Do general anaesthetics act by competitive binding to specific receptors?

Franks, N. P.; Lieb, W. R.

doi:10.1038/310599a0

Cited by 574Anesthesia and Sedative AgentsAnesthesia and Neurotoxicity ResearchNeuroscience and Neuropharmacology Research

Do general anaesthetics act by competitive binding to specific receptors?

Franks, N. P., Lieb, W. R.·1984·Nature

DOI 10.1038/310599a0

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Abstract

Most proteins are insensitive to the presence of anaesthetics at concentrations which induce general anaesthesia, while some are inhibited by certain agents but not others. Here we show that, over a 100,000-fold range of potencies, the activity of a pure soluble protein (firefly luciferase) can be inhibited by 50% at anaesthetic concentrations which are essentially identical to those which anaesthetize animals. This identity holds for inhalational agents (such as halothane, methoxyflurane and chloroform), aliphatic and aromatic alcohols, ketones, ethers and alkanes. This finding is all the more striking in view of the fact that the inhibition is shown to be competitive in nature, with anaesthetic molecules competing with substrate (luciferin) molecules for binding to the protein. We show that the anaesthetic-binding site can accommodate only one large, but more than one small, anaesthetic molecule. The obvious mechanism suggested by our results is that general anaesthetics, despite their chemical and structural diversity, act by competing with endogenous ligands for binding to specific receptors.

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Stereoselective optical isomers of anesthetics with identical lipid solubility but lower potency challenged the non-specific lipid theory of anesthetic action.
“together with the discovery of stereoselective optical isomers of anesthetics with identical lipid solubility but reduced potency, called into question the non-specific lipid theory of anesthetic action [32].”
From The Biology of General Anesthesia from Paramecium to Primate (2019) · cites this paper as [32]
Distinct anesthetic drugs inhibit firefly luciferase over a six-order-of-magnitude range in a cell-free system.
“Subsequent recognition that distinct anesthetic drugs could similarly inhibit the protein firefly luciferase over an identical six-order of magnitude range in a cell-free environment”
From The Biology of General Anesthesia from Paramecium to Primate (2019) · cites this paper as [32]

