Mechanisms of actions of inhaled anesthetics.

“Suffering so great as I underwent cannot be expressed in words . . . but the blank whirlwind of emotion, the horror of great darkness, and the sense of desertion by God and man, which swept through my mind, and overwhelmed my heart, I can never forget.”1 Such was the experience of surgery before October 1846, when William Morton's successful public demonstration of ether anesthesia at Massachusetts General Hospital led to its widespread acceptance by surgeons. Today, anesthesiologists employ a wide variety of drugs, some of which they use exclusively to produce general anesthesia.2,3 This review focuses on the . . .

[1]  B. Antkowiak,et al.  General anesthetic actions in vivo strongly attenuated by a point mutation in the GABAA receptor β3 subunit , 2003, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[2]  T. Guo,et al.  The sedative component of anesthesia is mediated by GABAA receptors in an endogenous sleep pathway , 2002, Nature Neuroscience.

[3]  D. Raines,et al.  Nonhalogenated Anesthetic Alkanes and Perhalogenated Nonimmobilizing Alkanes Inhibit α4β2 Neuronal Nicotinic Acetylcholine Receptors , 2002 .

[4]  B. Antkowiak.  In vitro networks: cortical mechanisms of anaesthetic action. , 2002, British journal of anaesthesia.

[5]  C. Schwarzbauer,et al.  In vivo imaging of anaesthetic action in humans: approaches with positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). , 2002, British journal of anaesthesia.

[6]  K. Miller,et al.  The nature of sites of general anaesthetic action. , 2002, British journal of anaesthesia.

[7]  H. Nash.  In vivo genetics of anaesthetic action. , 2002, British journal of anaesthesia.

[8]  M. Bleckwenn,et al.  Concepts and correlations relevant to general anaesthesia. , 2002, British journal of anaesthesia.

[9]  J. Kendig,et al.  In vitro networks: subcortical mechanisms of anaesthetic action. , 2002, British journal of anaesthesia.

[10]  J. Antognini,et al.  In vivo characterization of clinical anaesthesia and its components. , 2002, British journal of anaesthesia.

[11]  C. Vahle-hinz,et al.  What can in vivo electrophysiology in animal models tell us about mechanisms of anaesthesia? , 2002, British journal of anaesthesia.

[12]  W. Hevers,et al.  Altered receptor subtypes in the forebrain of GABAA receptor δ subunit-deficient mice: recruitment of γ2 subunits , 2002, Neuroscience.

[13]  R. Eckenhoff.  Promiscuous ligands and attractive cavities: how do the inhaled anesthetics work? , 2001, Molecular interventions.

[14]  Z. Bosnjak,et al.  Anesthetic Effects on Mitochondrial ATP-sensitive K Channel , 2001, Anesthesiology.

[15]  H. Hemmings,et al.  Widespread Inhibition of Sodium Channel–dependent Glutamate Release from Isolated Nerve Terminals by Isoflurane and Propofol , 2001, Anesthesiology.

[16]  R. Rossaint,et al.  Effects of the Anesthetic Gases Xenon, Halothane, and Isoflurane on Calcium and Potassium Currents in Human Atrial Cardiomyocytes , 2001, Anesthesiology.

[17]  V. Feshchenko,et al.  Drug-induced Amnesia Is a Separate Phenomenon from Sedation: Electrophysiologic Evidence , 2001, Anesthesiology.

[18]  E. Honoré,et al.  Anesthetic-sensitive 2P Domain K+ Channels , 2001, Anesthesiology.

[19]  M. Mintun,et al.  Dose-dependent Enhancement of In Vivo GABAA–Benzodiazepine Receptor Binding by Isoflurane , 2001, Anesthesiology.

[20]  D. Raines,et al.  Nonhalogenated Alkane Anesthetics Fail to Potentiate Agonist Actions on Two Ligand-gated Ion Channels , 2001, Anesthesiology.

