General anaesthesia: from molecular targets to neuronal pathways of sleep and arousal

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Sites of alcohol and volatile anaesthetic action on GABAA and glycine receptors

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The neural circuit of orexin (hypocretin): maintaining sleep and wakefulness

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Molecular and neuronal substrates for general anaesthetics

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Do general anaesthetics act by competitive binding to specific receptors?

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The sedative component of anesthesia is mediated by GABAA receptors in an endogenous sleep pathway

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Binding of the General Anesthetics Propofol and Halothane to Human Serum Albumin

2000 • 512 citations

Functional neuroimaging of normal human sleep by positron emission tomography

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TREK-1, a K+ channel involved in neuroprotection and general anesthesia

2004 • 505 citations

Identification of sleep-promoting neurons in vitro

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Sleep–waking discharge patterns of ventrolateral preoptic/anterior hypothalamic neurons in rats

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Molecular mechanisms of general anaesthesia

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Effects of locus coeruleus activation on electroencephalographic activity in neocortex and hippocampus

1991 • 417 citations

A Hypnotic Response to Dexmedetomidine, an α2 Agonist, Is Mediated in the Locus Coerüleus in Rats

1992 • 393 citations

Toward a Unified Theory of Narcosis: Brain Imaging Evidence for a Thalamocortical Switch as the Neurophysiologic Basis of Anesthetic-Induced Unconsciousness

2000 • 390 citations

Thalamic synchrony and dynamic regulation of global forebrain oscillations

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The interaction of the general anesthetic etomidate with the γ-aminobutyric acid type A receptor is influenced by a single amino acid

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Organization of histaminergic fibers in the rat brain

1988 • 370 citations

Distinct Functional and Pharmacological Properties of Tonic and Quantal Inhibitory Postsynaptic Currents Mediated by γ-Aminobutyric Acid_A Receptors in Hippocampal Neurons

2001 • 363 citations

Neuroanatomical correlates of brainstem coma

2003 • 360 citations

Effects of Gaseous Anesthetics Nitrous Oxide and Xenon on Ligand-gated Ion Channels

2000 • 359 citations

Neuronal Activity of Histaminergic Tuberomammillary Neurons During Wake–Sleep States in the Mouse

2006 • 357 citations

Regional Cerebral Blood Flow Changes as a Function of Delta and Spindle Activity during Slow Wave Sleep in Humans

1997 • 356 citations

The Interaction of Fentanyl on the Cp50 of Propofol for Loss of Consciousness and Skin Incision

1994 • 322 citations

Inhaled Anesthetics and Immobility: Mechanisms, Mysteries, and Minimum Alveolar Anesthetic Concentration

2003 • 322 citations

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1995 • 320 citations

General Anesthetics Hyperpolarize Neurons in the Vertebrate Central Nervous System

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The adrenergic innervation of the rat thalamus as revealed by the glyoxylic acid fluorescence method

1974 • 312 citations

An essential role for orexins in emergence from general anesthesia

2008 • 310 citations

Brainstem projections to midline and intralaminar thalamic nuclei of the rat

2002 • 309 citations

Neurophysiologic Effects of General Anesthetics

1973 • 309 citations

Projections of cholinergic and non-cholinergic neurons of the brainstem core to relay and associational thalamic nuclei in the cat and macaque monkey

1988 • 305 citations

GABA _A receptor α4 subunits mediate extrasynaptic inhibition in thalamus and dentate gyrus and the action of gaboxadol

2006 • 305 citations

Two-Pore-Domain K⁺ Channels Are a Novel Target for the Anesthetic Gases Xenon, Nitrous Oxide, and Cyclopropane

2004 • 297 citations

The Interaction of Fentanyl on the Cp50 of Propofol for Loss of Consciousness and Skin Incision

1994 • 294 citations

Cholinergic projections from the midbrain and pons to the thalamus in the rat, identified by combined retrograde tracing and choline acetyltransferase immunohistochemistry

1985 • 293 citations

Serotonin and sleep

2002 • 291 citations

Sedation and anesthesia mediated by distinct GABA(A) receptor isoforms.