Fundamentals of Enzyme Kinetics
Cornish-Bowden, A. J. (1979) · Elsevier eBooks · doi:10.1016/c2013-0-04130-8 · Cited by 2,079 · see citing works
Molecular mechanisms of general anaesthesia
Franks, N. P., & Lieb, W. R. (1982) · Nature · doi:10.1038/300487a0 · Cited by 436 · see citing works
Self-citation
Fundamentals of Enzyme Kinetics
Gutfreund, H. (1980) · FEBS Letters · doi:10.1016/0014-5793(80)80546-1 · Cited by 387 · see citing works
Kinetics of the firefly luciferase catalyzed reactions
DeLuca, M. A., & McElroy, W. D. (1974) · Biochemistry · doi:10.1021/bi00702a015 · Cited by 258 · see citing works
Where do general anaesthetics act?
Franks, N. P., & Lieb, W. R. (1978) · Nature · doi:10.1038/274339a0 · Cited by 256 · see citing works
Self-citation
SOLUBILITY COEFFICIENTS FOR INHALED ANAESTHETICS FOR WATER, OIL AND BIOLOGICAL MEDIA
Steward, A. N., ALLOTT, P. R., Cowles, A. L., & MAPLESON, W. W. (1973) · British Journal of Anaesthesia · doi:10.1093/bja/45.3.282 · Cited by 242 · see citing works
Free energies, enthalpies, and entropies of solution of gaseous nonpolar nonelectrolytes in water and nonaqueous solvents. The hydrophobic effect
Abraham, M. H. (1982) · Journal of the American Chemical Society · doi:10.1021/ja00372a001 · Cited by 209 · see citing works
Degenerate perturbations of protein structure as the mechanism of anaesthetic action
Richards, C. D., Martin, K. J., Gregory, S., Keightley, C. A., Hesketh, T. R., Smith, G. A., Warren, G., & Metcalfe, J. C. (1978) · Nature · doi:10.1038/276775a0 · Cited by 191 · see citing works
Hydrophobic nature of the active site of firefly luciferase
DeLuca, M. (1969) · Biochemistry · doi:10.1021/bi00829a023 · Cited by 134 · see citing works
Thermodynamic analysis of the relative effectiveness of narcotics
Brink, F., & Posternak, J. M. (1948) · Journal of Cellular and Comparative Physiology · doi:10.1002/jcp.1030320208 · Cited by 132 · see citing works
Substrate-binding properties of firefly luciferase
Denburg, J. L., Lee, R. T., & McElroy, W. D. (1969) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(69)90297-5 · Cited by 117 · see citing works
Hydrophobic Interactions in Proteins. The Alkane Binding Site of β-Lactoglobulins A and B*
Wishnia, A., & Pinder, T. (1966) · Biochemistry · doi:10.1021/bi00869a013 · Cited by 109 · see citing works
Kinetic and Thermodynamic Aspects of the Mechanism of General Anesthesia in a Model System of Firefly Luminescence in Vitro
Ueda, I., & Kamaya, H. (1973) · Anesthesiology · doi:10.1097/00000542-197305000-00002 · Cited by 100 · see citing works
Temperature Dependence of Anesthesia in Goldfish
Cherkin, A., & Catchpool, J. F. (1964) · Science · doi:10.1126/science.144.3625.1460 · Cited by 78 · see citing works
The partial molar volumes of anesthetics in lipid bilayers
Kita, Y. A., Bennett, L. J., & Miller, K. W. (1981) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/0005-2736(81)90301-1 · Cited by 54 · see citing works
Effect of Anaesthetics on Emission of Light by Luminous Bacteria
White, D., & Dundas, C. (1970) · Nature · doi:10.1038/226456a0 · Cited by 51 · see citing works
Aromatic hydrophobes and β-lactoglobulin A. Thermodynamics of binding
Robillard, K. A., & Wishnia, A. (1972) · Biochemistry · doi:10.1021/bi00771a001 · Cited by 44 · see citing works
Effects of Anaesthetics on Luminous Bacteria
Halsey, M. J., & Smith, E. B. (1970) · Nature · doi:10.1038/2271363b0 · Cited by 41 · see citing works
A guide to molecular pharmacology-toxicology
Orrenius, S., & Grundin, R. (1974) · Forensic Science · doi:10.1016/0300-9432(74)90089-2 · Cited by 40 · see citing works
A guide to molecular pharmacology-toxicology,
Featherstone, R. M. (1973) · Medical Entomology and Zoology · Cited by 32 · see citing works
A convenient affinity chromatography-based purification of firefly luciferase
Branchini, B. R., Marschner, T. M., & Montemurro, A. M. (1980) · Analytical Biochemistry · doi:10.1016/0003-2697(80)90089-5 · Cited by 28 · see citing works
Mechanism of inhibition of bacterial luciferase by anaesthetics
ADEY, G. D., Wardley‐Smith, B., & White, D. (1975) · Life Sciences · doi:10.1016/0024-3205(75)90469-5 · Cited by 24 · see citing works
General anaesthetics and bacterial luminescence I. The effect of diethyl ether on the in vivo light emission of Vibrio fischeri
Middleton, A. J., & Smith, E. B. (1976) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.1976.0037 · Cited by 21 · see citing works
The General Anesthesia Receptor
LaBella, F. S. (1982) · Perspectives in biology and medicine · doi:10.1353/pbm.1982.0051 · Cited by 13 · see citing works

