Inhaled anesthetics and immobility: Mechanisms, mysteries, and minimum alveolar anesthetic concentration

Anesthesia and Analgesia

Volumn 97, Issue 3, 2003, Pages 718-740

  Sonner, James M ^a   Antognini, Joseph F ^b   Dutton, Robert C ^a   Flood, Pamela ^c   Gray, Andrew T ^a   Harris, R Adron ^d   Homanics, Gregg E ^e   Kendig, Joan ^f   Orser, Beverley ^g   Raines, Douglas E ^h   Trudell, James ^f   Vissel, Bryce ⁱ   Eger III, Edmond I ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c University of Texas ^*  (United States)

^d UNIVERSITY OF TEXAS AT AUSTIN   (United States)

^e UNIVERSITY OF PITTSBURGH   (United States)

^f STANFORD UNIVERSITY   (United States)

^g UNIVERSITY OF TORONTO   (Canada)

^h HARVARD MEDICAL SCHOOL   (United States)

ⁱ GARVAN INSTITUTE OF MEDICAL RESEARCH   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

4 AMINOBUTYRIC ACID A RECEPTOR; ALPHA 2 ADRENERGIC RECEPTOR; CHOLINERGIC RECEPTOR; GLYCINE RECEPTOR; HALOTHANE; INHALATION ANESTHETIC AGENT; ION CHANNEL; ISOFLURANE; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; OPIATE RECEPTOR; POTASSIUM CHANNEL; POTASSIUM ION; SEROTONIN 3 RECEPTOR; SODIUM CHANNEL; SODIUM ION; VOLTAGE GATED CHANNEL FORMING PROTEIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; CHANNEL GATING; DRUG BINDING SITE; DRUG MECHANISM; GENETIC ENGINEERING; IMMOBILIZATION; INHALATION ANESTHESIA; MINIMUM LUNG ALVEOLUS CONCENTRATION; MOLECULAR MODEL; NEUROPHYSIOLOGY; PHARMACOLOGY; PRIORITY JOURNAL; REVIEW; SPINAL CORD; VOLTAGE CLAMP;

EID: 0041375505     PISSN: 00032999     EISSN: None     Source Type: Journal    
DOI: 10.1213/01.ANE.0000081063.76651.33     Document Type: Review

References (233)

1. Jurd R, Arras M, Lambert S, et al. General anesthetic actions in vivo strongly attenuated by a point mutation in the GABA(A) receptor beta3 subunit. FASEB J 2003;17:250-2.
2. Merkel G, Eger EI II. A comparative study of halothane and halopropane anesthesia: including a method for determining equipotency. Anesthesiology 1963;24:346-57.
3. Overton E. Studien über die Narkose, Zugleich ein Beitrag zur allgemeinen Pharmakologie. Jena, Germany: Gustav Fischer, 1901:1-195.
4. Meyer HH. Theorie der Alkoholnarkose. Arch Exp Pathol Pharmakol 1899;42:109-18.
5. Koblin DD, Chortkoff BS, Laster MJ, et al. Polyhalogenated and perfluorinated compounds that disobey the Meyer-Overton hypothesis. Anesth Analg 1994;79:1043-8.
6. Taheri S, Halsey MJ, Liu J, et al. What solvent best represents the site of action of inhaled anesthetics in humans, rats and dogs? Anesth Analg 1991;72:627-34.
7. Gonsowski CT, Eger EI II. Nitrous oxide minimum alveolar anesthetic concentration in rats is greater than previously reported. Anesth Analg 1994;79:710-2.
8. Fang Z, Sonner J, Laster MJ, et al. Anesthetic and convulsant properties of aromatic compounds and cycloalkanes: implications for mechanisms of narcosis. Anesth Analg 1996;83:1097-104.
9. Koblin DD, Fang Z, Eger EI II, et al. Minimum alveolar concentrations (MACs) of noble gases, nitrogen, and sulfur hexafluoride in rats: helium and neon as nonimmobilizers (nonanesthetics). Anesth Analg 1998;87:419-24.
10. Trudell JR. A unitary theory of anesthesia based on lateral phase separations in nerve membranes. Anesthesiology 1977;46:5-10.
11. Rosenberg PH, Jansson SE, Gripenberg J. Effects of halothane, thiopental, and lidocaine on fluidity of synaptic plasma membranes and artificial phospholipid membranes. Anesthesiology 1977;46:322-6.
12. Ueda I, Shieh DD, Eyring H. Anesthetic interaction with a model cell membrane: expansion, phase transition, and melting of the lecithin monolayer. Anesthesiology 1974;41:217-25.
13. Trudell JR, Hubbell WL, Cohen EN. The effect of two inhalation anesthetics on the order of spin-labeled phospholipid vesicles. Biochim Biophys Acta 1973;291:321-7.
14. Miller KW, Pang K-YY. General anaesthetics can selectively perturb lipid bilayer membranes. Nature 1976;263:253-5.
15. 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.
16. Fang ZX, Ionescu P, Chortkoff BS, et al. Anesthetic potencies of n-alkanols: results of additivity studies suggest a mechanism of action similar to that for conventional inhaled anesthetics. Anesth Analg 1997;84:1042-8.
