Is a new paradigm needed to explain how inhaled anesthetics produce immobility?

Anesthesia and Analgesia

Volumn 107, Issue 3, 2008, Pages 832-848

  Eger, Edmond I ^a,e   Raines, Douglas E ^b   Shafer, Steven L ^c   Hemmings Jr , Hugh C ^d   Sonner, James M ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b MASSACHUSETTS GENERAL HOSPITAL   (United States)

^c Columbia University ^*  (United States)

^d WEILL CORNELL MEDICAL COLLEGE   (United States)

^e UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 AMINOBUTYRIC ACID; 4 AMINOBUTYRIC ACID A RECEPTOR; CALCIUM CHANNEL; GLUTAMATE RECEPTOR; OPIATE; POTASSIUM CHANNEL; SEROTONIN 3 RECEPTOR; VOLTAGE GATED CALCIUM CHANNEL; VOLTAGE GATED POTASSIUM CHANNEL; INHALATION ANESTHETIC AGENT; LIGAND; SODIUM CHANNEL;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; DRUG MECHANISM; DRUG TARGETING; IMMOBILIZATION; NOCICEPTIVE STIMULATION; NONHUMAN; PRIORITY JOURNAL; RAT; ANALGESIA; ANIMAL; BIOLOGICAL MODEL; ELECTRICITY; HUMAN; METABOLISM; MOUSE; REVIEW; THEORETICAL MODEL;

ANALGESIA; ANESTHETICS, INHALATION; ANIMALS; ELECTROSTATICS; HUMANS; IMMOBILIZATION; LIGANDS; MICE; MODELS, BIOLOGICAL; MODELS, GENETIC; MODELS, THEORETICAL; RECEPTORS, GABA-A; RECEPTORS, GLUTAMATE; RECEPTORS, SEROTONIN, 5-HT3; SODIUM CHANNELS;

EID: 51449090737     PISSN: 00032999     EISSN: None     Source Type: Journal    
DOI: 10.1213/ane.0b013e318182aedb     Document Type: Review

References (231)

1. Merkel G, Eger EI II. A comparative study of halothane and halopropane anesthesia. Including a method for determining equipotency. Anesthesiology 1963;24:346-57
2. Saidman LJ, Eger EI II. Effect of nitrous oxide and of narcotic premedication on the alveolar concentration of halothane required for anesthesia. Anesthesiology 1964;25:302-6
3. Antognini JF, Raines DE, Solt K, Barter LS, Atherley RJ, Bravo E, Laster MJ, Jankowska K, Eger EI II. Hexafluorobenzene acts in the spinal cord, whereas o-difluorobenzene acts in both brain and spinal cord, to produce immobility. Anesth Analg 2007;104:822-8
4. Antognini JF, Schwartz K. Exaggerated anesthetic requirements in the preferentially anesthetized brain. Anesthesiology 1993;79:1244-9
5. Rampil IJ. Anesthetic potency is not altered after hypothermic spinal cord transection in rats. Anesthesiology 1994;80:606-10
6. Roizen MF, Horrigan RW, Frazer BF. Anesthetic doses blocking adrenergic (stress) and cardiovascular responses to incision- MAC BAR. Anesthesiology 1981;54:390-8
7. France CJ, Plumer HM, Eger EI II, Wahrenbrock EA. Ventilatory effects of isoflurane (Forane) or halothane when combined with morphine, nitrous oxide and surgery. Br J Anaesth 1974;46:117-20
8. Katoh T, Kobayashi S, Suzuki A, Iwamoto T, Bito H, Ikeda K. The effect of fentanyl on sevoflurane requirements for somatic and sympathetic responses to surgical incision. Anesthesiology 1999;90:398-405
9. Rehberg B, Ruschner R, Fisher M, Ebeling BJ, Hoeft A. [Concentration-dependent changes in the latency and amplitude of somatosensory-evoked potentials by desflurane, isoflurane and sevoflurane]. Anaesthesiol Intensivmed Notfallmed Schmerzther 1998;33:425-9
10. Antognini JF, Carstens E. Increasing isoflurane from 0.9 to 1.1 minimum alveolar concentration minimally affects dorsal horn cell responses to noxious stimulation. Anesthesiology 1999;90:208-14
11. Barter LS, Mark LO, Jinks SL, Carstens EE, Antognini JF. Immobilizing doses of halothane, isoflurane or propofol, do not preferentially depress noxious heat-evoked responses of rat lumbar dorsal horn neurons with ascending projections. Anesth Analg 2008;106:985-90
12. Merrill AW, Barter LS, Rudolph U, Eger EI II, Antognini JF, Carstens MI, Carstens E. Propofol's effects on nociceptive behavior and spinal c-fos expression after intraplantar formalin injection in mice with a mutation in the gammaaminobutyric acid-type(A) receptor beta3 subunit. Anesth Analg 2006;103:478-83
13. Reinacher PC, Priebe HJ, Blumrich W, Zentner J, Scheufler KM. The effects of stimulation pattern and sevoflurane concentration on intraoperative motor-evoked potentials. Anesth Analg 2006;102:888-95
14. Jinks SL, Atherley RJ, Dominguez CL, Sigvardt KA, Antognini JF. Isoflurane disrupts central pattern generator activity and coordination in the lamprey isolated spinal cord. Anesthesiology 2005;103:567-75
15. Antognini JF, Atherley RJ, Dutton RC, Laster MJ, Eger EI II, Carstens E. The excitatory and inhibitory effects of nitrous oxide on spinal neuronal responses to noxious stimulation. Anesth Analg 2007;104:829-35
16. Eger EI II, Tang M, Liao M, Laster MJ, Solt K, Flood P, Jenkins A, Raines D, Hendrickx J, Shafer S, Yasumasa T, Sonner JM. Inhaled anesthetics do not combine to produce synergistic effects regarding MAC. Anesth Analg 2008:479-85
17. Hendrickx JFA, Eger EI, II, Sonner JM, Shafer SL. Is synergy the rule? A review of anesthetic drug interactions producing hypnosis and immobility. Anesth Analg 2008:494-506
18. Shafer SL, Hendrickx JFA, Flood P, Sonner J, Eger EI II. Additivity versus synergy: a theoretical analysis of implications for anethetic mechanisms. Anesth Analg 2008:507-24
19. Franks NP, Lieb WR. Temperature dependence of the potency of volatile general anesthetics. Anesthesiology 1996;84:716-20
20. Krasowski MD, Harrison NL. General anaesthetic actions on ligand-gated ion channels. Cell Mol Life Sci 1999;55:1278-303
21. Squires RF, Saederup E. Additivities of compounds that increase the numbers of high affinity [3H]muscimol binding sites by different amounts define more than 9 GABA(A) receptor complexes in rat forebrain: implications for schizophrenia and clozapine research. Neurochem Res 2000;25:1587-601