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Abraham, M. H. (1993) · Chemical Society Reviews · doi:10.1039/cs9932200073 · Cited by 2,124 · see citing works
Molecular and cellular mechanisms of general anaesthesia
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General anaesthesia: from molecular targets to neuronal pathways of sleep and arousal
Franks, N. P. (2008) · Nature reviews. Neuroscience · doi:10.1038/nrn2372 · Cited by 1,266 · see citing works
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Purdon, P. L., Sampson, A. L., Pavone, K. J., & Brown, E. N. (2015) · Anesthesiology · doi:10.1097/aln.0000000000000841 · Cited by 869 · see citing works
Mechanisms of Actions of Inhaled Anesthetics
Campagna, J. A., Miller, K. W., & Forman, S. A. (2003) · New England Journal of Medicine · doi:10.1056/nejmra021261 · Cited by 805 · see citing works
Molecular and neuronal substrates for general anaesthetics
Rudolph, U., & Antkowiak, B. (2004) · Nature reviews. Neuroscience · doi:10.1038/nrn1496 · Cited by 771 · see citing works
Crystal structure of firefly luciferase throws light on a superfamily of adenylate-forming enzymes
Conti, E., Franks, N. P., & Brick, P. (1996) · Structure · doi:10.1016/s0969-2126(96)00033-0 · Cited by 620 · see citing works
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Emerging molecular mechanisms of general anesthetic action
Hemmings, H. C., Akabas, M. H., Goldstein, P. A., Trudell, J. R., Orser, B. A., & Harrison, N. L. (2005) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2005.08.006 · Cited by 542 · see citing works
Hydrophobicity and Central Nervous System Agents: On the Principle of Minimal Hydrophobicity in Drug Design
Hansch, C. H., Björkroth, J.-P., & Leo, A. J. (1987) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.2600760902 · Cited by 439 · see citing works
X-ray structures of general anaesthetics bound to a pentameric ligand-gated ion channel
Nury, H., Van Renterghem, C., Weng, Y., Tran, A., Baaden, M., Dufresne, V., Changeux, J.-P., Sonner, J. M., Delarue, M., & Corringer, P.-J. (2011) · Nature · doi:10.1038/nature09647 · Cited by 412 · see citing works
Narcosis Due to Environmental Pollutants in Aquatic Organisms: Residue-Based Toxicity, Mechanisms, and Membrane Burdens
van Wezel, A. P., & Opperhuizen, A. (1995) · Critical Reviews in Toxicology · doi:10.3109/10408449509089890 · Cited by 398 · see citing works
General anaesthetic actions on ligand-gated ion channels
Krasowski, M. D., & Harrison, N. L. (1999) · Cellular and Molecular Life Sciences (CMLS) · doi:10.1007/s000180050371 · Cited by 384 · see citing works
Quantum computation in brain microtubules: decoherence and biological feasibility
Hagan, S., Hameroff, S. R., & Tuszyński, J. A. (2002) · Physical Review E · doi:10.1103/physreve.65.061901 · Cited by 389 · see citing works
Molecular targets underlying general anaesthesia
Franks, N. P. (2006) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0706441 · Cited by 376 · see citing works
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Sonner, J. M., Antognini, J. F., Dutton, R. C., Flood, P. D., Gray, A. T., Harris, R. A., Homanics, G. E., Kendig, J. J., Orser, B. A., Raines, D. E., et al. (2003) · Anesthesia & Analgesia · doi:10.1213/01.ane.0000081063.76651.33 · Cited by 328 · see citing works
Pharmacological Properties of T-Type Ca2+Current in Adult Rat Sensory Neurons: Effects of Anticonvulsant and Anesthetic Agents
Todorovic, S. M., & Lingle, C. J. (1998) · Journal of Neurophysiology · doi:10.1152/jn.1998.79.1.240 · Cited by 318 · see citing works
Stereospecific Effects of Inhalational General Anesthetic Optical Isomers on Nerve Ion Channels
Franks, N. P., & Lieb, W. R. (1991) · Science · doi:10.1126/science.1925602 · Cited by 280 · see citing works
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John, E. R., & Prichep, L. S. (2005) · Anesthesiology · doi:10.1097/00000542-200502000-00030 · Cited by 250 · see citing works
Competitive Inhibition at the Glycine Site of the N -Methyl-d-aspartate Receptor by the Anesthetics Xenon and Isoflurane
Dickinson, R., Peterson, B. K., Banks, P. J., Simillis, C., Martin, J. C. S., Valenzuela, C. A., Maze, M., & Franks, N. P. (2007) · Anesthesiology · doi:10.1097/01.anes.0000287061.77674.71 · Cited by 243 · see citing works
Self-citation
Mapping of general anaesthetic target sites provides a molecular basis for cutoff effects
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Self-citation
Cut-off effects in biological activities of surfactants
Balgavý, P., & Devı́nsky, F. (1996) · Advances in Colloid and Interface Science · doi:10.1016/0001-8686(96)00295-3 · Cited by 237 · see citing works
Molecular Interactions Between Inhaled Anesthetics and Proteins
Eckenhoff, R. G., & Johansson, J. S. (1997) · Pharmacological Reviews · doi:10.1016/s0031-6997(24)01337-1 · Cited by 233 · see citing works
Neural basis of inhalant abuse
Balster, R. L. (1998) · Drug and Alcohol Dependence · doi:10.1016/s0376-8716(98)00078-7 · Cited by 224 · see citing works
Inhibition of protein kinase C by alcohols and anaesthetics
Slater, S. J., Cox, K. J. A., Lombardi, J. V., Ho, C., Kelly, M. B., Rubin, E., & Stubbs, C. D. (1993) · Nature · doi:10.1038/364082a0 · Cited by 224 · see citing works
Structural Basis for the Inhibition of Firefly Luciferase by a General Anesthetic
Franks, N. P., Jenkins, A., Conti, E., Lieb, W. R., & Brick, P. (1998) · Biophysical Journal · doi:10.1016/s0006-3495(98)77664-7 · Cited by 213 · see citing works
Self-citation
The Nature of The Site of General Anesthesia