2003 • 290 citations

Projections of brainstem core cholinergic and non-cholinergic neurons of cat to intralaminar and reticular thalamic nuclei

1988 • 289 citations

Stereospecific Effects of Inhalational General Anesthetic Optical Isomers on Nerve Ion Channels

1991 • 284 citations

Identification of a GABA_AReceptor Anesthetic Binding Site at Subunit Interfaces by Photolabeling with an Etomidate Analog

2006 • 284 citations

Brainstem afferents to the magnocellular basal forebrain studied by axonal transport, immunohistochemistry, and electrophysiology in the rat

1988 • 275 citations

Magnocellular Nuclei of the Basal Forebrain: Substrates of Sleep and Arousal Regulation

1995 • 272 citations

A Single Glycine Residue at the Entrance to the First Membrane-Spanning Domain of the γ-Aminobutyric Acid Type A Receptor β₂Subunit Affects Allosteric Sensitivity to GABA and Anesthetics

2000 • 271 citations

Specific binding sites for alcohols and anesthetics on ligand-gated ion channels

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Quantitative EEG changes associated with loss and return of consciousness in healthy adult volunteers anaesthetized with propofol or sevoflurane

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Sleep-related neuronal discharge in the basal forebrain of cats

1986 • 264 citations

Propofol and Other Intravenous Anesthetics Have Sites of Action on the γ-Aminobutyric Acid Type A Receptor Distinct from That for Isoflurane

1998 • 253 citations

Anesthetic Effects on Electrophysiologic Recordings

1998 • 252 citations

The TASK-1 Two-Pore Domain K⁺ Channel Is a Molecular Substrate for Neuronal Effects of Inhalation Anesthetics

2000 • 251 citations

Sedation and Anesthesia Mediated by Distinct GABA_AReceptor Isoforms

2003 • 247 citations

Extrasynaptic GABA_AReceptors of Thalamocortical Neurons: A Molecular Target for Hypnotics

2005 • 247 citations

Evidence for a Common Binding Cavity for Three General Anesthetics within the GABA_AReceptor

2001 • 240 citations

Contrasting Synaptic Actions of the Inhalational General Anesthetics Isoflurane and Xenon

2000 • 240 citations

An Extrasynaptic GABA_A Receptor Mediates Tonic Inhibition in Thalamic VB Neurons

2005 • 238 citations

Mapping of general anaesthetic target sites provides a molecular basis for cutoff effects

1985 • 236 citations

α5GABA_AReceptors Mediate the Amnestic But Not Sedative-Hypnotic Effects of the General Anesthetic Etomidate

2006 • 235 citations

A Unitary Theory of Anesthesia Based on Lateral Phase Separations in Nerve Membranes

1977 • 235 citations

Sleep, Anesthesiology, and the Neurobiology of Arousal State Control

2005 • 234 citations

Subunit‐dependent interaction of the general anaesthetic etomidate with the γ‐aminobutyric acid type A receptor

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Barbiturate receptor sites are coupled to benzodiazepine receptors.

1980 • 234 citations

Subregional organization of preoptic area /anterior hypothalamic projections to arousal-related monoaminergic cell groups

2000 • 231 citations

Competitive Inhibition at the Glycine Site of the N -Methyl-d-aspartate Receptor by the Anesthetics Xenon and Isoflurane

2007 • 231 citations

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 • 228 citations

Impaired thalamocortical connectivity in humans during general-anesthetic-induced unconsciousness

2003 • 225 citations

Thalamic Microinjection of Nicotine Reverses Sevoflurane-induced Loss of Righting Reflex in the Rat

2007 • 224 citations

The pressure reversal of general anesthesia and the critical volume hypothesis.

