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Anesth Analg 2002;95:573-577
© 2002 International Anesthesia Research Society

ANESTHETIC PHARMACOLOGY

Nonhalogenated Anesthetic Alkanes and Perhalogenated Nonimmobilizing Alkanes Inhibit {alpha}4ß2 Neuronal Nicotinic Acetylcholine Receptors

Douglas E. Raines, MD*{dagger}, Robert J. Claycomb, BS{dagger}, and Stuart A. Forman, MD PhD*{dagger}

Departments of Anesthesia, *Harvard Medical School; and {dagger}Massachusetts General Hospital, Boston, Massachusetts

Address correspondence and reprint requests to Dr. D. E. Raines, Department of Anesthesia, Massachusetts General Hospital, 32 Fruit St., Boston, MA 02114. Address e-mail to draines{at}partners.org

The nonhalogenated anesthetic alkanes, cyclopropane and butane, do not enhance {gamma}-aminobutyric acid-elicited GABAergic currents, suggesting that these agents produce anesthesia via interactions with other molecular targets. Perhalogenated nonimmobilizing alkanes, such as 1,2-dichlorohexafluorocyclobutane and 2,3-dichlorooctafluorobutane, also fail to enhance GABAergic currents, but display specific behavioral effects that are distinct from those of structurally similar anesthetics. At concentrations predicted to be anesthetic, 1,2-dichlorohexafluorocyclobutane and 2,3-dichlorooctafluorobutane produce amnesia but fail to produce immobility. Neuronal nicotinic acetylcholine (nACh) receptors are sensitive to many anesthetics and are thought to have an important role in learning and memory. We postulated that neuronal nACh receptors might mediate the common amnestic action of nonhalogenated and perhalogenated alkanes. To test the hypothesis that neuronal nACh receptors have a role in mediating the behavioral effects of general anesthetics and nonimmobilizers, we quantified the inhibitory potencies of nonhalogenated anesthetic alkanes and perhalogenated nonimmobilizing alkanes on currents mediated by {alpha}4ß2 neuronal nACh receptors. Our studies reveal that anesthetics and nonimmobilizers significantly inhibit {alpha}4ß2 neuronal nACh receptors at concentrations that suppress learning and with potencies that correlate with their hydrophobicities. These results support the hypothesis that {alpha}4ß2 neuronal nACh receptors mediate the amnestic actions of alkanes but not their immobilizing actions.

IMPLICATIONS: The results of this study suggest that the immobilizing actions of general anesthetics do not result from the inhibition of {alpha}4ß2 neuronal nicotinic acetylcholine receptors. However, the inhibition of neuronal nicotinic acetylcholine receptors may account for the amnestic activities of general anesthetics and nonimmobilizers.




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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 © 2002 by the International Anesthesia Research Society.