Miller, K. W. (1985) · International review of neurobiology · doi:10.1016/s0074-7742(08)60555-3 · Cited by 209 · see citing works
Conduction pathways in microtubules, biological quantum computation, and consciousness
Hameroff, S. R., Nip, A. M. L., Porter, M., & Tuszyński, J. A. (2002) · Biosystems · doi:10.1016/s0303-2647(01)00183-6 · Cited by 198 · see citing works
Volatile general anaesthetics activate a novel neuronal K+ current
Franks, N. P., & Lieb, W. R. (1988) · Nature · doi:10.1038/333662a0 · Cited by 199 · see citing works
Self-citation
Glycine and gamma-aminobutyric acid(A) receptor function is enhanced by inhaled drugs of abuse.
Beckstead, M. J., Weiner, J. L., Eger, E. I., Gong, D. H., & Mihic, S. J. (2000) · PubMed · Cited by 195 · see citing works
Enhancement of gamma‐aminobutyric acid‐activated Cl‐ currents in cultured rat hippocampal neurones by three volatile anaesthetics.
Jones, M. V., Brooks, P. A., & Harrison, N. L. (1992) · The Journal of Physiology · doi:10.1113/jphysiol.1992.sp019086 · Cited by 192 · see citing works
Alcohol inhibits cell-cell adhesion mediated by human L1 [published erratum appears in J Cell Biol 1996 Jun;133(5):1139-40]
Ramanathan, R. (1996) · The Journal of Cell Biology · doi:10.1083/jcb.133.2.381 · Cited by 188 · see citing works
Minimum alveolar concentration: ongoing relevance and clinical utility
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Rules for Distinguishing Toxicants That Cause Type I and Type II Narcosis Syndromes
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Volatile anesthetics block intercellular communication between neonatal rat myocardial cells.
Burt, J. M., & Spray, D. C. (1989) · Circulation Research · doi:10.1161/01.res.65.3.829 · Cited by 178 · see citing works
The Neural Circuits Underlying General Anesthesia and Sleep
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How drugs get into cells: tested and testable predictions to help discriminate between transporter-mediated uptake and lipoidal bilayer diffusion
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Partitioning of long-chain alcohols into lipid bilayers: implications for mechanisms of general anesthesia.
Franks, N. P., & Lieb, W. R. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.14.5116 · Cited by 156 · see citing works
Self-citation
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Mechanisms of General Anesthesia
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Self-citation
Mechanisms of Action and Persistent Neuroplasticity by Drugs of Abuse
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Noninvasive biophotonic imaging for studies of infectious disease
Andreu, N., Zelmer, A., & Wiles, S. (2010) · FEMS Microbiology Reviews · doi:10.1111/j.1574-6976.2010.00252.x · Cited by 148 · see citing works
Role of Glutamatergic and GABAergic Systems in Alcoholism
Davis, K. M., & Wu, J. ‐. (2001) · Journal of Biomedical Science · doi:10.1007/bf02255966 · Cited by 148 · see citing works
What is the molecular nature of general anaesthetic target sites?
Franks, N. P., & Lieb, W. R. (1987) · Trends in Pharmacological Sciences · doi:10.1016/0165-6147(87)90160-x · Cited by 145 · see citing works
Self-citation
The molecular mechanisms of general anaesthesia: dissecting the GABAA receptor
Weir, C. J. (2006) · Continuing Education in Anaesthesia Critical Care & Pain · doi:10.1093/bjaceaccp/mki068 · Cited by 143 · see citing works
Binding of the Volatile Anesthetic Chloroform to Albumin Demonstrated Using Tryptophan Fluorescence Quenching
Johansson, J. S. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.29.17961 · Cited by 143 · see citing works
Top-down mechanisms of anesthetic-induced unconsciousness
Mashour, G. A. (2014) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2014.00115 · Cited by 134 · see citing works
The neurobiology of alcohol consumption and alcoholism: An integrative history
Tabakoff, B., & Hoffman, P. L. (2013) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2013.10.009 · Cited by 135 · see citing works
Partitioning of local anesthetics into membranes: surface charge effects monitored by the phospholipid head-group
Seelig, A., ALLEGRINI, P. R., & Seelig, J. (1988) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/0005-2736(88)90070-3 · Cited by 133 · see citing works
The role of nicotinic acetylcholine receptors in the mechanisms of anesthesia
TASSONYI, E., Charpantier, E., Müller, D., Dumont, L., & Bertrand, D. (2002) · Brain Research Bulletin · doi:10.1016/s0361-9230(01)00740-7 · Cited by 129 · see citing works
Integrating the Science of Consciousness and Anesthesia
Mashour, G. A. (2006) · Anesthesia & Analgesia · doi:10.1213/01.ane.0000232442.69757.4a · Cited by 130 · see citing works
Structure-Toxicity Relationships for Industrial Chemicals Causing Type (II) Narcosis Syndrome
Veith, G. D., & Broderius, S. J. (1987) · Springer eBooks · doi:10.1007/978-94-009-3937-0_29 · Cited by 130 · see citing works
The Entwined Mysteries of Anesthesia and Consciousness: Is There a Common Underlying Mechanism?
Hameroff, S. R. (2006) · Anesthesiology · doi:10.1097/00000542-200608000-00024 · Cited by 129 · see citing works
Is a new paradigm needed to explain how inhaled anesthetics produce immobility?
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Liquid General Anesthetics Lower Critical Temperatures in Plasma Membrane Vesicles
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Effect of alcohol on cellular membranes
Goldstein, D. B. (1986) · Annals of Emergency Medicine · doi:10.1016/s0196-0644(86)80120-2 · Cited by 113 · see citing works