1973 • 223 citations

Differential Sensitivities of Mammalian Neuronal and Muscle Nicotinic Acetylcholine Receptors to General Anesthetics

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Feedback inhibition controls spike transfer in hybrid thalamic circuits

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Differential Dynamic of Action on Cortical and Subcortical Structures of Anesthetic Agents during Induction of Anesthesia

2007 • 207 citations

Enhancement of homomeric glycine receptor function by longchain alcohols and anaesthetics

1996 • 201 citations

The General Anesthetic Propofol Slows Deactivation and Desensitization of GABA_AReceptors

1999 • 201 citations

An intracellular proton sensor commands lipid- and mechano-gating of the K+ channel TREK-1

2002 • 201 citations

Volatile general anaesthetics activate a novel neuronal K+ current

1988 • 199 citations

Motoneurons Express Heteromeric TWIK-Related Acid-Sensitive K⁺(TASK) Channels Containing TASK-1 (KCNK3) and TASK-3 (KCNK9) Subunits

2004 • 199 citations

Temperature Dependence of the Potency of Volatile General Anesthetics

1996 • 198 citations

Sleep‐waking discharge patterns of median preoptic nucleus neurons in rats

2002 • 197 citations

Effects of Xenon on In Vitro and In Vivo Models of Neuronal Injury

2002 • 189 citations

Modulation of TASK-1 (Kcnk3) and TASK-3 (Kcnk9) Potassium Channels

2002 • 183 citations

Activity of Midbrain Reticular Formation and Neocortex during the Progression of Human Non-Rapid Eye Movement Sleep

1999 • 178 citations

Physostigmine Reverses Propofol-induced Unconsciousness and Attenuation of the Auditory Steady State Response and Bispectral Index in Human Volunteers

2000 • 175 citations

Different Actions of Anticonvulsant and Anesthetic Barbiturates Revealed by Use of Cultured Mammalian Neurons

1978 • 175 citations

Neocortex is the major target of sedative concentrations of volatile anaesthetics: strong depression of firing rates and increase of GABA_A receptor‐mediated inhibition

2005 • 172 citations

Defining the Propofol Binding Site Location on the GABA_A Receptor

2004 • 171 citations

Reversible analgesia, atonia, and loss of consciousness on bilateral intracerebral microinjection of pentobarbital

2001 • 170 citations

Contribution of TWIK-Related Acid-Sensitive K⁺Channel 1 (TASK1) and TASK3 Channels to the Control of Activity Modes in Thalamocortical Neurons

2003 • 165 citations

Positive modulation of human gamma-aminobutyric acid type A and glycine receptors by the inhalation anesthetic isoflurane.

1993 • 164 citations

Stereoselective Effects of Etomidate Optical Isomers on Gamma-aminobutyric Acid Type A Receptors and Animals

1998 • 162 citations

S -Ketamine Anesthesia Increases Cerebral Blood Flow in Excess of the Metabolic Needs in Humans

2005 • 162 citations

Modification of neocortical acetylcholine release and electroencephalogram desynchronization due to brainstem stimulation by drugs applied to the basal forebrain

1994 • 158 citations

Mechanism of Anesthesia Revealed by Shunting Actions of Isoflurane on Thalamocortical Neurons

1999 • 156 citations

Serotonergic Raphe Neurons Express TASK Channel Transcripts and a TASK-Like pH- and Halothane-Sensitive K⁺Conductance

2002 • 155 citations

Partitioning of long-chain alcohols into lipid bilayers: implications for mechanisms of general anesthesia.

1986 • 154 citations

Selective Enhancement of Tonic GABAergic Inhibition in Murine Hippocampal Neurons by Low Concentrations of the Volatile Anesthetic Isoflurane

2004 • 149 citations

Sleep-waking discharge of basal forebrain projection neurons in cats

1989 • 146 citations

Selective Action of Orexin (Hypocretin) on Nonspecific Thalamocortical Projection Neurons

2002 • 143 citations

Modulation of NMDA Receptor Function by Ketamine and Magnesium. Part II: Interactions with Volatile Anesthetics

2001 • 141 citations

The actions of ether, alcohol and alkane general anaesthetics on GABA_A and glycine receptors and the effects of TM2 and TM3 mutations

2000 • 140 citations

Molecular determinants for the action of general anesthetics at recombinant α₂β₃γ₂γ‐aminobutyric acid_A receptors