22. Davies M, Thuynsma RP, Dunn SM. Effects of propofol and pentobarbital on ligand binding to GABAA receptors suggest a similar mechanism of action. Can J Physiol Pharmacol 1998;76:46-52
23. Sebel LE, Richardson JE, Singh SP, Bell SV, Jenkins A. Additive effects of sevoflurane and propofol on gamma-aminobutyric acid receptor function. Anesthesiology 2006;104:1176-83
24. Bertaccini EJ, Trudell JR, Franks NP. The common chemical motifs within anesthetic binding sites. Anesth Analg 2007;104: 318-24
25. Sewell JC, Sear JW. Determinants of volatile general anesthetic potency: a preliminary three-dimensional pharmacophore for halogenated anesthetics. Anesth Analg 2006;102:764-71
26. Sewell JC, Sear JW. Derivation of preliminary threedimensional pharmacophores for nonhalogenated volatile anesthetics. Anesth Analg 2004;99:744-51
27. Lysko GS, Robinson JL, Casto R, Ferrone RA. The stereospecific effects of isoflurane isomers in vivo. Eur J Pharmacol 1994;263:25-9
28. Won A, Oh I, Laster MJ, Popovich J, Eger EI II, Sonner JM. Chirality in anesthesia I: minimum alveolar concentration of secondary alcohol enantiomers. Anesth Analg 2006;103:81-4
29. Brosnan R, Gong D, Cotten J, Keshavaprasad B, Yost CS, Eger EI II, Sonner JM. Chirality in anesthesia II: stereoselective modulation of ion channel function by secondary alcohol enantiomers. Anesth Analg 2006;103:86-91
30. White PF, Schuttler J, Shafer A, Stanski DR, Horai Y, Trevor AJ. Comparative pharmacology of the ketamine isomers. Studies in volunteers. Br J Anaesth 1985;57:197-203
31. Dickinson R, Peterson BK, Banks P, Simillis C, Martin JC, Valenzuela CA, Maze M, Franks NP. Competitive inhibition at the glycine site of the .-methyl-d-aspartate receptor by the anesthetics xenon and isoflurane: evidence from molecular modeling and electrophysiology. Anesthesiology 2007;107: 756-67
32. Meyer HH. Theorie der Alkoholnarkose. Arch Exptl Pathol Pharmakol 1899;42:109-18
33. Overton E. Studien ü ber die Narkose, Zugleich ein Beitrag zur allgemeinen Pharmakologie. Gustav Fischer: Jena; 1901:1-195
34. Franks NP, Lieb WR. Do general anaesthetics act by competitive binding to specific receptors? Nature 1984;310:599-601
35. Koblin DD, Chortkoff BS, Laster MJ, Eger EI II, Halsey MJ, Ionescu P. Polyhalogenated and perfluorinated compounds that disobey the Meyer-Overton hypothesis. Anesth Analg 1994;79:1043-8
36. Chipot C, Wilson MA, Pohorille A. Interactions of anesthetics with the hexane-water interface. J Phys Chem B 1996;101: 782-91
37. Pohorille A, Wilson MA, Cieplak P. Interaction of alcohols and anesthetics with the water-hexane interface: a molecular dynamics study. Prog Colloid Polym Sci 1997;103:29-40
38. Abraham MH, Acree WE Jr, Mintz C, Payne S. Effect of anesthetic structure on inhalation anesthesia: implications for the mechanism. J Pharm Sci 2008;97:2373-84
39. Janoff AS, Pringle MJ, Miller KW. Correlation of general anesthetic potency with solubility in membranes. Biochem Biophys Acta 1981;649:125-8
40. Pringle MJ, Brown KB, Miller KM. Can the lipid theories of anesthesia account for the cutoff in anesthetic potency in homologous series of alcohols. Mol Pharmacol 1981;19:49-55
41. Sonner JM. A hypothesis on the origin and evolution of the response to inhaled anesthetics. Anesth Analg 2008;107:849-54
42. Eckenhoff R. Why can all of biology be anesthetized? Anesth Analg 2008;107:859-61
43. Lynch C. Meyer and Overton revisited. Anesth Analg 2008;107:864-7
44. Sedensky MM, Morgan PG. Genetics and the evolution of the anesthetic response. Anesth Analg 2008;107:855-8
45. Crowder CM. Does natural selection explain the universal response of metazoans to volatile anesthetics? Anesth Analg 2008;107:862-3
46. Durieux ME. The evolution of anesthetic sensitivity and the evolution of a paper. Anesth Analg 2008;107:737-8
47. Nandini-Kishore SG, Mattox SM, Martin CE, Thompson GA Jr. Membrane changes during growth of Tetrahymena in the presence of ethanol. Biochim Biophys Acta 1979;551:315-27
48. Nandini-Kishore SG, Kitajima Y, Thompson GA Jr. Membrane fluidizing effects of the general anesthetic methoxyflurane elicit an acclimation response in Tetrahymena. Biochim Biophys Acta 1977;471:157-61
49. Koblin DD, Wang HH. Chronic exposure to inhaled anesthetics increases cholesterol content in Acholeplasma laidlawi. Biochim Biophys Acta 1981;649:717-25
50. Ingram LO. Adaptation of membrane lipids to alcohols. J Bacteriol 1976;125:670-8
51. Yang L, Sonner JM. Anesthetic-like modulation of receptor function by surfactants: a test of the interfacial theory of anesthesia. Anesth Analg 2008;107:868-74
52. Brosnan RJ, Yang L, Milutinovic PS, Zhao J, Laster MJ, Eger EI II, Sonner JM. Ammonia has anesthetic properties. Anesth Analg 2007;104:1430-3
53. Yang L, Zhao J, Milutinovic PS, Brosnan RJ, Eger EI II, Sonner JM. Anesthetic properties of the ketone bodies betahydroxybutyric acid and acetone. Anesth Analg 2007;105: 673-9
54. Cantor RS. Receptor desensitization by neurotransmitters in membranes: are neurotransmitters the endogenous anesthetics? Biochemistry 2003;42:11891-7
55. Milutinovic PS, Yang L, Cantor RS, Eger EI II, Sonner JM. Anesthetic-like modulation of a gamma-aminobutyric acid type A, strychnine-sensitive glycine, and .-methyl-d-aspartate receptors by coreleased neurotransmitters. Anesth Analg 2007;105:386-92