Alcohol action on a neuronal membrane receptor: evidence for a direct interaction with the receptor protein.
Li, C., Peoples, R. W., & Weight, F. F. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.17.8200 · Cited by 112 · see citing works
Distribution of Halothane in a Dipalmitoylphosphatidylcholine Bilayer from Molecular Dynamics Calculations
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Anesthetic alterations of collective terahertz oscillations in tubulin correlate with clinical potency: implications for anesthetic action and post-operative cognitive dysfunction
Craddock, T. J. A., Kurian, P., Preto, J., Sahu, K., Hameroff, S. R., Klobukowski, M., & Tuszynski, J. A. (2017) · Scientific Reports · doi:10.1038/s41598-017-09992-7 · Cited by 109 · see citing works
Anaesthetic mechanisms: update on the challenge of unravelling the mystery of anaesthesia
Lugli, A. K., Yost, C. S., & Kindler, C. H. (2009) · European Journal of Anaesthesiology · doi:10.1097/eja.0b013e32832d6b0f · Cited by 105 · see citing works
Glycine and γ-Aminobutyric AcidA Receptor Function Is Enhanced by Inhaled Drugs of Abuse
Beckstead, M. J., Weiner, J. L., Eger, E. I., Gong, D., & Mihic, S. J. (2000) · Molecular Pharmacology · doi:10.1016/s0026-895x(24)23230-2 · Cited by 107 · see citing works
Effects of intravenous anaesthetic agents on fast inhibitory oscillations in the rat hippocampus in vitro
Whittington, M. A., Jefferys, T. G. R., & Traub, R. D. (1996) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1996.tb15633.x · Cited by 105 · see citing works
Probing the Ligand Binding Sites of Fatty Acid and Sterol Carrier Proteins: Effects of Ethanol
Schroeder, F., Myers-Payne, S. C., Billheimer, J. T., & Wood, W. G. (1995) · Biochemistry · doi:10.1021/bi00037a033 · Cited by 104 · see citing works
The nature of sites of general anaesthetic action
Miller, K. W. (2002) · British Journal of Anaesthesia · doi:10.1093/bja/aef167 · Cited by 104 · see citing works
“Volume fraction” correlation for narcosis in aquatic organisms: The key role of partitioning
Abernethyand, S. G., Mackay, D., & McCarty, L. S. (1988) · Environmental Toxicology and Chemistry · doi:10.1002/etc.5620070607 · Cited by 99 · see citing works
New insights into the molecular mechanisms of general anaesthetics
Chau, P.-L. (2010) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2010.00891.x · Cited by 96 · see citing works
Protein Crystallography under Xenon and Nitrous Oxide Pressure: Comparison with In Vivo Pharmacology Studies and Implications for the Mechanism of Inhaled Anesthetic Action
Colloc’h, N., Santos, J. S. O., Retailleau, P., Vivarès, D., Bonneté, F., d’Estaintot, B. L., Gallois, B., Brisson, A. R., Risso, J., Lemaire, M., et al. (2006) · Biophysical Journal · doi:10.1529/biophysj.106.093807 · Cited by 95 · see citing works
Inhibition by steroids of [14C]-guanidinium flux through the voltage-gated sodium channel and the cation channel of the 5-HT3 receptor of N1E-115 neuroblastoma cells
Barann, M., Göthert, M., Brüss, M., & Bönisch, H. (1999) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s002109900089 · Cited by 95 · see citing works
Overview of data and conceptual approaches for derivation of quantitative structure-activity relationships for ecotoxicological effects of organic chemicals
Bradbury, S. P., Russom, C. L., Ankley, G. T., Schultz, T. W., & Walker, J. D. (2003) · Environmental Toxicology and Chemistry · doi:10.1897/01-234 · Cited by 89 · see citing works
Current assessment of targets and theories of anaesthesia
Urban, B. W. (2002) · British Journal of Anaesthesia · doi:10.1093/bja/aef165 · Cited by 89 · see citing works
Amphiphilic sites for general anesthetic action? Evidence from 129Xe-{1H} intermolecular nuclear Overhauser effects
Xu, Y., & Tang, P. S. (1997) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/s0005-2736(96)00184-8 · Cited by 89 · see citing works
Effects of Anesthetics on the Structure of a Phospholipid Bilayer: Molecular Dynamics Investigation of Halothane in the Hydrated Liquid Crystal Phase of Dipalmitoylphosphatidylcholine
Tu, K., Tarek, M., Klein, M. L., & Scharf, D. (1998) · Biophysical Journal · doi:10.1016/s0006-3495(98)77655-6 · Cited by 88 · see citing works
Anaesthetics set their sites on ion channels
Franks, N. P., & Lieb, W. R. (1997) · Nature · doi:10.1038/38614 · Cited by 88 · see citing works
Self-citation
A genetic study of the anesthetic response: mutants of Drosophila melanogaster altered in sensitivity to halothane.
Krishnan, K. S., & Nash, H. A. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.21.8632 · Cited by 87 · see citing works
Interaction of Alcohols and Anesthetics with Protein Kinase Cα
Slater, S. J., Kelly, M. B., Larkin, J. D., Ho, C., Mazurek, A., Taddeo, F. J., Yeager, M. D., & Stubbs, C. D. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.10.6167 · Cited by 86 · see citing works
Anesthetics Act in Quantum Channels in Brain Microtubules to Prevent Consciousness
Craddock, T. J. A., Hameroff, S. R., T. Ayoub, A., Klobukowski, M., & Tuszynski, J. A. (2015) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026615666150225104543 · Cited by 85 · see citing works
Biophysical changes induced by xenon on phospholipid bilayers
Booker, R. D., & Sum, A. K. (2013) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2013.01.016 · Cited by 85 · see citing works
Electrophysiological-mechanical coupling in the neuronal membrane and its role in ultrasound neuromodulation and general anaesthesia