17. Cromwell TH, Eger EI II, Stevens WC, Dolan WM. Forane uptake, excretion and blood solubility in man. Anesthesiology 1971;35:401-8.
18. White PF, Johnston RR, Eger EI II. Determination of anesthetic requirement in rats. Anesthesiology 1974;40:52-7.
19. Vitez TS, White PF, Eger EI II. Effects of hypothermia on halothane MAC and isoflurane MAC in the rat. Anesthesiology 1974;41:80-1.
20. Strum DP, Eger EI II. Partition coefficients for sevoflurane in human blood, saline, and olive oil. Anesth Analg 1987;66:654-6.
21. Kashimoto S, Furuya A, Nonaka A, et al. The minimum alveolar concentration of sevoflurane in rats. Eur J Anaesthesiol 1997;14:359-61.
22. Crawford M, Lerman J, Saldivia V, Carmichael F. Hemodynamic and organ blood flow responses to halothane and sevoflurane anesthesia during spontaneous ventilation. Anesth Analg 1992;75:1000-6.
23. Franks NP, Lieb WR. Do general anaesthetics act by competitive binding to specific receptors? Nature 1984;310:599-601.
24. Perouansky M, Kirson ED, Yaari Y. Presynaptic and postsynaptic actions of halothane at glutamatergic synapses in the mouse hippocampus. Br J Pharmacol 1996;124:1607-14.
25. Perouansky M, Kirson ED, Yaari Y. Mechanism of action of volatile anesthetics: effects of halothane on glutamate receptors in vitro. Toxicol Lett 1998;100-1:65-9.
26. MacIver MB. General anesthetic actions on transmission at glutamate and GABA synapses. In: Biebuyck JF, Lynch C III, Maze M, et al., eds. Anesthesia: biological foundations. New York: Lippincott-Raven, 1997:277-86.
27. Pashkov VN, Westphalen RI, Hemmings HC Jr. General anesthetics do not affect release of the neuropeptide cholecystokinin from isolated rat cortical nerve terminals. Anesthesiology 2002;97:1500-6.
28. Antognini JF, Schwartz K. Exaggerated anesthetic requirements in the preferentially anesthetized brain. Anesthesiology 1993;79:1244-9.
29. Antognini JF, Carstens E, Atherley R. Does the immobilizing effect of thiopental in brain exceed that of halothane? Anesthesiology 2002;96:980-6.
30. Borges M, Antognini JF. Does the brain influence somatic responses to noxious stimuli during isoflurane anesthesia? Anesthesiology 1994;81:1511-5.
31. Rampil IJ, Mason P, Singh H. Anesthetic potency (MAC) is independent of forebrain structures in the rat. Anesthesiology 1993;78:707-12.
32. Rampil IJ. Anesthetic potency is not altered after hypothermic spinal cord transection in rats. Anesthesiology 1994;80:606-10.
33. Rampil IJ, Laster MJ. No correlation between quantitative electroencephalographic measurements and movement response to noxious stimuli during isoflurane anesthesia in rats. Anesthesiology 1992;77:920-5.
34. Jinks SL, Martin JT, Carstens E, et al. Peri-MAC depression of a nociceptive withdrawal reflex is accompanied by reduced dorsal horn activity with halothane but not isoflurane. Anesthesiology 2003;98:1128-38.
35. King BS, Rampil IJ. Anesthetic depression of spinal motor neurons may contribute to lack of movement in response to noxious stimuli. Anesthesiology 1994;81:1484-92.
36. Rampil IJ, King BS. Volatile anesthetics depress spinal motor neurons. Anesthesiology 1996;85:129-34.
37. Zhou HH, Jin TT, Qin B, Turndorf H. Suppression of spinal cord motoneuron excitability correlates with surgical immobility during isoflurane anesthesia. Anesthesiology 1998;88:955-61.
38. Kendig JJ, Kodde A, Gibbs LM, et al. Correlates of anesthetic properties in isolated spinal cord: cyclobutanes. Eur J Pharmacol 1994;264:427-36.
39. Savola MK, Woodley SJ, Maze M, Kendig JJ. Isoflurane and an alpha2-adrenoceptor agonist suppress nociceptive neurotransmission in neonatal rat spinal cord. Anesthesiology 1991;75:489-98.
40. Wong SME, Fong E, Tauck DL, Kendig JJ. Ethanol as a general anesthetic: actions in spinal cord. Eur J Pharmacol 1997;329:121-7.
41. Wong SME, Cheng G, Homanics G, Kendig JJ. Enflurane actions on spinal cords from mice that lack the beta3 subunit of the GABA(A) receptor. Anesthesiology 2001;95:154-64.
42. 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.
43. Eger EI II, Zhang Y, Laster MJ, et al. Acetylcholine receptors do not mediate the immobilization produced by inhaled anesthetics. Anesth Analg 2002;94:1500-4.
44. A or glycine receptors. J Pharmacol Exp Ther 1999;290:362-7.
45. A or glycine receptors. Anesthesiology 2000;93:1075-84.
46. Cheng G, Kendig JJ. Pre- and postsynaptic volatile anaesthetic actions on glycinergic transmission to spinal cord motor neurons. Br J Pharmacol 2002;136:673-84.