[21]  E. Kayser,et al.  Mitochondrial mutations differentially affect aging, mutability and anesthetic sensitivity in Caenorhabditis elegans , 2001, Mechanisms of Ageing and Development.

[22]  Astrid G. Stucke,et al.  Effects of Sevoflurane on Excitatory Neurotransmission to Medullary Expiratory Neurons and on Phrenic Nerve Activity in a Decerebrate Dog Model , 2001, Anesthesiology.

[23]  Z. Bosnjak,et al.  Differential Modulation of the Cardiac L- and T-type Calcium Channel Currents by Isoflurane , 2001, Anesthesiology.

[24]  J. Kendig,et al.  Enflurane Actions on Spinal Cords from Mice That Lack the &bgr;3 Subunit of the GABAA Receptor , 2001, Anesthesiology.

[25]  E. John,et al.  Invariant Reversible QEEG Effects of Anesthetics , 2001, Consciousness and Cognition.

[26]  C. Schwarzbauer,et al.  Subanesthetic Isoflurane Affects Task-induced Brain Activation in a Highly Specific Manner: A Functional Magnetic Resonance Imaging Study , 2001, Anesthesiology.

[27]  R. Cantor.  Breaking the Meyer-Overton rule: predicted effects of varying stiffness and interfacial activity on the intrinsic potency of anesthetics. , 2001, Biophysical journal.

[28]  H. Faulkner,et al.  Evidence for a Common Binding Cavity for Three General Anesthetics within the GABAA Receptor , 2001, The Journal of Neuroscience.

[29]  B. Orser,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 , 2001, Anesthesiology.

[30]  Astrid G. Stucke,et al.  Effects of Halothane on Excitatory Neurotransmission to Medullary Expiratory Neurons in a Decerebrate Dog Model , 2000, Anesthesiology.

[31]  J. Weinstein.  Pharmacogenomics--teaching old drugs new tricks. , 2000, The New England journal of medicine.

[32]  T. Yamakura,et al.  Effects of Gaseous Anesthetics Nitrous Oxide and Xenon on Ligand-gated Ion Channels: Comparison with Isoflurane and Ethanol , 2000, Anesthesiology.

[33]  J. Kendig,et al.  Enflurane Directly Depresses Glutamate AMPA and NMDA Currents in Mouse Spinal Cord Motor Neurons Independent of Actions on GABAA or Glycine Receptors , 2000, Anesthesiology.

[34]  J. B. Cohen,et al.  Identification of Sites of Incorporation in the Nicotinic Acetylcholine Receptor of a Photoactivatible General Anesthetic* , 2000, The Journal of Biological Chemistry.

[35]  J. Drummond,et al.  Monitoring depth of anesthesia: with emphasis on the application of the bispectral index and the middle latency auditory evoked response to the prevention of recall. , 2000, Anesthesiology.

[36]  J. H. Fallon,et al.  Toward a Unified Theory of Narcosis: Brain Imaging Evidence for a Thalamocortical Switch as the Neurophysiologic Basis of Anesthetic-Induced Unconsciousness , 2000, Consciousness and Cognition.

[37]  E. Eger,et al.  Naturally occurring variability in anesthetic potency among inbred mouse strains. , 2000, Anesthesia and analgesia.

[38]  D. Bayliss,et al.  The TASK-1 Two-Pore Domain K+ Channel Is a Molecular Substrate for Neuronal Effects of Inhalation Anesthetics , 2000, The Journal of Neuroscience.

[39]  J P Changeux,et al.  Nicotinic receptor function: new perspectives from knockout mice. , 2000, Trends in pharmacological sciences.

[40]  Z. Bosnjak,et al.  Modulation of cardiac inward rectifier K(+)current by halothane and isoflurane. , 2000, Anesthesia and analgesia.

[41]  J. Antognini,et al.  Isoflurane Action in the Spinal Cord Blunts Electroencephalographic and Thalamic–Reticular Formation Responses to Noxious Stimulation in Goats , 2000, Anesthesiology.

