Abstract
Important constraints on possible molecular mechanisms of general anaesthesia are derived from a quantitative reappraisal of data on the potency of general anaesthetics on whole animals. Despite their popularity, theories that invoke lipids as the prime target do not look at all promising, and available data point much more plausibly to a direct effect on particularly sensitive proteins. Structural changes of proteins on binding general anaesthetics are probably small but may be sufficient to perturb normal function; alternatively, anaesthetics may compete with an endogenous ligand. The phenomenon of pressure reversal of anaesthesia may simply be due to anaesthetics being squeezed away from their target sites.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Richards, C. D. in Topical Reviews in Anaesthesia Vol. 1 (eds Norman, J. & Whitwam, J. G.) Vol. 1, 1–84 (Wright, Bristol, 1980).
Macdonald, A. G. & Wann, K. T. Physiological Aspects of Anaesthetics and Inert Gases (Academic, London, 1978).
Gray, T. C., Nunn, J. F. & Utting, J. E. General Anaesthesia Vol. 1, 4th edn (Butterworths, London, 1980).
Meyer, H. Arch. exp. Path. Pharmak. (Naunyn-Schmiedebergs) 42, 109–118 (1899).
Meyer, H. Arch. exp. Path. Pharmak. (Naunyn-Schmiedebergs) 46, 338–346 (1901).
Overton, E. Studien über die Narkose (Fischer, Jena, 1901).
Franks, N. P. & Lieb, W. R. Nature 274, 339–342 (1978).
Miller, K. W. & Smith, E. B. in A Guide to Molecular Pharmacology-Toxicology Vol. 1 (ed. Featherstone, R. M.) 427–475 (Dekker, New York, 1973).
Steward, A., Allott, P. R., Cowles, A. L. & Mapleson, W. W. Br. J. Anaesth. 45, 282–293 (1973).
Sandorfy, C. Anesthesiology 48, 357–359 (1978).
Mullins, L. J. Chem. Rev. 54, 289–323 (1954).
Cherkin, A. & Catchpool, J. F. Science 144, 1460–1462 (1964).
Mullins, L. J. in A Guide to Molecular Pharmacology-Toxicology Vol. 1 (ed. Featherstone, R. M.) 1–52 (Dekker, New York, 1973).
Hansch, C., Vittoria, A., Silipo, C. & Jow, P. Y. C. J. med. Chem. 18, 546–548 (1975).
Katz, Y. & Simon, S. A. Biochim. biophys. Acta 471, 1–15 (1977).
Miller, K. W., Paton, W. D. M., Smith, E. B. & Smith, R. A. Anesthesiology 36, 339–351 (1972).
Mullins, L. J. in Alterations of Chemical Equilibrium in the Nervous System (ed. Lajtha, A.) 395–421 (Plenum, New York, 1971).
Pringle, M. J., Brown, K. B. & Miller, K. W. Molec. Pharmac. 19, 49–55 (1981).
Lever, M. J., Miller, K. W., Paton, W. D. M. & Smith, E. B. Nature 231, 368–371 (1971).
Halsey, M. J. & Wardley-Smith, B. Nature 257, 811–813 (1975).
Miller, K. W., Paton, W. D. M., Smith, R. A. & Smith, E. B. Molec. Pharmac. 9, 131–143 (1973).
Miller, K. W., Wilson, M. W. & Smith, R. A. Molec. Pharmac. 14, 950–959 (1978).
Moore, W. J. Physical Chemistry 4th edn (Longmans, London, 1963).
Eyring, H., Woodbury, J. W. & D'Arrigo, J. S. Anesthesiology 38, 415–424 (1973).
Miller, K. W. & Wilson, M. W. Anesthesiology 48, 104–110 (1978).
Halsey, M. J., Wardley-Smith, B. & Green, C. J. Br. J. Anaesth. 50, 1091–1096 (1978).
Wardley-Smith, B. & Halsey, M. J. Br. J. Anaesth. 48, 265 (1976).
Kendig, J. J., Schneider, T. M. & Cohen, E. N. J. appl. Physiol. 45, 742–746 (1978).
Kendig, J. J., Schneider, T. M. & Cohen, E. N. J. appl. Physiol. 45, 747–750 (1978).
Meyer, K. H. & Hemmi, H. Biochem. Z. 277, 39–71 (1935).
Allott, P. R., Steward, A., Flook, V. & Mapleson, W. W. Br. J. Anaesth. 45, 294–300 (1973).
Regan, M. J. & Eger, E. I. Anesthesiology 28, 689–700 (1967).
Eger, E. I., Saidman, L. J. & Brandstater, B. Anesthesiology 26, 764–770 (1965).