56. Antognini JF, Carstens E, Atherley R. Does the immobilizing effect of thiopental in brain exceed that of halothane? Anesthesiology 2002;96:980-6
57. Rampil IJ, Mason P, Singh H. Anesthetic potency (MAC) is independent of forebrain structures in the rat. Anesthesiology 1993;78:707-12
58. Garcia-Fernandez J, Parodi E, Garcia P, Matute E, I AG-d-S, Cediel R, Gilsanz F. Clinical actions of subarachnoid sevoflurane administration in vivo: a study in dogs. Br J Anaesth 2005;95:530-4
59. Chai YF, Yang J, Liu J, Song HB, Yang JW, Liu SL, Zhang WS, Wang QW. Epidural anaesthetic effect of the 8% emulsified isoflurane: a study in rabbits. Br J Anaesth 2008;100:109-15
60. Maingret F, Lauritzen I, Patel AJ, Heurteaux C, Reyes R, Lesage F, Lazdunski M, Honore E. TREK-1 is a heat-activated background K(-) channel. EMBO J 2000;19:2483-91
61. Eger EI II, Johnson BH. MAC of I-653 in rats, including a test of the effect of body temperature and anesthetic duration. Anesth Analg 1987;66:974-6
62. Violet JM, Downie DL, Nakisa RC, Lieb WR, Franks NP. Differential sensitivities of mammalian neuronal and muscle nicotinic acetylcholine receptors to general anesthetics. Anesthesiology 1997;86:866-74
63. Zhang Y, Laster MJ, Eger EI II, Sharma M, Sonner JM. Blockade of acetylcholine receptors does not change the dose of etomidate required to produce immobility in rats. Anesth Analg 2007;104:850-2
64. Jurd R, Arras M, Lambert S, Drexler B, Siegwart R, Crestani F, Zaugg M, Vogt KE, Ledermann B, Antkowiak B, Rudolph U. General anesthetic actions in vivo strongly attenuated by a point mutation in the GABA(A) receptor beta3 subunit. FASEB J 2003;17:250-2
65. Liao M, Sonner JM, Jurd R, Rudolph U, Borghese CM, Harris RA, Laster MJ, Eger EI II. Beta3-containing gamma-aminobutyric acidA receptors are not major targets for the amnesic and immobilizing actions of isoflurane. Anesth Analg 2005;101:412-18
66. Katayama S, Irifune M, Kikuchi N, Takarada T, Shimizu Y, Endo C, Takata T, Dohi T, Sato T, Kawahara M. Increased gamma-aminobutyric acid levels in mouse brain induce loss of righting reflex, but not immobility, in response to noxious stimulation. Anesth Analg 2007;104:1422-9
67. Deady J, Koblin DD, Eger EI II, Heavner JE, D'Aoust B. Anesthetic potencies and the unitary theory of narcosis. Anesth Analg 1981;60:380-4
68. Sonner JM, Antognini JF, Dutton RC, Flood P, Gray AT, Harris RA, Homanics GE, Kendig JJ, Orser BA, Raines DE, Trudell JR, Vissel B, Eger EI II. Inhaled anesthetics and immobility: mechanisms, mysteries, and MAC. Anesth Analg 2003;97:718-40
69. Franks NP, Lieb WR. Molecular and cellular mechanisms of general anaesthesia. Nature 1994;367:607-14
70. Harris RA, Mihic SJ, Dildy-Mayfield JE, Machu TK. Actions of anesthetics on ligand-gated ion channels: role of receptor subunit composition. FASEB J 1995;9:1454-62
71. Hemmings HC Jr, Akabas MH, Goldstein PA, Trudell JR, Orser BA, Harrison NL. Emerging molecular mechanisms of general anesthetic action. Trends Pharmacol Sci 2005;26:503-10
72. Krasowski MD, Harrison NL. The actions of ether, alcohol and alkane general anaesthetics on GABAA and glycine receptors and the effects of TM2 and TM3 mutations. Br J Pharmacol 2000;129:731-43
73. Mihic SJ, Ye Q, Wick MJ, Koltchine VV, Krasowski MD, Finn SE, Mascia MP, Valenzuela CF, Hanson KK, Greenblatt EP, Harris RA, Harrison NL. Sites of alcohol and volatile anaesthetic action on GABAA and glycine receptors. Nature 1997;389:385-9
74. Flood P, Sonner JM, Gong D, Coates KM. Heteromeric nicotinic inhibition by isoflurane does not mediate MAC or loss of righting reflex. Anesthesiology 2002;97:902-5
75. Eger EI II, Zhang Y, Laster MJ, Flood P, Kendig JJ, Sonner JM. Acetylcholine receptors do not mediate the immobilization produced by inhaled anesthetics. Anesth Analg 2002;94:1500-4
76. Wang MY, Rampil IJ, Kendig JJ. Ethanol directly depresses AMPA and NMDA glutamate currents in spinal cord motor neurons independent of actions on GABAA or glycine receptors. J Pharmacol Exp Ther 1999;290:362-7
77. Do SH, Kamatachi GL, Durieux ME. The effects of isoflurane on native and chimeric muscarinic acetylcholine receptors: the role of protein kinase C. Anesth Analg 2001;93:375-81
78. Minami K, Minami M, Harris RA. Inhibition of 5-hydroxytryptamine type 2A receptor-induced currents by n-alcohols and anesthetics. J Pharmacol Exp Ther 1997;281:1136-43
79. Minami K, Gereau RW, Minami M, Heinemann SF, Harris RA. Effects of ethanol and anesthetics on type 1 and 5 metabotropic glutamate receptors expressed in Xenopus laevi. oocytes. Mol Pharmacol 1998;53:148-56
80. Raines DE, Claycomb RJ, Forman SA. Nonhalogenated anesthetic alkanes and perhalogenated nonimmobilizing alkanes inhibit -4-2 neuronal nicotinic acetylcholine receptors. Anesth Analg 2002;95:573-7
81. Pidoplichko VI, Dani JA: Acid-sensitive ionic channels in midbrain dopamine neurons are sensitive to ammonium, which may contribute to hyperammonemia damage. Proc Natl Acad Sci USA 2006;103:11376-80
82. Wu LJ, Duan B, Mei YD, Gao J, Chen JG, Zhuo M, Xu L, Wu M, Xu TL. Characterization of acid-sensing ion channels in dorsal horn neurons of rat spinal cord. J Biol Chem 2004;279:43716-24
83. Baron A, Voilley N, Lazdunski M, Lingueglia E. Acid sensing ion channels in dorsal spinal cord neurons. J Neurosci 2008;28:1498-508
84. Duan B, Wu LJ, Yu YQ, Ding Y, Jing L, Xu L, Chen J, Xu TL. Upregulation of acid-sensing ion channel ASIC1a in spinal dorsal horn neurons contributes to inflammatory pain hypersensitivity. J Neurosci 2007;27:11139-48
85. Eisele JH, Eger EI II, Muallem M. Narcotic properties of carbon dioxide in the dog. Anesthesiology 1967;28:856-65