[42]  M. Lazdunski,et al.  Inhalational anesthetics activate two-pore-domain background K+ channels , 1999, Nature Neuroscience.

[43]  C. Yost,et al.  Potassium channels: basic aspects, functional roles, and medical significance. , 1999, Anesthesiology.

[44]  M. Nonet,et al.  A neomorphic syntaxin mutation blocks volatile-anesthetic action in Caenorhabditis elegans. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[45]  S. Roth,et al.  The effects of general anesthetics on excitatory and inhibitory synaptic transmission in area CA1 of the rat hippocampus in vitro. , 1999, Anesthesia and analgesia.

[46]  W. Shen,et al.  Effect of Nitrous Oxide on Excitatory and Inhibitory Synaptic Transmission in Hippocampal Cultures , 1998, The Journal of Neuroscience.

[47]  R. Dickinson,et al.  How does xenon produce anaesthesia? , 1998, Nature.

[48]  M. Halsey,et al.  Molecular similarity analysis: an alternative approach to studying molecular mechanisms of anaesthesia. , 1998, Toxicology letters.

[49]  P. Morgan,et al.  Control of anesthetic response in C. elegans. , 1998, Toxicology letters.

[50]  J. Lindstrom,et al.  Ion channel modulation as the basis for general anesthesia. , 1998, Toxicology letters.

[51]  S. Daniels,et al.  Post-synaptic inhibitory mechanisms of anaesthesia; glycine receptors. , 1998, Toxicology letters.

[52]  W. R. Lieb,et al.  Which molecular targets are most relevant to general anaesthesia? , 1998, Toxicology letters.

[53]  P. Flood,et al.  Neuronal nicotinic acetylcholine receptor modulation by general anesthetics. , 1998, Toxicology letters.

[54]  Yoshiharu Tanaka,et al.  Molecular genetical analysis of Drosophila ether sensitive mutants. , 1998, Toxicology letters.

[55]  R. Olsen,et al.  The molecular mechanism of action of general anesthetics: structural aspects of interactions with GABAA receptors , 1998 .

[56]  P. Brick,et al.  Structural basis for the inhibition of firefly luciferase by a general anesthetic. , 1998, Biophysical journal.

[57]  J. Stocks,et al.  A Comparison of the Respiratory Effects of Sevoflurane and Halothane in Infants and Young Children , 1998, Anesthesiology.

[58]  R. Twersky.  Ambulatory surgery update , 1998, Canadian journal of anaesthesia = Journal canadien d'anesthesie.

[59]  L. Firestone,et al.  Anesthesia Sensitivity in Mice that Lack the beta 3 Subunit of the gamma‐Aminobutyric Acid Type A Receptor , 1998, Anesthesiology.

[60]  L. H. Turner,et al.  Effects of desflurane, sevoflurane and halothane on postinfarction spontaneous dysrhythmias in dogs , 1998, Acta anaesthesiologica Scandinavica.

[61]  L. Firestone,et al.  Anesthesia Sensitivity in Mice that Lack the β3 Subunit of the γ-Aminobutyric Acid Type A Receptor , 1998 .

[62]  R. Dingledine,et al.  Differential Dependence on GluR2 Expression of Three Characteristic Features of AMPA Receptors , 1997, The Journal of Neuroscience.

[63]  Wiklund Ra,et al.  First of two parts , 1997 .

[64]  R. Harris,et al.  Sites of alcohol and volatile anaesthetic action on GABAA and glycine receptors , 1997, Nature.

[65]  M. Ghoneim,et al.  Learning and Memory during General Anesthesia: An Update , 1997, Anesthesiology.

[66]  R. Harris,et al.  Ethanol, flunitrazepam, and pentobarbital modulation of GABAA receptors expressed in mammalian cells and Xenopus oocytes. , 1997, Alcoholism, clinical and experimental research.

[67]  Murray H. Brilliant,et al.  Mice devoid of γ-aminobutyrate type A receptor β3 subunit have epilepsy, cleft palate, and hypersensitive behavior , 1997 .