47. Cheng G, Kendig JJ. Enflurane decreases glutamate neurotransmission to spinal cord motor neurons by both pre- and postsynaptic actions. Anesth Analg 2003;96:1354-9.
48. Krasowski M, Jenkins A, Flood P, et al. General anesthetic potencies of a series of propofol analogs correlate with potency for potentiation of gamma-aminobutyric acid (GABA) current at the GABA(A) receptor but not with lipid solubility. J Pharmacol Exp Ther 2001;297:338-51.
49. Flood P, Krasowski MD. Intravenous anesthetics differentially modulate ligand-gated ion channels. Anesthesiology 2000;92:1418-25.
50. Stabernack C, Sonner JM, Laster M, et al. Spinal NMDA receptors may contribute to the immobilizing action of isoflurane. Anesth Analg 2003;96:102-7.
51. Minami K, Wick MJ, Stern-Bach Y, et al. Sites of volatile anesthetic action on kainate (glutamate receptor 6) receptors. J Biol Chem 1998;273:8248-55.
52. A receptor/chloride channel complex in anesthesia. Anesthesiology 1993;78:757-76.
53. A receptor subtypes. In: Bradley RJ, Harris RA, eds. International review of neurobiology. San Diego: Academic Press, 1995:95.
54. McKernan RM, Whiting PJ. Which GABAa-receptor subtypes really occur in the brain? Trends Neurosci 1996;19:139-43.
55. Sieghart W. Structure and pharmacology of gamma-aminobutyric acid A receptor subtypes. Pharmacol Rev 1995;47:181-234.
56. Rajendra S, Schofield PR. Molecular mechanisms of inherited startle syndromes. Trends Neurosci 1995;18:80-2.
57. Betz H. Glycine receptors: heterogenous and widespread in the mammalian brain. Trends Neurosci 1991;14:458-61.
58. Betz H. Ligand-gated ion channels in the brain: the amino acid receptor superfamily. Neuron 1990;5:383-92.
59. 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.
60. Downie DL, Hall AC, Lieb WR, Franks NP. Effects of inhalational general anaesthetics on native glycine receptors in rat medullary neurones and recombinant glycine receptors in Xenopus oocytes. Br J Pharmacol 1996;118:493-502.
61. 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.
62. Harrison NL, Kugler JL, Jones MV, et al. Positive modulation of human gamma-aminobutyric acid type A and glycine receptors by the inhalation anesthetic isoflurane. Mol Pharmacol 1993;44:628-32.
63. - current correlates with in vivo anesthetic potency. J Pharmacol Exp Ther 1994;270:987-91.
64. Mihic SJ, McQuilkin SJ, Eger EI II, et al. Potentiation of gamma-aminobutyric acid type A receptor-mediated chloride currents by novel halogenated compounds correlates with their abilities to induce general anesthesia. Mol Pharmacol 1994;46:851-7.
65. 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.
66. Minami K, Gereau RW, Minami M, et al. Effects of ethanol and anesthetics on type 1 and 5 metabotropic glutamate receptors expressed in Xenopus laevis oocytes. Mol Pharmacol 1998;53:148-56.
67. Mihic SJ, Harris RA. Inhibition of r1 receptor GABAergic currents by alcohol and volatile anesthetics. J Pharmacol Exp Ther 1996;277:411-6.
68. A and glycine receptors. Nature 1997;389:385-9.
69. A receptor alpha1 subunit: implications for modulation by inhaled anesthetics and ion channel structure. Neuropharmacology 2002;43:669-78.
70. A receptor. J Neurosci 2001;21:RC136.
71. Pohorille A, Cieplak P, Wilson MA. Interactions of anesthetics with the membrane-water interface. Chem Phys 1996;204:337-45.
72. 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.
73. Mascia MP, Gong D, Eger EI II, Harris RA. The anesthetic potency of propanol and butanol versus propanethiol and butanethiol in alpha1 wild type and alpha1(S267Q) glycine receptors. Anesth Analg 2000;91:1289-93.
74. Mascia MP, Trudell JR, Harris RA. Specific binding sites for alcohols and anesthetics on ligand-gated ion channels. Proc Natl Acad Sci U S A 2000;97:9305-10.
75. Sanna E, Murgia A, Casula A, Biggio G. Differential subunit dependence of the actions of the general anesthetics alphaxalone and etomidate at gamma-aminobutyric acid type A receptors expressed in Xenopus laevis oocytes. Mol Pharmacol 1997;51:484-90.
76. Johnson JW, Ascher P. Glycine potentiates the NMDA response in cultured mouse brain neurons. Nature 1987;325:529-31.
77. Meguro H, Mori H, Araki K, et al. Functional characterization of a heteromeric NMDA receptor channel expressed from cloned cDNAs. Nature 1992;357:70-4.
78. Monyer H, Sprengel R, Schoepfer R, et al. Heteromeric NMDA receptors: molecular and functional distinction of subtypes. Science 1992;256:1217-21.