86. Seitz PA, ter Reit, M, Rush W, Merrell W. Adenosine decreases the minimum alveolar concentration of halothane in dogs. Anesthesiology 1990;73:990-4
87. Ma HC, Wang YF, Feng CS, Zhao H, Dohi S. Effects of adenosine agonist R-phenylisopropyl-adenosine on halothane anesthesia and antinociception in rats. Acta Pharmacol Sin 2005;26:181-5
88. Nicholls EA, Louie GL, Prokocimer PG, Maze M. Halothane anesthetic requirements are not affected by aminophylline treatment in rats and dogs. Anesthesiology 1986;65:637-41
89. Govinda R, Kasuya Y, Orhan-Sungur M, Turan A, Sessler DI. Aminophylline does not increase the minimum alveolar concentration of desflurane. Anesthesiolgy 2007;107:A1919 (Abstract)
90. Suzuki A, Katoh T, Ikeda K. The effect of adenosine triphosphate on sevoflurane requirements for minimum alveolar anesthetic concentration and minimum alveolar anesthetic concentration-awake. Anesth Analg 1998;86:179-83
91. Hara K, Yamakura T, Sata T, Harris RA. The effects of anesthetics and ethanol on alpha2 adrenoceptor subtypes expressed with G protein-coupled inwardly rectifying potassium channels in Xenopus oocytes. Anesth Analg 2005;101:1381-8
92. Rabin BC, Reid K, Guo TZ, Gustafsson E, Zhang C, Maze M. Sympatholytic and minimum anesthetic concentration-sparing responses are preserved in rats rendered tolerant to the hypnotic and analgesic action of dexmedetomidine, a selective --2 adrenergic agonist. Anesthesiology 1996;85:565-73
93. Bloor BC, Flacke WE. Reduction in halothane anesthetic requirement by clonidine, and alpha-adrenergic agonist. Anesth Analg 1982;61:741-5
94. Eger EI II, Xing Y, Laster MJ, Sonner JM. --2 adrenoreceptors probably do not mediate the immobility produced by inhaled anesthetics. Anesth Analg 2003;96:1661-4
95. Study RE. Isoflurane inhibits multiple voltage-gated calcium currents in hippocampal pyramidal neurons. Anesthesiology 1994;81:104-16
96. Lingamaneni R, Hemmings HC Jr. Differential interaction of anaesthetics and antiepileptic drugs with neuronal Na- channels, Ca2- channels, and GABA(A) receptors. Br J Anaesth 2003;90:199-211
97. Hall AC, Lieb WR, Franks NP. Insensitivity of P-type calcium channels to inhalational and intravenous general anesthetics. Anesthesiology 1994;81:117-23
98. Graham MD, Hopkins PM, Harrison SM. Antagonistic actions of halothane and sevoflurane on spontaneous Ca2- release in rat ventricular myocytes. Anesthesiology 2006;105:58-64
99. Petrenko AB, Tsujita M, Kohno T, Sakimura K, Baba H. Mutation of alpha1G T-type calcium channels in mice does not change anesthetic requirements for loss of the righting reflex and minimum alveolar concentration but delays the onset of anesthetic induction. Anesthesiology 2007;106:1177-85
100. Tanifuji Y, Zhang Y, Liao M, Eger EI II, Laster MJ, Sonner JM. Do dopamine receptors mediate part of MAC? Anesth Analg 2006;103:1177-81
101. Miller RD, Way WL, Eger EI II. The effects of alphamethyldopa, reserpine, guanethidine, and iproniazid on minimum alveloar anesthetic requirement (MAC). Anesthesiology 1968;29:1153-8
102. Johnston R, White P, Eger EI II. Comparative effects of dextroamphetamine and reserpine on halothane and cyclopropane anesthetic requirements. Anesth Analg 1975;54:655-9
103. Raja SN, Moscicki JC, Woodside JR Jr, DiFazio CA. The effect of acute phencyclidine administration on cyclopropane requirement (MAC) in rats. Anesthesiology 1982;56:275-9
104. Segal IS, Vickery RG, Walton JK, Doze VA, Maze M. Dexmedetomidine diminishes halothane anesthetic requirements in rats through a postsynaptic --2 adrenergic receptor. Anesthesiology 1988;69:818-23
105. Mueller RA, Smith RD, Spruill WA, Breese GR. Central monaminergic neuronal effects on minimum alveolar concentrations (MAC) of halothane and cyclopropane in rats. Anesthesiology 1975;42:143-52
106. Krasowski M, Jenkins A, Flood P, Kung A, Hopfinger A, Harrison N. General anesthetic potencies of a series of propofol analogs correlate with potency for potentiation of gammaaminobutyric acid (GABA) current at the GABA(A) receptor but not with lipid solubility. J Pharmacol Exp Ther 2001;297: 338-51
107. Harrison NL, Kugler JL, Jones MV, Greenblatt EP, Pritchett DB. Positive modulation of human --aminobutyric acid type A and glycine receptors by the inhalation anesthetic isoflurane. Mol Pharmacol 1993;44:628-32
108. Grasshoff C, Drexler B, Hentschke H, Thiermann H, Antkowiak B. Cholinergic modulation of sevoflurane potency in cortical and spinal networks in vitro. Anesthesiology 2007;106: 1147-55
109. Sonner JM, Zhang Y, Stabernack C, Abaigar W, Xing Y, Sharma M, Eger EI II. GABA(A) receptor blockade antagonizes the immobilizing action of propofol but not ketamine or isoflurane in a dose-related manner. Anesth Analg 2003;96:706-12
110. Hara K, Eger EI II, Laster MJ, Harris RA. Nonhalogenated alkanes cyclopropane and butane affect neurotransmittergated ion channel and G-protein-coupled receptors: differential actions on GABA(A) and glycine receptors. Anesthesiology 2002;97:1512-20
111. Raines DE, Claycomb RJ, Scheller M, Forman A. Nonhalogenated alkane anesthetics fail to potentiate agonist actions on two ligand-gated channels. Anesthesiology 2001;95:470-7
112. Zhang Y, Sonner JM, Eger EI II, Stabernack CR, Laster MJ, Raines DE, Harris RA. GABAA receptors do not mediate the immobility produced by inhaled anesthetics. Anesth Analg 2004;99:85-90
