effects of propofol and 2,6 di-tert-butylphenol on chloride inward currents via rat {alpha}1ß glycine receptors heterologously expressed in human embryonic kidney cells. Propofol, but not 2,6 di-tert-butylphenol, directly activated glycine receptors; half-maximal current activation was observed with propofol 114 ± 27 µM. Both compounds potentiated the effect of a submaximal glycine concentration (10 µM) to a maximum value of 136% ± 71% (propofol) and 279% ± 109% (2,6 di-tert-butylphenol) of the response to glycine 10 µM. The 50% effective concentration for this effect was 12.5 ± 6.4 µM and 9.4 ± 10.2 µM for propofol and 2,6 di-tert-butylphenol, respectively. Propofol and its nonanesthetic structural analog do not differ in their ability to coactivate the glycine receptor but differ in their ability to directly activate the receptor in the absence of the natural agonist.

IMPLICATIONS: This in vitro study shows that, at the glycine receptor level, propofol does not differ from its nonanesthetic structural analog 2,6 di-tert-butylphenol in its ability to enhance the effect of small glycine concentrations but differs in its potential to directly activate chloride inward currents in the absence of the natural agonist.




This article has been cited by other articles:


Home page
Anesth. Analg.Home page
M. Barann, I. Linden, S. Witten, and B. W. Urban
Molecular Actions of Propofol on Human 5-HT3A Receptors: Enhancement as Well as Inhibition by Closely Related Phenol Derivatives
Anesth. Analg., March 1, 2008; 106(3): 846 - 857.
[Abstract] [Full Text] [PDF]




Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press
Copyright © 2004 by the International Anesthesia Research Society.