Jérusalem, A., Al‐Rekabi, Z., Chen, H., Ercole, A., Malboubi, M., Tamayo‐Elizalde, M., Verhagen, L., & Contera, S. (2019) · Acta Biomaterialia · doi:10.1016/j.actbio.2019.07.041 · Cited by 85 · see citing works
Cardiac Preconditioning by Volatile Anesthetic Agents: A Defining Role for Altered Mitochondrial Bioenergetics
Stowe, D. F., & Kevin, L. G. (2004) · Antioxidants and Redox Signaling · doi:10.1089/152308604322899512 · Cited by 85 · see citing works
Mechanisms of general anesthesia: from molecules to mind
Mashour, G. A., Forman, S. A., & Campagna, J. A. (2005) · Best practice & research. Clinical anaesthesiology · doi:10.1016/j.bpa.2005.01.004 · Cited by 84 · see citing works
Role of Hydrogen Bonding in General Anesthesia
Abraham, M. H., Lieb, W. R., & Franks, N. P. (1991) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.2600800802 · Cited by 85 · see citing works
Self-citation
Computational predictions of volatile anesthetic interactions with the microtubule cytoskeleton: implications for side effects of general anesthesia
Craddock, T. J. A., St. George, M., Freedman, H., Barakat, K. H., Damaraju, S., Hameroff, S., & Tuszynski, J. A. (2012) · PLoS ONE · doi:10.1371/journal.pone.0037251 · Cited by 84 · see citing works
Spindle disturbances in mammalian cells III. Toxicity, c-mitosis and aneuploidy with 22 different compounds. Specific and unspecific mechanisms
Önfelt, A. (1987) · Mutation Research/Environmental Mutagenesis and Related Subjects · doi:10.1016/0165-1161(87)90067-7 · Cited by 84 · see citing works
Volatile organic compounds inhibit human and rat neuronal nicotinic acetylcholine receptors expressed in Xenopus oocytes
Bale, A. S., Meacham, C. A., Benignus, V. A., Bushnell, P. J., & Shafer, T. J. (2004) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2004.09.011 · Cited by 82 · see citing works
Ethanol increases agonist affinity for nicotinic receptors from Torpedo
Forman, S. A., Righi, D. L., & Miller, K. W. (1989) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/0005-2736(89)90459-8 · Cited by 82 · see citing works
Interactions of anesthetics with their targets: Non-specific, specific or both?
Urban, B. W., Bleckwenn, M., & Barann, M. (2006) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2005.12.005 · Cited by 82 · see citing works
Alcohols Inhibit a Cloned Potassium Channel at a Discrete Saturable Site
Covarrubias, M., Vyas, T. B., Escobar, L. I., & Wei, A. D. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.33.19408 · Cited by 82 · see citing works
Isoflurane and Sevoflurane Interact with the Nicotinic Acetylcholine Receptor Channels in Micromolar Cconcentrations
Scheller, M., Bufler, J., Schneck, H., Kochs, E. F., & Franke, C. (1997) · Anesthesiology · doi:10.1097/00000542-199701000-00016 · Cited by 80 · see citing works
Molecular Mechanisms of Drug Action: An Emerging View
Sonner, J. M., & Cantor, R. S. (2013) · Annual Review of Biophysics · doi:10.1146/annurev-biophys-083012-130341 · Cited by 79 · see citing works
A Unitary Anesthetic Binding Site at High Resolution
Vedula, L. S., Brannigan, G. H., Economou, N. J., Jin, X., Hall, M. A., Liu, R., Rossi, M. J., Dailey, W. P., Grasty, K. C., Klein, M. L., et al. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.017814 · Cited by 78 · see citing works
Primary Alcohols Modulate the Activation of the G Protein-coupled Receptor Rhodopsin by a Lipid-mediated Mechanism
Mitchell, D. C., Lawrence, J. T. R., & Litman, B. J. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.32.19033 · Cited by 78 · see citing works
Understanding of anesthesia – Why consciousness is essential for life and not based on genes
Baluška, F., Yokawa, K., Mancuso, S., & Baverstock, K. F. (2016) · Communicative & Integrative Biology · doi:10.1080/19420889.2016.1238118 · Cited by 76 · see citing works
Role of GABAA receptor subtypes in the behavioural effects of intravenous general anaesthetics
Weir, C. J., Mitchell, S. J., & Lambert, J. J. (2017) · British Journal of Anaesthesia · doi:10.1093/bja/aex369 · Cited by 78 · see citing works
Fluorine-19 NMR spin-spin relaxation (T2) method for characterizing volatile anesthetic binding to proteins. Analysis of isoflurane binding to serum albumin
Dubois, B. W., & Evers, A. S. (1992) · Biochemistry · doi:10.1021/bi00146a007 · Cited by 77 · see citing works
Inhalation Anesthetics
Steffey, E. P., Mama, K. R., & Brosnan, R. J. (2015) · doi:10.1002/9781119421375.ch16 · Cited by 74 · see citing works
Promises and Pitfalls of Quantitative Structure−Activity Relationship Approaches for Predicting Metabolism and Toxicity
Zvinavashe, E., Murk, A. J., & Rietjens, I. M. C. M. (2008) · Chemical Research in Toxicology · doi:10.1021/tx800252e · Cited by 74 · see citing works
Mutations Affecting Sensitivity to Ethanol in the Nematode, Caenorhabditis elegans
Morgan, P. G., & Sedensky, M. M. (1995) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.1995.tb01002.x · Cited by 73 · see citing works
Toxicokinetics of halogenated benzenes in fish: Lethal body burden as a toxicological end point
Sum, D. T. H. M., Schipper, M., & Opperhuizen, A. (1993) · Environmental Toxicology and Chemistry · doi:10.1002/etc.5620120617 · Cited by 71 · see citing works
Mechanisms Involved in Cardiac Sensitization by Volatile Anesthetics: General Applicability to Halogenated Hydrocarbons?
Himmel, H. M. (2008) · Critical Reviews in Toxicology · doi:10.1080/10408440802237664 · Cited by 70 · see citing works
Cellular and Molecular Physiology of Alcohol Actions in the Nervous System
Weight, F. F. (1992) · International review of neurobiology · doi:10.1016/s0074-7742(08)60694-7 · Cited by 68 · see citing works