113. Sonner JM, Cascio M, Xing Y, Fanselow MS, Kralic JE, Morrow AL, Korpi ER, Hardy S, Sloat B, Eger EI II, Homanics GE. Alpha 1 subunit-containing GABA type A receptors in forebrain contribute to the effect of inhaled anesthetics on conditioned fear. Mol Pharmacol 2005;68:61-8
114. Quinlan JJ, Homanics GE, Firestone LL. Anesthesia sensitivity in mice that lack the -3 subunit of the --aminobutyric acid type A receptor. Anesthesiology 1998;88:775-80
115. Eger EI II, Ionescu P, Laster MJ, Fang Z, Gong D, Hudlicky T, Kendig J, Harris A, Trudell J, Pohorille A. MAC of fluorinated alkanols in rats: relevance to theories of narcosis. Anesth Analg 1999;88:867-76
116. Ueno S, Trudell JR, Eger EI II, Harris RA. Actions of fluorinated alkanols on GABAA receptors: relevance to theories of narcosis. Anesth Analg 1999;88:877-83
117. Jones MV, Brooks PA, Harrison NL. Enhancement of gammaaminobutyric acid-activated Cl-currents in cultured rat hippocampal neurones by three volatile anaesthetics. J Physiol (Lond) 1992;449:279-93
118. Wentlandt K, Samoilova M, Carlen PL, El Beheiry H. General anesthetics inhibit gap junction communication in cultured organotypic hippocampal slices. Anesth Analg 2006;102: 1692-8
119. Johnston MF, Simon SA, Ramon F. Interaction of anaesthetics with electrical synapses. Nature 1980;286:498-500
120. Mascia MP, Machu TK, Harris RA. Enhancement of homomeric glycine receptor function by long-chain alcohols and anaesthetics. Br J Pharmacol 1996;119:1331-6
121. Zimmerman SA, Jones MV, Harrison NL. Potentiation of --aminobutyric acid A receptor Cl-current correlates with in vivo anesthetic potency. J Pharmacol Exp Ther 1994;270:987-91
122. Zhang Y, Wu S, Eger EI II, Sonner JM. Neither GABA(A) nor strychnine-sensitive glycine receptors are the sole mediators of MAC for isoflurane. Anesth Analg 2001;92:123-7
123. Zhang Y, Laster MJ, Hara K, Harris RA, Eger EI II, Stabernack CR, Sonner JM. Glycine receptors may mediate part of the immobility produced by inhaled anesthetics. Anesth Analg 2003;96:97-101
124. Kingsmore S, Giros B, Suh D, Bieniarz M, Caron MG, Seldin MF. Glycine receptor beta-subunit gene mutation in spastic mouse associated with LINE-1 element insertion. Nat Genet 1994;7:136-41
125. Quinlan JJ, Ferguson C, Jester K, Firestone LL, Homanics GE. Mice with glycine receptor subunit mutations are both sensitive and resistant to volatile anesthetics. Anesth Analg 2002;95:578-82
126. Ryan SG, Buckwalter MS, Lynch JW, Handford CA, Segura L, Shiang R, Wasmuth JJ, Camper SA, Schofield P, O'Connell P. A missense mutation in the gene encoding the alpha 1 subunit of the inhibitory glycine receptor in the spasmodic mouse. Nat Genet 1994;7:131-5
127. McFarlane C, Warner DS, Todd MM, Nordholm L. AMPA receptor competitive antagonism reduces halothane MAC in rats. Anesthesiology 1992;77:1165-70
128. Dutton RC, Zhang Y, Stabernack CR, Laster MJ, Sonner JM, Eger EI II. Temporal summation governs part of the minimum alvolar concentration (MAC) of isoflurane anesthesia. Anesthesiology 2003;98:1372-7
129. Stabernack C, Sonner JM, Laster M, Zhang Y, Xing Y, Sharma M, Eger EI II. Spinal NMDA receptors may contribute to the immobilizing action of isoflurane. Anesth Analg 2003;96:102-7
130. McFarlane C, Warner DS, Dexter F. Interactions between NMDA and AMPA glutamate receptor antagonists during halothane anesthesia in the rat. Neuropharmacology 1995;34: 659-63
131. Cheng G, Kendig JJ. Enflurane directly depresses glutamate AMPA and NMDA currents in mouse spinal cord motor neurons independent of actions on GABAA or glycine receptors. Anesthesiology 2000;93:1075-84
132. Perouansky M, Kirson ED, Yaari Y. Mechanism of action of volatile anesthetics: effects of halothane on glutamate receptors in vitro. Toxicol Lett 1998;100 -101:65-9
133. Yamakura T, Harris RA. Effects of gaseous anesthetics nitrous oxide and xenon on ligand-gated ion channels: comparison with isoflurane and ethanol. Anesthesiology 2000;93:1095-101
134. Carla V, Moroni F. General anaesthetics inhibit the responses induced by glutamate receptor agonists in the mouse cortex. Neurosci Lett 1992;146:21-4
135. Joo DT, Gong D, Sonner JM, Jia Z, MacDonald JF, Eger EI II, Orser BA. Blockade of AMPA receptors and volatile anesthetics: reduced anesthetic requirements in GluR2 null mutant mice for loss of the righting reflex and antinociception but not minimum alveolar concentration. Anesthesiology 2001;94: 478-88
136. Nishikawa K, MacIver MB. Excitatory synaptic transmission mediated by NMDA receptors is more sensitive to isoflurane than are non-NMDA receptor-mediated responses. Anesthesiology 2000;92:228-36
137. Bar-Peled O, O'Brien RJ, Morrison JH, Rothstein JD. Cultured motor neurons possess calcium-permeable AMPA/kainate receptors. Neuroreport 1999;10:855-9
138. Van Damme P, Van Den Bosch L, Van Houtte E, Callewaert G, Robberecht W. GluR2-dependent properties of AMPA receptors determine the selective vulnerability of motor neurons to excitotoxicity. J Neurophysiology 2002;88:1279-87
139. Petralia RS, Wang YX, Mayat E, Wenthold RJ. Glutamate receptor subunit 2-selective antibody shows a differential distribution of calcium-impermeable AMPA receptors among populations of neurons. J Comp Neurol 1997;385:456-76
140. Ishizaki K, Sasaki M, Karasawa S, Obata H, Nara T, Goto F. Intrathecal co-administration of NMDA antagonist and NK-1 antagonist reduces MAC of isoflurane in rats. Acta Anaesthesiol Scand 1999;43:753-9
141. Dingledine R, Borges K, Bowie D, Traynelis SF. The glutamate receptor ion channels. Pharmacol Rev 1999;51:7-61