79. Chatterton J, Awobuluyi M, Premkumar LS, et al. Excitatory glycine receptors containing the NR3 family of NMDA receptor subunits. Nature 2002;415:793-8.
80. Mori H, Mishina M. Structure and function of the NMDA receptor channel. Neuropharmacology 1995;34:1219-37.
81. Ciabarra AM, Sullivan JM, Gahn LG, et al. Cloning and characterization of chi-1: a developmentally regulated member of a novel class of the ionotropic glutamate receptor family. J Neurosci 1995;15:6498-508.
82. Sucher NJ, Akbarian S, Chi CL, et al. Developmental and regional expression pattern of a novel NMDA receptor-like subunit (NMDAR-L) in the rodent brain. J Neurosci 1995;15:6509-20.
83. Hollmann MW, Liu HT, Hoenemann CW, et al. Modulation of NMDA receptor function by ketamine and magnesium. II. Interactions with volatile anesthetics. Anesth Analg 2001;92:1182-91.
84. Lin LH, Chen LL, Harris RA. Enflurane inhibits NMDA, AMPA, and kainate-induced currents in Xenopus oocytes expressing mouse and human brain mRNA. FASEB J 1993;7:479-85.
85. 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.
86. Hara K, Harris RA. The anesthetic mechanism of urethane: the effects on neurotransmitter-gated ion channels. Anesth Analg 2002;94:313-8.
87. 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.
88. McKernan RM, Rosahl TW, Reynolds DS, et al. Sedative but not anxiolytic properties of benzodiazepines are mediated by the GABA(A) receptor alpha1 subtype. Nat Neurosci 2000;3:587-92.
89. Rudolph U, Crestani F, Benke D, et al. Benzodiazepine actions mediated by specific gamma-aminobutyric acid(A) receptor subtypes. Nature 1999;401:796-800.
90. A receptor beta3 subunit. FASEB J 2003;17:250-2.
91. Homanics GE. Knockout and knockin mice. In: Liu Y, Lovinger DM, eds. Methods for alcohol-related neuroscience research. Boca Raton, FL: CRC Press, 2002:31-60.
92. Tsein JZ, Huerta PT, Tonegawa S. The essential role of hippocampal CA1 NMDA receptor-dependent synaptic plasticity in spatial memory. Cell 1996;87:1327-38.
93. Rudolph U, Crestani F, Mohler H. GABA(A) receptor subtypes: dissecting their pharmacological functions. Trends Pharmacol Sci 2001;22:188-94.
94. Harrison NL, Homanics GE. Production and characterization of knockin mice containing a serine to histidine mutation at position 270 of the alpha 1 subunit of the GABAa receptor [abstract]. Alcohol Clin Exp Res 2001;25:A38.
95. Sonner JM, Zhang Y, Stabernack C, et al. 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.
96. 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.
97. Zhang Y, Laster MJ, Hara K, et al. Glycine receptors may mediate part of the immobility produced by inhaled anesthetics. Anesth Analg 2003;96:97-101.
98. Zhang Y, Sonner JM, Eger EI II, et al. GABAA receptors do not mediate the immobility produced by inhaled anesthetics. Anesth Analg. In press.
99. Kingsmore S, Giros B, Suh D, et al. Glycine receptor beta-subunit gene mutation in spastic mouse associated with LINE-1 element insertion. Nat Genet 1994;7:136-41.
100. Quinlan JJ, Ferguson C, Jester K, et al. Mice with glycine receptor subunit mutations are both sensitive and resistant to volatile anesthetics. Anesth Analg 2002;95:578-82.
101. Ryan SG, Buckwalter MS, Lynch JW, et al. 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.
102. Quinlan JJ, Homanics GE, Firestone LL. Anesthesia sensitivity in mice that lack the beta3 subunit of the gamma-aminobutyric acid type A receptor. Anesthesiology 1998;88:775-80.
103. Eger EI II, Ionescu P, Laster MJ, et al. MAC of fluorinated alkanols in rats: relevance to theories of narcosis. Anesth Analg 1999;88:867-76.
104. 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.
105. - currents in cultured rat hippocampal neurones by three volatile anaesthetics. J Physiol (Lond) 1992;449:279-93.
106. + current. Nature 1988;333:662-4.
107. + channel. Anesthesiology 1998;88:1076-84.
108. + channels. Nat Neurosci 1999;2:422-6.
109. Sirois JE, Lynch C III, Bayliss DA. Convergent and reciprocal modulation of a leak K(+) current and I(h) by an inhalational anaesthetic and neurotransmitters in rat brainstem motoneurones. J Physiol 2002;541:717-29.
110. Yost CS. Tandem pore domain K channels: an important site of volatile anesthetic action? Curr Drug Targets 2000;1:207-17.
111. Gerstin KM, Gong DH, Abdallah M, et al. Mutation of KCNK5 or Kir3.2 potassium channels in mice does not change minimum alveolar anesthetic concentration. Anesth Analg 2003;96:1345-9.
112. Machu TK, Harris RA. Alcohols and anesthetics enhance the function of 5-hydroxytryptamine3 receptors expressed in Xenopus laevis oocytes. J Pharmacol Exp Ther 1994;271:898-905.