[68]  A. Pohorille,et al.  Hypothesis: Inhaled Anesthetics Produce Immobility and Amnesia by Different Mechanisms at Different Sites , 1997, Anesthesia and analgesia.

[69]  W. R. Lieb,et al.  Differential Sensitivities of Mammalian Neuronal and Muscle Nicotinic Acetylcholine Receptors to General Anesthetics , 1997, Anesthesiology.

[70]  Yan Xu,et al.  Different distribution of fluorinated anesthetics and nonanesthetics in model membrane: a 19F NMR study. , 1997, Biophysical journal.

[71]  P. Flood,et al.  Alpha4beta2 Neuronal Nicotinic Acetylcholine Receptors in the Central Nervous System Are Inhibited by Isoflurane and Propofol, but alpha7‐type Nicotinic Acetylcholine Receptors Are Unaffected , 1997, Anesthesiology.

[72]  L. Firestone,et al.  Gene Knockout of the α6 Subunit of the γ-Aminobutyric Acid Type A Receptor: Lack of Effect on Responses to Ethanol, Pentobarbital, and General Anesthetics , 1997 .

[73]  D. Cafiso,et al.  Contrasting membrane localization and behavior of halogenated cyclobutanes that follow or violate the Meyer-Overton hypothesis of general anesthetic potency. , 1997, Biophysical journal.

[74]  Michael V. Cohen,et al.  Volatile Anesthetics Protect the Ischemic Rabbit Myocardium from Infarction , 1997, Anesthesiology.

[75]  R. Harris,et al.  Enhancement of homomeric glycine receptor function by longchain alcohols and anaesthetics , 1996, British journal of pharmacology.

[76]  B. Rehberg,et al.  Central Nervous System Sodium Channels Are Significantly Suppressed at Clinical Concentrations of Volatile Anesthetics , 1996, Anesthesiology.

[77]  R. Traub,et al.  Neuronal networks for induced ‘40 Hz’ rhythms , 1996, Trends in Neurosciences.

[78]  R. Lydic,et al.  Pontine Cholinergic Mechanisms Modulate the Cortical Electroencephalographic Spindles of Halothane Anesthesia , 1996, Anesthesiology.

[79]  A. Jenkins,et al.  Actions of general anaesthetics on 5‐HT3 receptors in N1E‐115 neuroblastoma cells , 1996, British journal of pharmacology.

[80]  A. Pohorille,et al.  Interactions of anesthetics with the membrane-water interface. , 1996, Chemical physics.

[81]  B. Chortkoff,et al.  Nonanesthetics Can Suppress Learning , 1996, Anesthesia and analgesia.

[82]  Peggy Mason,et al.  Anesthetic actions within the spinal cord: contributions to the state of general anesthesia , 1995, Trends in Neurosciences.

[83]  K. Miller,et al.  A discrete site for general anesthetics on a postsynaptic receptor. , 1995, Molecular pharmacology.

[84]  Y. Yaari,et al.  Effects of Halothane on Glutamate Receptor-mediated Excitatory Postsynaptic Currents: A Patch-Clamp Study in Adult Mouse Hippocampal Slices , 1995, Anesthesiology.

[85]  J. Hirsch,et al.  Costs incurred by outpatient surgical centers in managing postoperative nausea and vomiting. , 1995, Journal of clinical anesthesia.

[86]  N. Harrison,et al.  The effects of four general anesthetics on intracellular [Ca2+] in cultured rat hippocampal neurons , 1995, Neuropharmacology.

[87]  E. Eger,et al.  Polyhalogenated and perfluorinated compounds that disobey the Meyer-Overton hypothesis. , 1994, Anesthesia and analgesia.

[88]  E. Eger,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. , 1994, Molecular pharmacology.

[89]  N. Harrison,et al.  Potentiation of gamma-aminobutyric acidA receptor Cl- current correlates with in vivo anesthetic potency. , 1994, The Journal of pharmacology and experimental therapeutics.