Seeing the Light
Franks, N. P., Lieb, W. R., & Raja, S. N. (2004) · Anesthesiology · doi:10.1097/00000542-200407000-00034 · Cited by 47 · see citing works
Self-citation
Mechanism of inhibition of bacterial luciferase by anaesthetics
ADEY, G. D., Wardley‐Smith, B., & White, D. (1975) · Life Sciences · doi:10.1016/0024-3205(75)90469-5 · Cited by 24 · see citing works
Molecular mechanisms of general anaesthesia
Franks, N. P., & Lieb, W. R. (1982) · Nature · doi:10.1038/300487a0 · Cited by 436 · see citing works
Self-citation
Do anesthetics act by competitive binding to specific receptors? Phase transition of firefly luciferase1Reported at the Fifth International Conference on the Cellular and Molecular Mechanisms of Anaesthesia, held in Calgary, June 1997.1
Ueda, I., Suzuki, A., & Kamaya, H. (1998) · Toxicology Letters · doi:10.1016/s0378-4274(98)00214-8 · Cited by 4 · see citing works
Effects of general anesthetics on the bacterial luciferase enzyme from Vibrio harveyi: an anesthetic target site with differential sensitivity
Curry, S., Lieb, W. R., & Franks, N. P. (1990) · Biochemistry · doi:10.1021/bi00471a020 · Cited by 48 · see citing works
Self-citation