113. Suzuki T, Koyama H, Sugimoto M, et al. The diverse actions of volatile and gaseous anesthetics on human-cloned 5-hydroxytryptamine3 receptors expressed in Xenopus oocytes. Anesthesiology 2002;96:699-704.
114. Rampil IJ, Laster MJ, Eger EI II. Ondansetron does not alter isoflurane MAC in rats. Anesthesiology 2001;95:562-4.
115. Lysko GS, Robinson JL, Casto R, Ferrone RA. The stereospecific effects of isoflurane isomers in vivo. Eur J Pharmacol 1994;263:25-9.
116. Franks NP, Lieb WR. Stereospecific effects of inhalational general anesthetic optical isomers on nerve ion channels. Science 1991;254:427-30.
117. 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.
118. Raines DE, Claycomb RJ, Forman SA. Nonhalogenated anesthetic alkanes and perhalogenated nonimmobilizing alkanes inhibit alpha4beta2 neuronal nicotinic acetylcholine receptors. Anesth Analg 2002;95:573-7.
119. Boulter J, Hollmann M, O'Shea-Greenfield A, et al. Molecular cloning and functional expression of glutamate receptor subunit genes. Science 1990;31:1033-7.
120. Hollmann M, Heinemann S. Cloned glutamate receptors. Annu Rev Neurosci 1994;17:31-108.
121. Martin DC, Plagenhoef M, Abraham J, et al. Volatile anesthetics and glutamate activation of N-methyl-D-aspartate receptors. Biochem Pharmacol 1995;49:809-17.
122. 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.
123. Masaki E, Yamazaki K, Ohno Y, et al. The anesthetic interaction between adenosine triphosphate and N-methyl-D-aspartate receptor antagonists in the rat. Anesth Analg 2001;92:134-9.
124. Ishizaki K, Yoon DM, Yoshida N, et al. Intrathecal administration of N-methyl-D-aspartate receptor antagonist reduces the minimum alveolar anaesthetic concentration of isoflurane in rats. Br J Anaesth 1995;75:636-8.
125. Ishizaki K, Yoshida N, Yoon DM, et al. Intrathecally administered NMDA receptor antagonists reduce the MAC of isoflurane in rats. Can J Anaesth 1996;43:724-30.
126. 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.
127. Dutton RC, Zhang Y, Stabernack CR, et al. Temporal summation governs part of the minimum alveolar concentration of isoflurane anesthesia. Anesthesiology 2003;98:1372-7.
128. Woolf CJ, Thompson SWN. The induction and maintenance of central sensitization is dependent on N-methyl-D-aspartic acid receptor activation: implications for the treatment of post-injury pain hypersensitivity states. Pain 1991;44:293-9.
129. 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.
130. McFarlane C, Warner DS, Todd MM, Nordholm L. AMPA receptor competitive antagonism reduces halothane MAC in rats. Anesthesiology 1992;77:1165-70.
131. Ishizaki K, Sasaki M, Karasawa S, et al. Intrathecal co-administration of NMDA antagonist and NK-1 antagonist reduces MAC of isoflurane in rats. Acta Anaesthesiol Scand 1999;43:753-9.
132. Carla V, Moroni F. General anaesthetics inhibit the responses induced by glutamate receptor agonists in the mouse cortex. Neurosci Lett 1992;146:21-4.
133. Joo DT, Gong D, Sonner JM, et al. 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.
134. 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.
135. Orser BA, Joo DT, Zhu G, et al. Increased desensitization of AMPA receptors may cause hypersensitivity to anesthetics in GluT2 null mutant mice. In: Urban BW, Barann M, eds. Molecular and basic mechanisms of anesthetics. Lengerich, Germany: Pabst Science Publishers. In press.
136. Bar-Peled O, O'Brien RJ, Morrison JH, Rothstein JD. Cultured motor neurons possess calcium-permeable AMPA/kainate receptors. Neuroreport 1999;10:855-9.
137. Van Damme P, Van Den Bosch L, Van Houtte E, et al. GluR2-dependent properties of AMPA receptors determine the selective vulnerability of motor neurons to excitotoxicity. J Neurophysiol 2002;88:1279-87.
138. 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.
139. Dingledine R, Borges K, Bowie D, Traynelis SF. The glutamate receptor ion channels. Pharmacol Rev 1999;51:7-61.
140. Vissel B, Royle GA, Christie BR, et al. The role of RNA editing of kainate receptors in synaptic plasticity and seizures. Neuron 2001;29:217-27.
141. Lingamaneni R, Birch ML, Hemmings HC Jr. Widespread inhibition of sodium channel-dependent glutamate release from isolated nerve terminals by isoflurane and propofol. Anesthesiology 2001;95:1460-6.
142. Himes RS Jr, DiFazio CA, Burney RG. Effects of lidocaine on the anesthetic requirements for nitrous oxide and halothane. Anesthesiology 1977;47:437-40.
143. DiFazio CA, Neiderlehner JR, Burney RG. The anesthetic potency of lidocaine in the rat. Anesth Analg 1976;55:818-21.