[90]  C. Hemmings,et al.  Halothane And Propofol Increase Cofactor Sensitivity Of Purified Brain Protein Kinase , 1994 .

[91]  J. Hirsch,et al.  Costs incurred by outpatient surgical centers in managing postoperative nausea and vomiting , 1994 .

[92]  C. Lynch,et al.  Anesthetic alteration of ryanodine binding by cardiac calcium release channels. , 1994, Biochimica et biophysica acta.

[93]  J. Dilger,et al.  Evidence for Direct Actions of General Anesthetics on an Ion Channel Protein: A New Look at a Unified Mechanism of Action , 1994, Anesthesiology.

[94]  H. Hemmings,et al.  Effects of Halothane and Propofol on Purified Brain Protein Kinase C Activation , 1994, Anesthesiology.

[95]  H. Nash,et al.  Use of Drosophila mutants to distinguish among volatile general anesthetics. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[96]  W. R. Lieb,et al.  Molecular and cellular mechanisms of general anaesthesia , 1994, Nature.

[97]  J. Antognini,et al.  Exaggerated Anesthetic Requirements in the Preferentially Anesthetized Brain , 1993, Anesthesiology.

[98]  N L Harrison,et al.  Effects of volatile anesthetics on the kinetics of inhibitory postsynaptic currents in cultured rat hippocampal neurons. , 1993, Journal of neurophysiology.

[99]  N. Harrison,et al.  Positive modulation of human gamma-aminobutyric acid type A and glycine receptors by the inhalation anesthetic isoflurane. , 1993, Molecular pharmacology.

[100]  A. Angel,et al.  Central neuronal pathways and the process of anaesthesia. , 1993, British journal of anaesthesia.

[101]  S. Slater,et al.  Inhibition of protein kinase C by alcohols and anaesthetics , 1993, Nature.

[102]  D. Raines,et al.  Anesthetic Cutoff in Cycloalkanemethanols: A Test of Current Theories , 1993, Anesthesiology.

[103]  Longtang L. Chen,et al.  Enflurane inhibits NMDA, AMPA, and kainate‐induced currents in Xenopus oocytes expressing mouse and human brain mRNA , 1993, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[104]  B. Sakmann,et al.  Determinants of ca2+ permeability in both TM1 and TM2 of high affinity kainate receptor channels: Diversity by RNA editing , 1993, Neuron.

[105]  E. Eger,et al.  Effects of isoflurane and nitrous oxide in subanesthetic concentrations on memory and responsiveness in volunteers. , 1992, Anesthesiology.

[106]  C. Lynch,et al.  Halothane and isoflurane effects on Ca2+ fluxes of isolated myocardial sarcoplasmic reticulum. , 1992, Anesthesiology.

[107]  E. Eger,et al.  Isoflurane Anesthesia Prevents Unconscious Learning , 1992, Anesthesia and analgesia.

[108]  W. R. Lieb,et al.  Role of hydrogen bonding in general anesthesia. , 1991, Journal of pharmaceutical sciences.

[109]  J. Kendig,et al.  Anesthetic Actions in the Hippocampal Formation , 1991, Annals of the New York Academy of Sciences.

[110]  Z. Bosnjak,et al.  Differential effects of halothane, enflurane, and isoflurane on Ca2+ transients and papillary muscle tension in guinea pigs. , 1988, Anesthesiology.

[111]  K. Miller,et al.  Barbiturates bind to an allosteric regulatory site on nicotinic acetylcholine receptor-rich membranes. , 1987, Molecular pharmacology.

[112]  W. R. Lieb,et al.  Mapping of general anaesthetic target sites provides a molecular basis for cutoff effects , 1985, Nature.

[113]  N. P. Franks,et al.  Do general anaesthetics act by competitive binding to specific receptors? , 1984, Nature.

[114]  N. P. Franks,et al.  Molecular mechanisms of general anaesthesia , 1982, Nature.

