This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (10) Citing Articles via Google Scholar Google Scholar Articles by Raines, D. E. Articles by Forman, S. A. Search for Related Content PubMed PubMed Citation Articles by Raines, D. E. Articles by Forman, S. A. Related Collections Mechanisms Pharmacology

---

ANESTHETIC PHARMACOLOGY

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

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

Departments of Anesthesia, *Harvard Medical School; and 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 -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 ₄ß₂ neuronal nACh receptors. Our studies reveal that anesthetics and nonimmobilizers significantly inhibit ₄ß₂ neuronal nACh receptors at concentrations that suppress learning and with potencies that correlate with their hydrophobicities. These results support the hypothesis that 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 _4ß2 neuronal nicotinic acetylcholine receptors. However, the inhibition of neuronal nicotinic acetylcholine receptors may account for the amnestic activities of general anesthetics and nonimmobilizers.

This article has been cited by other articles:

				E. I. Eger II, D. E. Raines, S. L. Shafer, H. C. Hemmings Jr, and J. M. Sonner Is a New Paradigm Needed to Explain How Inhaled Anesthetics Produce Immobility? Anesth. Analg., September 1, 2008; 107(3): 832 - 848. [Abstract] [Full Text] [PDF]

				D. E. Raines, F. Gioia, R. J. Claycomb, and R. J. Stevens The N-Methyl-D-aspartate Receptor Inhibitory Potencies of Aromatic Inhaled Drugs of Abuse: Evidence for Modulation by Cation-{pi} Interactions J. Pharmacol. Exp. Ther., October 1, 2004; 311(1): 14 - 21. [Abstract] [Full Text] [PDF]

				J. M. Sonner, J. F. Antognini, R. C. Dutton, P. Flood, A. T. Gray, R. A. Harris, G. E. Homanics, J. Kendig, B. Orser, D. E. Raines, et al. Inhaled Anesthetics and Immobility: Mechanisms, Mysteries, and Minimum Alveolar Anesthetic Concentration Anesth. Analg., September 1, 2003; 97(3): 718 - 740. [Abstract] [Full Text] [PDF]

				J. A. Campagna, K. W. Miller, and S. A. Forman Mechanisms of Actions of Inhaled Anesthetics N. Engl. J. Med., May 22, 2003; 348(21): 2110 - 2124. [Full Text] [PDF]

				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]

				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]