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 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
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (17)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Eger, E. I
Right arrow Articles by Hudlicky, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Eger, E. I, II
Right arrow Articles by Hudlicky, T.
Anesth Analg 1999;88:884
© 1999 International Anesthesia Research Society


GENERAL ARTICLES

Nonimmobilizers and Transitional Compounds May Produce Convulsions by Two Mechanisms

Edmond I Eger, II, MD*, Donald D. Koblin, PhD, MD*,{dagger}, James Sonner, MD*, Diane Gong, BS*, Michael J. Laster, DVM*, Pompiliu Ionescu, MD*, Michael J. Halsey, DPhil{ddagger}, and Tomas Hudlicky, PhD§

*Department of Anesthesia, University of California, San Francisco; {dagger}Veteran’s Administration Hospital, San Francisco, California; {ddagger}Nuffield Department of Anaesthetics, Oxford, United Kingdom; and §Department of Chemistry, University of Florida, Gainesville, Florida

Address correspondence to Dr. Eger, Department of Anesthesia, S-455, University of California, San Francisco, CA 94143-0464. Address e-mail to edmond-eger{at}quickmail.ucsf.edu

Some inhaled compounds cause convulsions. To better appreciate the physical basis for this property, we correlated the partial pressures that produced convulsions in rats with the lipophilicity (nonpolarity) and hydrophilicity (polarity) of 45 compounds: 3 n-alkanes, 18 n-haloalkanes, 3 halogenated aromatic compounds, 3 cycloalkanes and 3 halocycloalkanes, 13 halogenated ethers, and 2 noble gases (He and Ne). In most cases, convulsions were quantified by averaging the alveolar partial pressures just below the pressures that caused and slightly higher pressures that did cause clonic convulsions (ED50). The ED50 did not correlate with hydrophilicity (the saline/gas partition coefficient), nor was there an obvious correlation with molecular structure. For 80% of compounds (36 of 45), the ED50 correlated closely (r2 = 0.99) with lipophilicity (the olive oil/gas partition coefficient). Perhaps because they block the effect of GABA on GABAA receptors, five compounds were more potent than would be predicted from their lipophilicity. Conversely, four compounds may have been less potent than would be predicted because they (like conventional inhaled anesthetics) enhance the effect of GABA on GABAA receptors.

Implications: Nonimmobilizers and transitional compounds may produce convulsions by two mechanisms. One correlates with lipophilicity (nonpolarity), and the other correlates with an action on GABAA receptors.




This article has been cited by other articles:


Home page
Anesth. Analg.Home page
M. M. Sedensky and P. G. Morgan
Genetics and the Evolution of the Anesthetic Response
Anesth. Analg., September 1, 2008; 107(3): 855 - 858.
[Full Text] [PDF]


Home page
Anesth. Analg.Home page
E. D. Zarnowska, R. A. Pearce, A. A. Saad, and M. Perouansky
The {gamma}-Subunit Governs the Susceptibility of Recombinant {gamma}-Aminobutyric Acid Type A Receptors to Block by the Nonimmobilizer 1,2-dichlorohexafluorocyclobutane (F6, 2N)
Anesth. Analg., August 1, 2005; 101(2): 401 - 406.
[Abstract] [Full Text] [PDF]


Home page
Anesth. Analg.Home page
M. Perouansky, M. I. Banks, and R. A. Pearce
The Differential Effects of the Nonimmobilizer 1,2-Dichlorohexafluorocyclobutane (F6, 2N) and Isoflurane on Extrasynaptic Gamma-Aminobutyric AcidA Receptors
Anesth. Analg., June 1, 2005; 100(6): 1667 - 1673.
[Abstract] [Full Text] [PDF]


Home page
Anesth. Analg.Home page
E. I Eger II, Y. Xing, R. Pearce, S. Shafer, M. J. Laster, Y. Zhang, M. S. Fanselow, and J. M. Sonner
Isoflurane Antagonizes the Capacity of Flurothyl or 1,2-Dichlorohexafluorocyclobutane to Impair Fear Conditioning to Context and Tone
Anesth. Analg., April 1, 2003; 96(4): 1010 - 1018.
[Abstract] [Full Text] [PDF]


Home page
Anesth. Analg.Home page
D. E. Raines, R. J. Claycomb, and S. A. Forman
Modulation of GABAA Receptor Function by Nonhalogenated Alkane Anesthetics: The Effects on Agonist Enhancement, Direct Activation, and Inhibition
Anesth. Analg., January 1, 2003; 96(1): 112 - 118.
[Abstract] [Full Text] [PDF]


Home page
Anesth. Analg.Home page
E. I Eger II, D. Gong, Y. Xing, D. E. Raines, and P. Flood
Acetylcholine Receptors and Thresholds for Convulsions from Flurothyl and 1,2-Dichlorohexafluorocyclobutane
Anesth. Analg., December 1, 2002; 95(6): 1611 - 1615.
[Abstract] [Full Text] [PDF]


Home page
Anesth. Analg.Home page
C. M. Borghese and R. A. Harris
Anesthetic-Induced Immobility: Neuronal Nicotinic Acetylcholine Receptors Are No Longer in the Picture
Anesth. Analg., September 1, 2002; 95(3): 509 - 511.
[Full Text] [PDF]


Home page
Anesth. Analg.Home page
D. E. Raines, R. J. Claycomb, and S. A. Forman
Nonhalogenated Anesthetic Alkanes and Perhalogenated Nonimmobilizing Alkanes Inhibit {alpha}4{beta}2 Neuronal Nicotinic Acetylcholine Receptors
Anesth. Analg., September 1, 2002; 95(3): 573 - 577.
[Abstract] [Full Text] [PDF]


Home page
Anesth. Analg.Home page
P. G. Morgan, G. W. Radke, and M. M. Sedensky
Effects of Nonimmobilizers and Halothane on Caenorhabditis elegans
Anesth. Analg., October 1, 2000; 91(4): 1007 - 1012.
[Abstract] [Full Text] [PDF]


Home page
Anesth. Analg.Home page
D. D. Koblin, M. J. Laster, P. Ionescu, D. Gong, E. I Eger II, M. J. Halsey, and T. Hudlicky
Polyhalogenated Methyl Ethyl Ethers: Solubilities and Anesthetic Properties
Anesth. Analg., May 1, 1999; 88(5): 1161 - 1167.
[Abstract] [Full Text] [PDF]




Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins and Stanford University Libraries' HighWire Press®. Copyright 1999 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press
Copyright © 1999 by the International Anesthesia Research Society.