142. Minami K, Wick MJ, Stern-Bach Y, Dildy-Mayfield JE, Brozowski SJ, Gonzales EL, Trudell JR, Harris RA. Sites of volatile anesthetic action on kainate (Glutamate receptor 6) receptors. J Biol Chem 1998;273:8248-55
143. Sonner JM, Vissel B, Royle G, Maurer A, Gong D, Baron NV, Harrison N, Fanselow M, Eger EI II. The effect of three inhaled anesthetics in mice harboring mutations in the GluR6 (kainate) receptor gene. Anesth Analg 2005;101:143-8
144. Ishizaki K, Yoon DM, Yoshida N, Tamazaki M, Arai K, Fujita T. Intrathecal administration of .-methyl-d-aspartate receptor antagonist reduces the minimum alveolar anaesthetic concentration of isoflurane in rats. Br J Anaesth 1995;75:636-8
145. Kuroda Y, Strebel S, Rafferty C, Bullock R. Neuroprotective doses of .-methyl-d-aspartate receptor antagonists profoundly reduce the minimum alveolar anesthetic concentration (MAC) for isoflurane in rats. Anesth Analg 1993;77:795-800
146. Flood P, Krasowski MD. Intravenous anesthetics differentially modulate ligand-gated ion channels. Anesthesiology 2000;92: 1418-25
147. Sato Y, Kobayashi E, Murayama T, Mishina M, Seo N. Effect of .-methyl-d-aspartate receptor epsilon1 subunit gene disruption of the action of general anesthetic drugs in mice. Anesthesiology 2005;102:557-61
148. Sato Y, Seo N, Kobayashi E. Ethanol-induced hypnotic tolerance is absent in .-methyl-d-aspartate receptor epsilon 1 subunit knockout mice. Anesth Analg 2006;103:117-20
149. Niemann S, Kanki H, Fukui Y, Takao K, Fukaya M, Hynynen MN, Churchill MJ, Shefner JM, Bronson RT, Brown RH Jr, Watanabe M, Miyakawa T, Itohara S, Hayashi Y. Genetic ablation of NMDA receptor subunit NR3B in mouse reveals motoneuronal and nonmotoneuronal phenotypes. Eur J Neurosci 2007;26:1407-20
150. Liu HT, Hollmann MW, Liu WH, Hoenemann CW, Durieux ME. Modulation of NMDA receptor function by ketamine and magnesium: Part I. Anesth Analg 2001;92:1173-81
151. Yamakura T, Askalany AR, Petrenko AB, Kohno T, Baba H, Sakimura K. The NR3B subunit does not alter the anesthetic sensitivities of recombinant .-methyl-d-aspartate receptors. Anesth Analg 2005;100:1687-92
152. de Sousa LM, Dickinson R, Lieb WR, Franks NP. Contrasting synaptic actions of the inhalational general anesthetics isoflurane and xenon. Anesthesiology 2000;92:1055-66
153. Rex S, Schaefer W, Meyer PH, Rossaint R, Boy C, Setani K, Bull U, Baumert JH. Positron emission tomography study of regional cerebral metabolism during general anesthesia with xenon in humans. Anesthesiology 2006;105:936-43
154. Langsjo JW, Salmi E, Kaisti KK, Aalto S, Hinkka S, Aantaa R, Oikonen V, Viljanen T, Kurki T, Silvanto M, Scheinin H. Effects of subanesthetic ketamine on regional cerebral glucose metabolism in humans. Anesthesiology 2004;100:1065-1071
155. Kaisti KK, Langsjo JW, Aalto S, Oikonen V, Sipila H, Teras M, Hinkka S, Metsahonkala L, Scheinin H. Effects of sevoflurane, propofol, and adjunct nitrous oxide on regional cerebral blood flow, oxygen consumption, and blood volume in humans. Anesthesiology 2003;99:603-13
156. Dutton RC, Laster MJ, Xing Y, Sonner JM, Raines DE, Solt K, Eger EI II. Do .-methyl-d-aspartate receptors mediate the capacity of inhaled anesthetics to suppress the temporal summation that contributes to minimum alveolar concentration? Anesth Analg 2006;102:1412-18
157. Dickenson AH, Sullivan AF. Electrophysiologic studies on the effects of intrathecal morphine on nociceptive neurons in the rat dorsal horn. Pain 1986;24:211-22
158. Eger EI, II, Liao M, Laster MJ, Won A, Popovich J, Raines DE, Solt K, Dutton RC, Cobos FV, Sonner JM. Contrasting roles of the .-methyl-d- aspartate receptor in the production of immobilization by conventional and aromatic anesthetics. Anesth Analg 2006;102:1397-406
159. Solt K, Eger EI II, Raines DE. Differential modulation of human .-methyl-d-aspartate receptors by structurally diverse general anesthetics. Anesth Analg 2006;102:1407-11
160. Englelhardt T, Lowe PR, Galley HF, Webster NR. Inhibition of neuronal nitric oxide synthase reduces isoflurane MAC and motor activity even in nNOS knockout mice. Br J Anaesth 2006;96:361-6
161. Johns RA, Moscicki JC, DiFazio CA. Nitric oxide synthase inhibitor dose-dependently and reversibly reduces the threshold for halothane anesthesia. A role for nitric oxide in mediating consciousness? Anesthesiology 1992;77:779-84
162. Pajewski TN, DiFazio CA, Moscicki JC, Johns RA. Nitric oxide synthase inhibitors, 7-nitro indazole and nitroG-l-arginine methyl ester, dose dependently reduce the threshold for isoflurane anesthesia. Anesthesiology 1996;85:1111-19
163. Ichinose F, Huang PL, Zapol WM. Effects of targeted neuronal nitric oxide synthase gene disruption and nitroG-l-arginine methylester on the threshold for isoflurane anesthesia. Anesthesiology 1995;83:101-8
164. Ichinose F, Mi WD, Miyazaki M, Onouchi T, Goto T, Morita S. Lack of correlation between the reduction of sevoflurane MAC and the cerebellar cyclic GMP concentrations in mice treated with 7-nitroindazole. Anesthesiology 1998;89:143-8
165. Kobayashi S, Katoh T, Iwamoto T, Bito H, Sato S. Effect of the neuronal nitric oxide synthase inhibitor 7-nitroindazole on the righting reflex ED50 and minimum alveolar concentration during sevoflurane anaesthesia in rats. Eur J Anaesthesiol 2003;20:212-19
166. Adachi T, Kurata J, Nakao S, Murakawa M, Shichino T, Shirakami G, Shinomura T, Mori K. Nitric oxide synthase inhibitor does not reduce minimum alveolar anesthetic concentration of halothane in rats. Anesth Analg 1994;78:1154-7