144. Himes RS Jr, Munson ES, Embro WJ. Enflurane requirement and ventilatory response to carbon dioxide during lidocaine infusion in dogs. Anesthesiology 1979;51:131-4.
145. Weigt HU, Kwok WM, Rehmert GC, Bosnjak ZJ. Modulation of the cardiac sodium current by inhalational anesthetics in the absence and presence of beta-stimulation. Anesthesiology 1998;88:114-24.
146. Irnaten M, Wang J, Chang KS, et al. Ketamine inhibits sodium currents in identified cardiac parasympathetic neurons in nucleus ambiguus. Anesthesiology 2002;96:659-66.
147. Asai T, Kusudo K, Ikeda H, et al. Effect of halothane on neuronal excitation in the superficial dorsal horn of rat spinal cord slices: evidence for a presynaptic action. Eur J Neurosci 2002;15:1278-90.
148. 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.
149. + channel in rat dorsal root ganglion neurons and their blockade by halothane. Eur J Neurosci 1998;10:2547-56.
150. Ratnakumari L, Hemmings HC Jr. Inhibition of presynaptic sodium channels by halothane. Anesthesiology 1998;88:1043-54.
151. Weigt H, Kwok WM, Rehmert GC, et al. Modulation of cardiac sodium current by alpha1-stimulation and volatile anesthetics. Anesthesiology 1997;87:1507-16.
152. + current. Anesthesiology 1997;87:1494-506.
153. Weigt HU, Kwok WM, Rehmert GC, et al. Voltage-dependent effects of volatile anesthetics on cardiac sodium current. Anesth Analg 1997;84:285-93.
154. Ries CR, Puil E. Mechanism of anesthesia revealed by shunting actions of isoflurane on thalamocortical neurons. J Neurophysiol 1999;81:1795-801.
155. Schwarz DW, Tennigkeit F, Adam T, et al. Membrane properties that shape the auditory code in three nuclei of the central nervous system. J Otolaryngol 1998;27:311-7.
156. 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.
157. 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.
158. Mounsey JP, Patel MK, Mistry D, et al. Protein kinase C co-expression and the effects of halothane on rat skeletal muscle sodium channels. Br J Pharmacol 1999;128:989-98.
159. Patel MK, Mistry D, John JE III, Mounsey JP. Sodium channel isoform-specific effects of halothane: protein kinase C co-expression and slow inactivation gating. Br J Pharmacol 2000;130:1785-92.
160. Siegelbaum SA, Schwartz JH, Kandel ER. Modulation of synaptic transmission: second messengers. In: Kandel ER, Schwartz JH, Jessell TM, eds. Principles of neural science. 4th ed. New York: McGraw-Hill, 2000.
161. Way WL, Hosobuchi Y, Johnson BH, Eger EI II. Anesthesia does not increase opioid peptides in cerebrospinal fluid of humans. Anesthesiology 1984;60:43-5.
162. 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.
163. Katoh T, Ikeda K. The effects of fentanyl on sevoflurane requirements for loss of consciousness and skin incision. Anesthesiology 1998;88:18-24.
164. Harper MH, Winter PM, Johnson BH, Eger EI II. Naloxone does not antagonize general anesthesia in the rat. Anesthesiology 1978;49:3-5.
165. Smith RA, Wilson M, Miller KW. Naloxone has no effect on nitrous oxide anesthesia. Anesthesiology 1978;49:6-8.
166. Segal IS, Vickery RG, Walton JK, et al. Dexmedetomidine diminishes halothane anesthetic requirements in rats through a postsynaptic alpha-2 adrenergic receptor. Anesthesiology 1988;69:818-23.
167. Rabin BC, Reid K, Guo TZ, et al. Sympatholytic and minimum anesthetic concentration-sparing responses are preserved in rats rendered tolerant to the hypnotic and analgesic action of dexmedetomidine, a selective alpha-2 adrenergic agonist. Anesthesiology 1996;85:565-73.
168. Bloor BC, Flacke WE. Reduction in halothane anesthetic requirement by clonidine, an alpha-adrenergic agonist. Anesth Analg 1982;61:741-5.
169. Vickery RG, Maze M. Action of the stereoisomers of medetomidine in halothane-anesthetized dogs. Acta Vet Scand Suppl 1989;85:71-6.
170. Ghinone M, Calvillo O, Quintin L. Anesthesia and hypertension: the effect of clonidine on perioperative hemodynamics and isoflurane requirements. Anesthesiology 1987;67:3-10.
171. Lawrence CJ, De Lange S. Effects of a single pre-operative dexmedetomidine dose on isoflurane requirements and perioperative haemodynamic stability. Anaesthesia 1997;52:736-44.
172. Aantaa R, Jaakola ML, Kallio A, Kanto J. Reduction of the minimum alveolar concentration of isoflurane by dexmedetomidine. Anesthesiology 1997;86:1055-60.
173. Kendig JJ, Savola MKT, Woodley SJ, Maze M. Alpha-2 adrenoceptors inhibit a nociceptive response in neonatal rat spinal cord. Eur J Pharmacol 1991;192:293-300.