[115]  M F Roizen,et al.  Anesthetic Doses Blocking Adrenergic (Stress) and Cardiovascular Responses to Incision—MAC BAR , 1981, Anesthesiology.

[116]  E. Eger,et al.  Selective Breeding Alters Murine Resistance to Nitrous Oxide Without Alteration in Synaptic Membrane Lipid Composition , 1980, Anesthesiology.

[117]  N. P. Franks,et al.  Where do general anaesthetics act? , 1978, Nature.

[118]  E. B. Smith,et al.  General anaesthetics and bacterial luminescence I. The effect of diethyl ether on the in vivo light emission of Vibrio fischeri , 1976, Proceedings of the Royal Society of London. Series B. Biological Sciences.

[119]  R. T. Pivik,et al.  Selective firing by cat pontine brain stem neurons in desynchronized sleep. , 1974, Journal of neurophysiology.

[120]  C. Leake.  Claude Bernard and anesthesia. , 1971, Anesthesiology.

[121]  E. Eger,et al.  Minimum Alveolar Concentrations in Man on Awakening from Methoxyflurane, Halothane, Ether and Fluroxene Anesthesia: MAC Awake , 1970, Anesthesiology.

[122]  P. Mann,et al.  Reticular and thalamic multiple unit activity during wakefulness, sleep and anesthesia. , 1967, Experimental neurology.

[123]  E. Eger,et al.  Minimum alveolar anesthetic concentration: a standard of anesthetic potency. , 1965, Anesthesiology.

[124]  F. W. Clement.  SURGERY BEFORE THE DAYS OF ANESTHESIA , 1953, Anesthesiology.

[125]  H. Meyer.  Zur Theorie der Alkoholnarkose , 1899, Archiv für experimentelle Pathologie und Pharmakologie.

[126]  P. Maurette,et al.  [To err is human: building a safer health system]. , 2002, Annales francaises d'anesthesie et de reanimation.

[127]  J. Fritschy,et al.  A new benzodiazepine pharmacology. , 2002, The Journal of pharmacology and experimental therapeutics.

[128]  W. Hevers,et al.  Altered receptor subtypes in the forebrain of GABA(A) receptor delta subunit-deficient mice: recruitment of gamma 2 subunits. , 2002, Neuroscience.

[129]  W. Evans,et al.  Pharmacogenomics: unlocking the human genome for better drug therapy. , 2001, Annual review of pharmacology and toxicology.

[130]  B. Antkowiak,et al.  [Neural mechanisms of anesthesia]. , 2000, Anasthesiologie, Intensivmedizin, Notfallmedizin, Schmerztherapie : AINS.

[131]  L. Firestone,et al.  Gene knockout of the alpha6 subunit of the gamma-aminobutyric acid type A receptor: lack of effect on responses to ethanol, pentobarbital, and general anesthetics. , 1997, Molecular pharmacology.

[132]  M. Brilliant,et al.  Mice devoid of gamma-aminobutyrate type A receptor beta3 subunit have epilepsy, cleft palate, and hypersensitive behavior. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[133]  P. Tonner,et al.  Channel inhibition by alkanols occurs at a binding site on the nicotinic acetylcholine receptor. , 1995, Molecular pharmacology.

[134]  R. Olsen,et al.  GABAA receptor channels. , 1994, Annual review of neuroscience.

[135]  J. Kendig,et al.  Anesthetic effects on resting membrane potential are voltage-dependent and agent-specific. , 1991, Anesthesiology.

[136]  C. D. Richards,et al.  Cellular mechanisms in general anaesthesia. , 1991, British journal of anaesthesia.

[137]  K. Miller,et al.  The nature of the site of general anesthesia. , 1985, International review of neurobiology.

[138]  D. Koblin,et al.  Anaesthetic requirement in mice selectively bred for differences in ethanol sensitivity. , 1981, British journal of anaesthesia.

[139]  E. Overton.  Studien über die Narkose : zugleich ein Beitrag zur allgemeinen Pharmakologie , 1901 .