167. Adachi T, Shinomura T, Nakao S, Kurata J, Murakawa M, Shichino T, Seo N, Mori K. Chronic treatment with nitric oxide synthase (NOS) inhibitor profoundly reduces cerebellar NOS activity and cyclic guanosine monophosphate but does not modify minimum alveolar anesthetic concentration. Anesth Analg 1995;81:862-5
168. Way WL, Hosobuchi Y, Johnson BH, Eger EI II. Anesthesia does not increase
169. Katoh T, Ikeda K. The effects of fentanyl on sevoflurane requirements for loss of consciousness and skin incision. Anesthesiology 1998;88:18-24
170. Harper MH, Winter PM, Johnson BH, Eger EI II. Naloxone does not antagonize general anesthesia in the rat. Anesthesiology 1978;49:3-5
171. Pace NL, Wong KC. Failure of naloxone and naltrexone to antagonize halothane anesthesia in the dog. Anesth Analg 1979;58:36-9
172. Levine LL, Winter PM, Nemoto EM, Uram M, Lin MR. Naloxone does not antagonize the analgesic effects of inhalation anesthetics. Anesth Analg 1986;65:330-2
173. de Wolff MH, Leather HA, Wouters PF. Effects of tramadol on minimum alveolar concentration (MAC) of isoflurane in rats. Br J Anaesth 1999;83:780-3
174. Mantz J, Azerad J, Limoge A, Desmonts JM. Transcranial electrical stimulation with Limoge's currents decreases halothane requirements in rats. Evidence for the involvement of endogenous opioids. Anesthesiology 1992;76:253-60
175. Tay AA, Tseng CK, Pace NL, Wong KC, Hong-Goka BC. Failure of narcotic antagonist to alter electroacupuncture modification of halothane anaesthesia in the dog. Can Anaesth Soc J 1982;29:231-5
176. Maze M, Vickery R, Merlone S, Gaba D. Anesthetic and hemodynamic effects of the alpha2-adrenergic agonist, azepexole, in isoflurane-anesthetized dogs. Anesthesiology 1988;68:689-94
177. Michelsen LG, Salmenpera M, Hug CC Jr, Szlam F, Vander- Meer D. Anesthetic potency of remifentanil in dogs. Anesthesiology 1996;84:865-72
178. Dahan A, Sarton E, Teppema L, Olievier C, Nieuwenhuijs D, Matthes HW, Kieffer BL. Anesthetic potency and influence of morphine and sevoflurane on respiration in mu-opioid receptor knockout mice. Anesthesiology 2001;94:824-32
179. Liao M, Laster MJ, Eger EI II, Tang M, Sonner JM. Naloxone does not increase the minimum alveolar anesthetic concentration of sevoflurane in mice. Anesth Analg 2006;102:1452-5
180. Heurteaux C, Guy N, Laigle C, Blondeau N, Duprat F, Mazzuca M, Lang-Lazdunski L, Widmann C, Zanzouri M, Romey G, Lazdunski M. TREK-1, a K(-) channel involved in neuroprotection and general anesthesia. EMBO J 2004;23:2684-95
181. Patel AJ, Honore E, Lesage F, Fink M, Romey G, Lazdunski M. Inhalational anesthetics activate two-pore-domain background K- channels. Nat Neurosci 1999;2:422-6
182. Eger EI II, Saidman LJ, Brandstater B. Temperature dependence of halothane and cyclopropane anesthesia in dogs: correlation with some theories of anesthetic action. Anesthesiology 1965;26:764-70
183. Antognini JG. Hypothermia eliminates isoflurane requirements at 20 degrees C. Anesthesiology 1993;78:1152-6
184. Liu M, Hu X, Liu J. The effect of hypothermia on isoflurane MAC in children. Anesthesiology 2001;94:429-32
185. Linden AM, Sandu C, Aller MI, Vekovischeva OY, Rosenberg PH, Wisden W, Korpi ER. TASK-3 knockout mice exhibit exaggerated nocturnal activity, impairments in cognitive functions, and reduced sensitivity to inhalation anesthetics. J Pharmacol Exp Ther 2007;323:924-34
186. Leonoudakis D, Gray AT, Winegar BD, Kindler CH, Harada M, Taylor DM, Chavez RA, Forsayeth JR, Yost CS. An open rectifier potassium channel with two pore domains in tandem cloned from rat cerebellum. J Neurosci 1998;18:868-77
187. Brosnan RJ, Eger EI II, Laster MJ, Sonner JM. Anesthetic properties of carbon dioxide in the rat. Anesth Analg 2007;105:103-6
188. Gerstin KM, Gong DH, Abdallah M, Winegar BD, Eger EI II, Gray AT. Mutation of KCNK5 or Kir3.2 potassium channels in mice does not change MAC. Anesth Analg 2003;96:1345-1349
189. Zucker JR. ATP-sensitive potassium channel agonists do not alter MAC for isoflurane in rats. Anesthesiology 1992;76:560-3
190. Cotten JF, Keshavaprasad B, Laster MJ, Eger EI II, Yost CS. The ventilatory stimulant doxapram inhibits TASK tandem pore (K2P) potassium channel function but does not affect minimum alveolar anesthetic concentration. Anesth Analg 2006;102: 779-85
191. Xing Y, Zhang Y, Stabernack CR, Eger EI II, Gray AT. The use of the potassium channel activator riluzole to test whether potassium channels mediate the capacity of isoflurane to produce immobility. Anesth Analg 2003;97:1020-4
192. Urbani A, Belluzzi O. Riluzole inhibits the persistent sodium current in mammalian CNS neurons. Eur J Neurosci 2000;12:3567-74
193. Kuo JJ, Lee RH, Zhang L, Heckman CJ. Essential role of the persistent sodium current in spike initiation during slowly rising inputs. J Physiol 2006;574(Pt 3):819-34
194. Tanifuji Y, Eger EI II. Brain sodium, potassium, and osmolality: effects on anesthetic requirement. Anesth Analg 1978;57: 404-10
195. Shnayderman D, Laster MJ, Eger EI II, Oh I, Zhang Y, Jinks SL, Antognini JF, Raines DE. Increases in spinal cerebrospinal fluid potassium concentration do not increase isoflurane MAC in rats. Anesth Analg 2008;107:879-84
196. Vonvoigtlander P, Lewis RA, Neff GL. Kappa opioid analgesia is dependent on serotonergic mechanisms. J Pharmacol Exp Ther 1984;231:270-4
197. Kellstein DE, Malseed RT, Goldstein FJ. Opioid-monamine interactions in spinal antinociception: evidence for serotonin but not norepinephrine reciprocity. Pain 1988;34:85-92
198. Paul D, Mana MJ, Pfaus JG, Pinel JP. Attenuation of morphine analgesia by the S2 antagonists, pirenperone and ketanserin. Pharmacol Biochem Behav 1988;31:641-7