174. Grabow TS, Hurley RW, Banfor PN, Hammond DL. Supraspinal and spinal delta(2) opioid receptor-mediated antinociceptive synergy is mediated by spinal alpha(2) adrenoceptors. Pain 1999;83:47-55.
175. Sabbe MB, Penning JP, Ozaki GT, Yaksh TL. Spinal and systemic action of the alpha 2 receptor agonist dexmedetomidine in dogs: antinociception and carbon dioxide response. Anesthesiology 1994;80:1057-72.
176. Sullivan AF, Kalso EA, McQuay HJ, Dickenson AH. The antinociceptive actions of dexmedetomidine on dorsal horn neuronal responses in the anaesthetized rat. Eur J Pharmacol 1992;215:127-33.
177. Eger EI II, Xing Y, Laster MJ, Sonner JM. Alpha-2 adrenoreceptors probably do not mediate the immobility produced by inhaled anesthetics. Anesth Analg 2003;96:1661-4.
178. Vonvoigtlander P, Lewis RA, Neff GL. Kappa opioid analgesia is dependent on serotonergic mechanisms. J Pharmacol Exp Ther 1984;231:270-4.
179. Kellstein DE, Malseed RT, Goldstein FJ. Opioid-monamine interactions in spinal antinociception: evidence for serotonin but not norepinephrine reciprocity. Pain 1988;34:85-92.
180. 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.
181. Kiefel JM, Paul D, Bodnar RJ. Reduction in opioid and non-opioid forms of swim analgesia by 5-HT2 receptor antagonists. Brain Res 1989;500:231-40.
182. Giordano J. Analgesic profile of centrally administered 2-methylserotonin against acute pain in rats. Eur J Pharmacol 1991;199:233-6.
183. 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 periaque-ductal gray. Behav Brain Res 1997;87:97-103.
184. 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.
185. Bardin L, Lavarenne J, Eschalier A. Serotonin receptor subtypes involved in the spinal antinociceptive effect of 5-HT in rats. Pain 2000;86:11-8.
186. 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.
187. Zhang L. Effects of 5-hydroxytryptamine on cat spinal motoneurons. Can J Physiol Pharmacol 1991;69:154-63.
188. Dringenberg HC. Serotonergic receptor antagonists alter responses to general anaesthetics in rats. Br J Anaesth 2000;85:904-6.
189. Doherty TJ, McDonell WN, Dyson DH, et al. The effect of a 5-hydroxytryptamine antagonist (R51703) on halothane MAC in the dog. J Vet Pharmacol Ther 1995;18:153-5.
190. Zhang Y, Laster MJ, Eger EI II, et al. Blockade of 5-HT2A receptors may mediate or modulate part of the immobility produced by inhaled anesthetics. Anesth Analg. In press.
191. Coggeshall RE, Carlton SM. Receptor localization in the mammalian dorsal horn and primary afferent neurons. Brain Res Brain Res Rev 1997;24:28-66.
192. Knangrga I, Jiang MC, Randic M. Actions of (-)-baclofen on rat dorsal horn neurons. Brain Res 1991;562:265-75.
193. Dirig DM, Yaksh TL. Intrathecal baclofen and muscimol, but not midazolam, are antinociceptive using the rat-formalin model. J Pharmacol Exp Ther 1995;275:219-27.
194. Dickenson AH, Brewer CM, Hayes NA. Effects of topical baclofen on C fiber-evoked neuronal activity in the rat dorsal horn. Neurosci Biobehav Rev 1985;14:557-62.
195. Albright AL, Cervi A, Singletary J. Intrathecal baclofen for spasticity in cerebral palsy. JAMA 1991;265:1418-22.
196. Mason P, Owens CA, Hammond DL. Antagonism of the antinocifensive action of halothane by intrathecal administration of GABAA receptor antagonists. Anesthesiology 1996;84:1205-14.
197. Weng HR, Mansikka H, Winchurch R, et al. Sensory processing in the deep spinal dorsal horn of neurokinin-1 receptor knockout mice. Anesthesiology 2001;94:1105-12.
198. Sivilotti LG, Thompson SW, Woolf SJ. Rate of rise of the cumulative depolarization evoked by repetitive stimulation of small-caliber afferents is a predictor of action potential windup in rat spinal neurons in vitro. J Neurophysiol 1993;69:1621-31.
199. Ishizaki K, Karasawa S, Takahashi K, et al. Intrathecal neurokinin-1 receptor antagonist reduces isoflurane MAC in rats. Can J Anaesth 1997;44:543-9.
200. Beckstead MJ, Phelan R, Trudell JR, et al. Anesthetic and ethanol effects on spontaneously opening glycine receptor channels. J Neurochem 2002;82:1343-51.
201. Yamakura T, Bertaccini E, Trudell JR, Harris RA. Anesthetics and ion channels: molecular models and sites of anesthetic action. Annu Rev Pharmacol Toxicol 2001;41:23-51.
202. Scheller M, Forman SA. The gamma subunit determines whether anesthetic-induced leftward shift is altered by a mutation at alpha1S270 in alpha1beta2gamma2L GABA(A) receptors. Anesthesiology 2001;95:123-31.
203. 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.