Authors: Franks, N. P., & Lieb, W. R.
Affiliations: Imperial College London (GB)
King's College London (GB)
ORCID: Franks, N. P.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 1984-08
Volume: 310
Issue: 5978
Pages: 599-601
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/310599a0
OpenAlex: W2028401432
Cited by: 572
References: 24
Citations by year: 2026: 6 · 2025: 11 · 2024: 8 · 2023: 8 · 2022: 9 · 2021: 9 · 2020: 11 · 2019: 12 · 2018: 7 · 2017: 15 · 2016: 12 · 2015: 16 · 2014: 20 · 2013: 21 · 2012: 22
FWCI: 24.22
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Anesthesiology and Pain Medicine › Anesthesia and Sedative Agents
Life Sciences › Neuroscience › Developmental Neuroscience › Anesthesia and Neurotoxicity Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: general anesthetics, competitive binding, firefly luciferase, protein inhibition, competitive inhibition, inhalational anesthetics, halothane, methoxyflurane, chloroform
MeSH terms: Hexanols, Anesthesia, General, Anesthetics, Animals, Coleoptera, Binding Sites, Binding, Competitive, Fatty Alcohols, Halothane, Kinetics, Luciferases, Molecular Conformation, Protein Binding, Protein Conformation

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Do general anaesthetics act by competitive binding to specific receptors?

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