199. Kiefel JM, Paul D, Bodnar RJ. Reduction in opioid and nonopioid forms of swim analgesia by 5-HT2 receptor antagonists. Brain Res 1989;500:231-40
200. Giordano J. Analgesic profile of centrally administered 2-methylserotonin against acute pain in rats. Eur J Pharmacol 1991;199:233-6
201. Coimbra NC, Brandao ML. Effects of 5-HT2 receptors blockade on fear-induced analgesia elicited by electrical stimulation of the deep layers of the superior colliculus and dorsal periaqueductal gray. Behav Brain Res 1997;87:97-103
202. Yamazake N, Umeno H, Kuraishi Y. Involvement of brain serotonergic terminals in the antinociceptive action of peripherally applied calcitonin. Jpn J Pharmacol 1999;81:367-74
203. Bardin L, Lavarenne J, Eschalier A. Serotonin receptor subtypes involved in the spinal antinociceptive effect of 5-HT in rats. Pain 2000;86:11-18
204. Hentall ID, Andresen MJ, Taguchi K. Serotonergic, cholinergic and nociceptive inhibition or excitation of raphe magnus neurons in barbiturate-anesthetized rats. Neuroscience 1993;52:303-10
205. Zhang L. Effects of 5-hydroxytryptamine on cat spinal motoneurons. Can J Physiol Pharmacol 1991;69:154-63
206. Dringenberg HC. Serotonergic receptor antagonists alter responses to general anaesthetics in rats. Br J Anaesth 2000;85:904-6
207. Doherty TJ, McDonell WN, Dyson DH, Black WD, Valliant AE. The effect of a 5-hydroxytryptamine antagonist (R51703) on halothane MAC in the dog. J Vet Pharmacol Ther 1995;18:153-5
208. Zhang Y, Laster MJ, Eger EI II, Stabernack CR, Sonner JM. Blockade of 5-HT2A receptors may mediate or modulate part of the immobility produced by inhaled anesthetics. Anesth Analg 2003;97:475-9
209. Johnston RR, Way WL, Miller RD. The effect of CNS catecholamine-depleting drugs on dextroamphetamine-induced elevation of halothane MAC. Anesthesiology 1974;41:57-61
210. Rampil IJ, Laster MJ, Eger EI II. Ondansetron does not alter isoflurane MAC in rats. Anesthesiology 2001;95:562-4
211. Eger EI II. Dragons and other scientific hazards. Anesthesiology 1979;50:1
212. Fernandez FR, Mehaffey WH, Turner RW. Dendritic Na- current inactivation can increase cell excitability by delaying a somatic depolarizing afterpotential. J Neurophysiol 2005;94: 3836-48
213. Eckenhoff RG, Johansson JS. On the relevance of "clinically relevant concentrations" of inhaled anesthetics in in vitr. experiments. Anesthesiology 1999;91:856-60
214. Zhang Y, Laster MJ, Eger EI II, Sharma M, Sonner JM. Lidocaine, MK-801, and MAC. Anesth Analg 2007;104: 1098-102
215. Linde HW, Lamb VE, Quimby CW Jr, Homi J, Eckenhoff JE. The search for better anesthetic agents: clinical investigation of ethrane. Anesthesiology 1970;32:555-9
216. Jaaskelainen SK, Kaisti K, Suni L, Hinkka S, Scheinin H. Sevoflurane is epileptogenic in healthy subjects at surgical levels of anesthesia. Neurology 2003;61:1073-8
217. Liu PL, Feldman HS, Giasi R, Patterson MK, Covino BG. Comparative CNS toxicity of lidocaine, etidocaine, bupivacaine, and tetracaine in awake dogs following rapid intravenous administration. Anesth Analg 1983;62:375-79
218. Zhang Y, Sharma M, Eger EI, II, Laster MJ, Hemmings HC Jr, Harris RA. Intrathecal veratridine administration increases MAC in rats. Anesth Analg 2008;107:875-8
219. Rehberg B, Xiao YH, Duch DS. Central nervous system sodium channels are significantly suppressed at clinical concentrations of volatile anesthetics. Anesthesiology 1996;84:1223-33
220. Stadnicka A, Kwok WM, Hartmann HA, Bosnjak ZJ. Effects of halothane and isoflurane on fast and slow inactivation of human heart hH1a sodium channels. Anesthesiology 1999;90: 1671-83
221. Shiraishi M, Harris RA. Effects of alcohols and anesthetics on recombinant voltage-gated Na- channels. J Pharmacol Exp Ther 2004;309:987-94
222. OuYang W, Hemmings HC Jr. Isoform-selective effects of isoflurane on voltage-gated Na- channels. Anesthesiology 2007;107:91-8
223. Schlame M, Hemmings HC Jr. Inhibition by volatile anesthetics of endogenous glutamate release from synaptosomes by a presynaptic mechanism. Anesthesiology 1995;82:1406-16
224. Ouyang W, Wang G, Hemmings HC Jr. Isoflurane and propofol inhibit voltage-gated sodium channels in isolated rat neurohypophysial nerve terminals. Mol Pharmacol 2003;64:373-81
225. Ratnakumari L, Vysotskaya TN, Duch DS, Hemmings HC Jr. Differential effects of anesthetic and nonanesthetic cyclobutanes on neuronal voltage-gated sodium channels. Anesthesiology 2000;92:529-41
226. Kendig JJ. Barbiturates: active form and site of action at node of Ranvier sodium channels. J Pharmacol Exp Ther 1981;218: 175-81
227. Mohr JT, Gribble GW, Lin SS, Eckenhoff RG, Cantor RS. Anesthetic potency of two novel synthetic polyhydric alkanols longer than the n-alkanol cutoff: evidence for a bilayermediated mechanism of anesthesia? J Med Chem 2005;48: 4172-6
228. Curry S, Moss GWJ, Dickinson R, Lieb WR, Franks NP. Probing the molecular dimensions of general anaesthetic target sites in tadpoles (Xenopus laevi.) and model systems using cycloalcohols. Br J Pharmacol 1991;102:167-73
229. Franks N, Lieb W. Partitioning of long-chain alcohols into lipid bilayers: implications for mechanisms of general anesthesia. Proc Natl Acad Sci USA 1986;83:5116-20
230. Cantor RS. The lateral pressure profile in membranes: a physical mechanism of general anesthesia. Biochemistry 1997;36:2339-44
231. Roth R, Gillespie D, Nonner W, Eisenberg B. Bubbles, Gating, and Anesthetics in Ion Channels. Biophys J 2008;94:4282-98