Steffey, E. P. & Eger, E. I. Anesthesiology 41, 392–396 (1974).
Janoff, A. S., Pringle, M. J. & Miller, K. W. Biochim. biophys. Acta 649, 125–128 (1981).
Diamond, J. M. & Katz, Y. J. Membrane Biol. 17, 121–154 (1974).
Metcalfe, J. C., Seeman, P. & Burgen, A. S. V. Molec. Pharmac. 4, 87–95 (1968).
Franks, N. P. & Lieb, W. R. J. molec. Biol. 133, 469–500 (1979).
Boggs, J. M., Yoong, T. & Hsia, J. C. Molec. Pharmac. 12, 127–135 (1976).
Turner, G. L. & Oldfield, E. Nature 277, 669–670 (1979).
Lieb, W. R., Kovalycsik, M. & Mendelsohn, R. Biochim. biophys. Acta 688, 388–398 (1982).
Rosenberg, P. H., Eibl, H. & Stier, A. Molec. Pharmac. 11, 879–882 (1975).
Pellkofer, R. & Sandhoff, K. J. Neurochem. 34, 988–992 (1980).
Mastrangelo, C. J., Trudell, J. R., Edmunds, H. N. & Cohen, E. N. Molec. Pharmac. 14, 463–467 (1978).
Miller, K. W. & Pang, K. Y. Nature 263, 253–255 (1976).
Richards, C. D. et al. Nature 276, 775–779 (1978).
Neal, M. J., Butler, K. W., Polnaszek, C. F. & Smith, I. C. P. Molec. Pharmac. 12, 144–155 (1976).
Pang, K. Y., Braswell, L. M., Chang, L., Sommer, T. J. & Miller, K. W. Molec. Pharmac. 18, 84–90 (1980).
Finch, E. D. & Kiesow, L. A. Undersea biomed. Res. 6, 41–45 (1979).
Mastrangelo, C. J., Kendig, J. J., Trudell, J. R. & Cohen, E. N. Undersea biomed. Res. 6, 47–53 (1979).
Hill, M. W. Biochim. biophys. Acta 356, 117–124 (1974).
Mountcastle, D. B., Biltonen, R. L. & Halsey, M. J. Proc. natn. Acad. Sci. U.S.A. 75, 4906–4910 (1978).
Kamaya, H., Ueda, I., Moore, P. S. & Eyring, H. Biochim. biophys. Acta 550, 131–137 (1979).
Lee, A. G. Biochemistry 15, 2448–2454 (1976).
Pringle, M. J. & Miller, K. W. Biochemistry 15, 3314–3320 (1979).
Trudell, J. R. Anesthesiology 46, 5–10 (1977).
Skou, J. C. Biochim. biophys. Acta 30, 625–629 (1958).
Clements, J. A. & Wilson, K. M. Proc. natn. Acad. Sci. U.S.A. 48, 1008–1014 (1962).
Bangham, A. D., Standish, M. M. & Miller, N. Nature 208, 1295–1297 (1965).
Ueda, I., Shieh, D. D. & Eyring, H. Anesthesiology 41, 217–225 (1974).
Seeman, P. & Roth, S. Biochim. biophys. Acta 255, 171–177 (1972).
Haydon, D. A., Hendry, B. M., Levinson, S. R. & Requena, J. Nature 268, 356–358 (1977).
Haydon, D. A., Requena, J. & Urban, B. W. J. Physiol., Lond. 309, 229–245 (1980).
McIntosh, T. J., Simon, S. A. & MacDonald, R. C. Biochim. biophys. Acta 597, 445–463 (1980).
Ashcroft, R. G., Coster, H. G. L. & Smith, J. R. Nature 269, 819–820 (1977).
Ebihara, L., Hall, J. E., MacDonald, R. C., McIntosh, T. J. & Simon, S. A. Biophys. J. 28, 185–196 (1979).
Elliott, J. R. & Haydon, D. A. Biochim. biophys. Acta 557, 259–263 (1979).
Reyes, J. & Latorre, R. Biophys. J. 28, 259–279 (1979).
Padron, R., Mateu, L. & Requena, J. Biochim. biophys. Acta 602, 221–233 (1980).
Seeman, P. Pharmac. Rev. 24, 583–655 (1972).
Seeman, P. Experientia 30, 759–760 (1974).
Franks, N. P. & Lieb, W. R. Nature 292, 248–251 (1981).
Kita, Y., Bennett, L. J. & Miller, K. W. Biochim. biophys. Acta 647, 130–139 (1981).
Trudell, J. R. Biochim. biophys. Acta 470, 509–510 (1977).
Seeman, P. Biochim. biophys. Acta 183, 520–529 (1969).