204. Trudell JR. Unique assignment of inter-subunit association in GABAa alpha1 beta3 gamma2 receptors determined by molecular modeling. Biochim Biophys Acta 2002;1565:91-6.
205. A receptor. Nature 2003;421:421-5.
206. Bertaccini E, Trudell JR. Predicting the transmembrane secondary structure of ligand-gated ion channels. Protein Eng 2002;15:443-53.
207. Unwin N, Miyazawa A, Li J, Fujiyoshi Y. Activation of the nicotinic acetylcholine receptor involves a switch in conformation of the alpha subunits. J Mol Biol 2002;319:1165-76.
208. Trudell JR, Bertaccini E. Molecular modelling of specific and non-specific anaesthetic interactions. Br J Anaesth 2002;89:32-40.
209. Chang G, Spencer RH, Lee AT, et al. Structure of the MscL homolog from mycobacterium tuberculosis: a gated mechano-sensitive ion channel. Science 1998;282:2220-6.
210. Johansson JS, Scharf D, Davies LA, et al. A designed four-alpha-helix bundle that binds the volatile general anesthetic halothane with high affinity. Biophys J 2000;78:982-93.
211. Tanner JW, Johansson JS, Liebman PA, Eckenhoff RG. Predictability of weak binding from X-ray crystallography: inhaled anesthetics and myoglobin. Biochemistry 2001;40:5075-80.
212. Wilson GG, Pascual JM, Brooijmans N, et al. The intrinsic electrostatic potential and the intermediate ring of charge in the acetylcholine receptor channel. J Gen Physiol 2000;115:93-106.
213. Scheller M, Forman SA. Coupled and uncoupled gating and desensitization effects by pore domain mutations in GABA(A) receptors. J Neurosci 2002;22:8411-21.
214. Ionescu P, Eger EI II, Trudell J. Direct determination of oil/ saline partition coefficients. Anesth Analg 1994;79:1056-8.
215. Karplus M, McCammon JA. Molecular dynamics simulations of biomolecules. Nat Struct Biol 2002;9:646-52.
216. Koubi L, Tarek M, Bandyopadhyay S, et al. Effects of the nonimmobilizer hexafluroethane on the model membrane dimyristoylphosphatidylcholine. Anesthesiology 2002;97:848-55.
217. Johansson JS, Scharf D. Towards an understanding of how general anesthetics alter central nervous system protein function. Reg Anesth Pain Med 2001;26:267-70.
218. Sukharev S, Durell SR, Guy HR. Structural models of the MscL gating mechanism. Biophys J 2001;81:917-36.
219. Tang P, Mandal PK, Xu Y. NMR structures of the second transmembrane domain of the human glycine receptor alpha(1) subunit: model of pore architecture and channel gating. Biophys J 2002;83:252-62.
220. Law RJ, Forrest LR, Ranatunga KM, et al. Structure and dynamics of the pore-lining helix of the nicotinic receptor: MD simulations in water, lipid bilayers, and transbilayer bundles. Proteins 2000;39:47-55.
221. Opella SJ, Marassi FM, Gesell JJ, et al. Structures of the M2 channel-lining segments from nicotinic acetylcholine and NMDA receptors by NMR spectroscopy. Nat Struct Biol 1999;6:374-9.
222. + conduction and selectivity. Science 1998;280:69-77.
223. + channel: electrostatic stabilization of monovalent cations. Science 1999;285:100-2.
224. Aqvist J, Luzhkov V. Ion permeation mechanism of the potassium channel. Nature 2000;404:881-4.
225. Eger EI II, Halsey MJ, Harris RA, et al. Hypothesis: volatile anesthetics produce immobility by acting on two sites approximately five carbons apart. Anesth Analg 1999;88:1395-400.
226. Pauling L. The nature of the chemical bond. 3rd ed. Ithaca, NY: Cornell University Press, 1960:499.
227. Bormann J, Hamill OP, Sakmann B. Mechanism of anion permeation through channels gated by glycine and gamma-aminobutyric acid in mouse cultured spinal neurons. J Physiol 1987;385:243-86.
228. Eger EI II, Fisher DM, Dilger JP, et al. Relevant concentrations of inhaled anesthetics for in vitro studies of anesthetic mechanisms. Anesthesiology 2001;94:915-21.
229. Cantor RS. Breaking the Meyer-Overton rule: predicted effects of varying stiffness and interfacial activity on the intrinsic potency of anesthetics. Biophys J 2001;80:2284-97.
230. Cantor RS. The lateral pressure profile in membranes: a physical mechanism of general anesthesia. Biochemistry 1997;36:2339-44.
231. Cantor RS. Lateral pressures in cell membranes: a mechanism for modulation of protein function. J Phys Chem B 1997;101:1723-5.
232. Cantor RS. Solute modulation of conformational equilibria in intrinsic membrane proteins: apparent "cooperativity" without binding. Biophys J 1999;77:2643-7.
233. Tang P, Xu Y. Large-scale molecular dynamics simulations of general anesthetic effects on the ion channel in the fully hydrated membrane: the implication of molecular mechanisms of general anesthesia. Proc Natl Acad Sci U S A 2002;99:16035-40.