2001 • 136 citations

Looking back: corticothalamic feedback and early visual processing

2006 • 133 citations

Methionine 286 in transmembrane domain 3 of the GABAA receptor β subunit controls a binding cavity for propofol and other alkylphenol general anesthetics

2001 • 129 citations

Effects of inhalational general anaesthetics on native glycine receptors in rat medullary neurones and recombinant glycine receptors in Xenopus oocytes

1996 • 128 citations

The Septohippocampal System Participates in General Anesthesia

2002 • 127 citations

Propofol Anesthesia and Cerebral Blood Flow Changes Elicited by Vibrotactile Stimulation: A Positron Emission Tomography Study

2001 • 127 citations

Major Role For Tonic GABA_A Conductances in Anesthetic Suppression of Intrinsic Neuronal Excitability

2004 • 126 citations

Influence of Age on Hypnotic Requirement, Bispectral Index, and 95% Spectral Edge Frequency Associated with Sedation Induced by Sevoflurane

2000 • 123 citations

Neuronal activity in the peribrachial area: Relationship to behavioral state control

1995 • 120 citations

Wake-Promoting Actions of Dopamine D1 and D2 Receptor Stimulation

2003 • 119 citations

Ethanol Inhibition ofN-Methyl-d-aspartate Receptors Is Reduced by Site-directed Mutagenesis of a Transmembrane Domain Phenylalanine Residue

2001 • 119 citations

Structural basis for high‐affinity volatile anesthetic binding in a natural 4‐helix bundle protein

2005 • 118 citations

Efferent projections from the median preoptic nucleus to sleep- and arousal-regulatory nuclei in the rat brain

2007 • 117 citations

Innervation of orexin/hypocretin neurons by GABAergic, glutamatergic or cholinergic basal forebrain terminals evidenced by immunostaining for presynaptic vesicular transporter and postsynaptic scaffolding proteins

2006 • 116 citations

Brain structures and mechanisms involved in the generation of NREM sleep: focus on the preoptic hypothalamus

2001 • 114 citations

Gating Allosterism at a Single Class of Etomidate Sites on α1β2γ2L GABAA Receptors Accounts for Both Direct Activation and Agonist Modulation

2004 • 111 citations

Stereoselective and non‐stereoselective actions of isoflurane on the GABA_A receptor

1994 • 111 citations

Isoflurane and Propofol Inhibit Voltage-Gated Sodium Channels in Isolated Rat Neurohypophysial Nerve Terminals

2003 • 107 citations

Sleep Deprivation Potentiates the Onset and Duration of Loss of Righting Reflex Induced by Propofol and Isoflurane

2002 • 106 citations

Gabaergic neurons with α2-adrenergic receptors in basal forebrain and preoptic area express c-Fos during sleep

2004 • 104 citations

Effects of Halothane on Glutamate Receptor-mediated Excitatory Postsynaptic Currents

1995 • 104 citations

Potent Activation of the Human Tandem Pore Domain K Channel TRESK with Clinical Concentrations of Volatile Anesthetics

2004 • 102 citations

Wake-related activity of tuberomammillary neurons in rats

2003 • 101 citations

Monitoring consciousness: the current status of EEG-based depth of anaesthesia monitors

2007 • 101 citations

Convergent and reciprocal modulation of a leak K⁺ current and I_h by an inhalational anaesthetic and neurotransmitters in rat brainstem motoneurones

2002 • 93 citations

Orexinergic neurons and barbiturate anesthesia

2003 • 92 citations

Extracellular histamine levels in the feline preoptic/anterior hypothalamic area during natural sleep–wakefulness and prolonged wakefulness: An in vivo microdialysis study

2002 • 92 citations

Effects of Anesthetics on Mutant N-Methyl-d-Aspartate Receptors Expressed in Xenopus Oocytes

2006 • 92 citations

Differential Modulation of Human N-Methyl-d-Aspartate Receptors by Structurally Diverse General Anesthetics