Rand, R. P. & Pangborn, W. A. Biochim. biophys: Acta 318, 299–305 (1973).
Melchior, D. L., Scavitto, F. J. & Steim, J. M. Biochemistry 19, 4828–4834 (1980).
Johnson, S. M. & Bangham, A. D. Biochim. biophys. Acta 193, 92–104 (1969).
Johnson, S. M., Miller, K. W. & Bangham, A. D. Biochim. biophys. Acta 307, 42–57 (1973).
Pang, K., Chang, T. & Miller, K. W. Molec. Pharmac. 15, 729–738 (1979).
Nichols, J. W. & Deamer, D. W. Proc. natn. Acad. Sci. U.S.A. 77, 2038–2042 (1980).
Bangham, A. D. & Mason, W. T. Anesthesiology 53, 135–141 (1980).
Toll, L. & Howard, B. D. Biochemistry 17, 2517–2523 (1978).
Gutknecht, J. & Walter, A. Biochim. biophys. Acta 641, 183–188 (1981).
Nozaki, Y. & Tanford, C. Proc. natn. Acad. Sci. U.S.A. 78, 4324–4328 (1981).
Wishnia, A. & Pinder, T. Biochemistry 3, 1377–1384 (1964).
Ray, A., Reynolds, J. A., Polet, H. & Steinhardt, J. Biochemistry 5, 2606–2616 (1966).
Helmer, F., Kiehs, K. & Hansch, C. Biochemistry 7, 2858–2863 (1968).
Kiehs, K., Hansch, C. & Moore, L. Biochemistry 5, 2602–2605 (1966).
Weber, G. & Young, L. B. J. biol. Chem. 239, 1415–1423 (1964).
Wishnia, A. Biochemistry 8, 5064–5070 (1969).
Schoenborn, B. P. Nature 208, 760–762 (1965).
Wishnia, A. & Pinder, T. W. Biochemistry 5, 1534–1542 (1966).
Sachsenheimer, W., Pai, E. F., Schultz, G. & Schirmer, R. H. FEBS Lett. 79, 310–312 (1977).
Brown, F. F., Halsey, M. J. & Richards, R. E. Proc. R. Soc. B193, 387–411 (1976).
Millar, R. A., Beard, D. J. & Hulands, G. H. Br. J. Anaesth. 43, 1003–1011 (1971).
Miller, J. C. & Miller, K. W. in Physiological and Pharmacological Biochemistry (ed. Blaschko, H. K. F.) 33–76 (Butterworths, London, 1975).
Hulands, G. H., Beard, D. J. & Brammell, A. in Molecular Mechanisms in Anesthesia Vol. 1 (ed. Fink, B. R.) 501–507 (Raven, New York, 1975).
Levitt, J. D. Anesthesiology 42, 267–274 (1975).
Fairhurst, A. S. & Liston, P. Eur. J. Pharmac. 58, 59–66 (1979).
LaBella, F. S., Pinsky, C., Havlicek, V. & Queen, G. in Endogenous and Exogenous Opiate Agonists and Antagonists (ed. Way, E. L.) 71–74 (Pergamon, New York, 1980).
Baker, P. F. & Schapira, A. H. V. Nature 284, 168–169 (1980).
Johnson, F. H., Eyring, H. & Polissar, M. J. The Kinetic Basis of Molecular Biology (Wiley, New York, 1954).
White, D. C. & Dundas, C. R. Nature 226, 456–458 (1970).
Halsey, M. J. & Smith, E. B. Nature 227, 1363–1365 (1970).
Middleton, A. J. & Smith, E. B. Proc. R. Soc. B193, 173–190 (1976).
Ueda, I. & Kamaya, H. Anesthesiology 38, 425–436 (1973).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Franks, N., Lieb, W. Molecular mechanisms of general anaesthesia. Nature 300, 487–493 (1982). https://doi.org/10.1038/300487a0
Issue Date:
DOI: https://doi.org/10.1038/300487a0
This article is cited by
-
High-pressure crystallography shows noble gas intervention into protein-lipid interaction and suggests a model for anaesthetic action
Communications Biology (2022)
-
Anesthetic Alterations of Collective Terahertz Oscillations in Tubulin Correlate with Clinical Potency: Implications for Anesthetic Action and Post-Operative Cognitive Dysfunction
Scientific Reports (2017)
-
Unification, the answer to resemblance questions
Synthese (2017)
-
Moving in extreme environments: inert gas narcosis and underwater activities
Extreme Physiology & Medicine (2015)
-
Intrinsic interaction mode of an inhalation anesthetic with globular proteins: a comparative study on ligand recognition
Colloid and Polymer Science (2011)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.