2006 • 91 citations

Pentobarbital: Differential Postsynaptic Actions on Sympathetic Ganglion Cells

1978 • 89 citations

Isoflurane induces dose-dependent changes of thalamic somatosensory information transfer

1999 • 89 citations

Propofol block of I_h contributes to the suppression of neuronal excitability and rhythmic burst firing in thalamocortical neurons

2006 • 87 citations

Role of Hydrogen Bonding in General Anesthesia

1991 • 86 citations

Protein Crystallography under Xenon and Nitrous Oxide Pressure: Comparison with In Vivo Pharmacology Studies and Implications for the Mechanism of Inhaled Anesthetic Action

2006 • 86 citations

The G. L. Brown lecture. Adventures in anaesthesia

1991 • 86 citations

Agonist Gating and Isoflurane Potentiation in the Human γ-Aminobutyric Acid Type A Receptor Determined by the Volume of a Second Transmembrane Domain Residue

1999 • 85 citations

2-(3-Methyl-3H-diaziren-3-yl)ethyl 1-(1-phenylethyl)-1H-imidazole-5-carboxylate: A Derivative of the Stereoselective General Anesthetic Etomidate for Photolabeling Ligand-Gated Ion Channels

2003 • 85 citations

Pontine Cholinergic Mechanisms Modulate the Cortical Electroencephalographic Spindles of Halothane Anesthesia

1996 • 84 citations

HCN Subunit-Specific and cAMP-Modulated Effects of Anesthetics on Neuronal Pacemaker Currents

2005 • 84 citations

The in Vivo Contributions of TASK-1-Containing Channels to the Actions of Inhalation Anesthetics, the α₂ Adrenergic Sedative Dexmedetomidine, and Cannabinoid Agonists

2006 • 83 citations

Volatile anesthetic actions on the GABAA receptors: contrasting effects of α1(S270) and β2(N265) point mutations

2002 • 80 citations

Anesthetic influences on the basal acticity and pharmacological responsiveness of nigrostriatal dopamine neurons

1990 • 80 citations

Distinct molecular targets for the central respiratory and cardiac actions of the general anesthetics etomidate and propofol

2005 • 79 citations

Photoaffinity Labeling with a Neuroactive Steroid Analogue

2003 • 76 citations

Neural pathways associated with loss of consciousness caused by intracerebral microinjection of GABA_A‐active anesthetics

2007 • 76 citations

HYPERCAPNIC ISCHEMIA IN A NEW ADULT RAT BRAIN SLICE PREPARATION FOR EX VIVO NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY STUDIES

1994 • 75 citations

Prolonged Sedation with Propofol in the Rat Does Not Result in Sleep Deprivation

2001 • 74 citations

Effects of Halothane on GABA_AReceptor Kinetics: Evidence for Slowed Agonist Unbinding

2000 • 74 citations

Identification of a Molecular Target Mediating the General Anesthetic Actions of Pentobarbital

2006 • 73 citations

Effect of Isoflurane and Other Potent Inhaled Anesthetics on Minimum Alveolar Concentration, Learning, and the Righting Reflex in Mice Engineered to Express α1γ-Aminobutyric Acid Type A Receptors Unresponsive to Isoflurane

2007 • 73 citations

Synaptic Mechanisms of Thiopental-induced Alterations in Synchronized Cortical Activity

1996 • 71 citations

Effects of Alcohols and Anesthetics on Recombinant Voltage-Gated Na⁺ Channels

2004 • 71 citations

Implication of dopaminergic mechanisms in the wake-promoting effects of amphetamine: a study of d- and l-derivatives in canine narcolepsy

2000 • 66 citations

Contrasting anesthetic sensitivities of T‐type Ca²⁺ channels of reticular thalamic neurons and recombinant Ca_v3.3 channels

2004 • 65 citations

Effects of Xenon Anesthesia on Cerebral Blood Flow in Humans

2007 • 63 citations

Cerebral hypnogenic centers

1977 • 61 citations

Stereoselective Loss of Righting Reflex in Rats by Isoflurane

2000 • 60 citations

Tryptophan scanning mutagenesis in TM4 of the GABAA receptor α1 subunit: implications for modulation by inhaled anesthetics and ion channel structure

2002 • 60 citations

Thermodynamics of anesthetic/protein interactions. Temperature studies on firefly luciferase

1993 • 58 citations

Nonhalogenated Alkane Anesthetics Fail to Potentiate Agonist Actions on Two Ligand-gated Ion Channels

2001 • 57 citations

A Single M1 Residue in the β2 Subunit Alters Channel Gating of GABAA Receptor in Anesthetic Modulation and Direct Activation

2003 • 55 citations

Isoform-selective Effects of Isoflurane on Voltage-gated Na+ Channels

2007 • 53 citations

Sites in the fourth membrane-associated domain regulate alcohol sensitivity of the NMDA receptor

2004 • 52 citations

Sleep-promoting functions of the hypothalamic median preoptic nucleus: inhibition of arousal systems.

2004 • 50 citations

The role of the NMDA synapse in general anesthesia

1998 • 49 citations

Effects of general anesthetics on the bacterial luciferase enzyme from Vibrio harveyi: an anesthetic target site with differential sensitivity

1990 • 48 citations

Halothane-induced hyperpolarization and depression of postsynaptic potentials of guinea pig thalamic neurons in vitro

1992 • 48 citations

A Conserved Tyrosine in the β2Subunit M4 Segment Is a Determinant of γ-Aminobutyric Acid Type A Receptor Sensitivity to Propofol

2007 • 47 citations

Determinants of the Anesthetic Sensitivity of Two-pore Domain Acid-sensitive Potassium Channels

2007 • 46 citations

The Common Chemical Motifs Within Anesthetic Binding Sites

2007 • 45 citations

Preparation of Barbiturate Optical Isomers and Their Effects on GABA (A) Receptors

1999 • 45 citations

Heteromeric Nicotinic Inhibition by Isoflurane Does Not Mediate MAC or Loss of Righting Reflex

2002 • 42 citations

Determinants of the Sensitivity of AMPA Receptors to Xenon

2004 • 41 citations

Antagonists of the NMDA receptor-channel complex and motor coordination

1995 • 37 citations

Interaction of Intravenous Anesthetics with Recombinant Human M1-M3 Muscarinic Receptors Expressed in Chinese Hamster Ovary Cells

2002 • 36 citations

γ-Aminobutyric Acid Type A Receptor β2 Subunit Mediates the Hypothermic Effect of Etomidate in Mice

2004 • 36 citations

What can in vivo electrophysiology in animal models tell us about mechanisms of anaesthesia?

2002 • 32 citations

Reduced inhibition of cortical glutamate and GABA release by halothane in mice lacking the K⁺ channel, TREK‐1

2007 • 32 citations

The hypnotic effect of propofol in the medial preoptic area of the rat

2001 • 31 citations

Sleep induction by microinjection of pentobarbital into the medial preoptic area in rats

1996 • 30 citations

Preoptic area warming inhibits wake-active neurons in the perifornical lateral hypothalamus

2003 • 28 citations

Evaluating the energetics of empty cavities and internal mutations in proteins

1997 • 27 citations

Halogenated Diazirines as Photolabel Mimics of the Inhaled Haloalkane Anesthetics

2002 • 23 citations

Interactions Between Neuronal Histamine and Halothane Anesthesia in Rats

1997 • 23 citations

Transmembrane residues define the action of isoflurane at the GABAA receptor alpha-3 subunit

2004 • 23 citations

The sensitivity of hyperpolarization-activated cation current (Ih) to propofol in rat area postrema neurons

2004 • 14 citations

Contradicting a Unitary Theory of General Anesthetic Action: a History of Three Compounds from 1901 to 2001

2003 • 13 citations

Xenon suppresses nociceptive reflex in newborn rat spinal cord in vitro; comparison with nitrous oxide

2004 • 13 citations

Reevaluation of ACEA 1021 as an antagonist at the strychnine-insensitive glycine site of the N-methyl-d-aspartate receptor

1998 • 11 citations

Deleted Work

1955 • 0 citations