Working Mechanisms of Anaesthetic Agents

  • M. Dzoljic
Conference paper


These words were the opening of Hans Meyer’s lecture dealing with the working mechanism of anaesthetic agents, at the Harvey Society on 7th October 1905. The words were, at that time, as relevant as they are now. Many are still attracted by this problem and, indeed, with all the progress that is made in biochemistry, biophysics as well as cell biology this problem still presents a great challenge. Nevertheless, since the formulation of first theories on anaesthetic action in the Middle Ages (or perhaps antiquity), much improvement on theoretical ground has been achieved. This is specially true for the intravenous anaesthetics [1, 21 but less obvious for the volatile anaesthetic drugs. The working mechanism of volatile anaesthetics is still a topic of extensive research that is build upon a long history of thinking about neuronal function.


Anaesthetic Agent Volatile Anaesthetic Minimum Alveolar Concentration Anaesthetic Effect Anaesthetic Action 
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  1. 1.
    Mastronardi P, Cafiero T, Rossi AE (1999) Hypnotics. In: Gullo A (ed) Anaesthesia, Pain, Intensive Care and Emergency Medicine–A.P.I.C.E. Springer, Milano, pp 185–191Google Scholar
  2. 2.
    Dzoljic M, Gelb AW (1997) Intravenous anaesthetics: some cellular sites of action. Eur J Anaesthesiol [Suppl] 15: 3–7CrossRefGoogle Scholar
  3. 3.
    Koblin DD, Eger EII, Johnson BH et al (1981) Minimum alveolar concentration and oil/gas partitition coefficients of four anesthetic isomers. Anesthesiol 54: 314–331CrossRefGoogle Scholar
  4. 4.
    Mullins U (1954) Some physical mechanisms in narcosis. Chem Rev 54: 289–323CrossRefGoogle Scholar
  5. 5.
    Macdonald AG, Ramsey RL (1995) The effects of nitrous oxide on a glutamate-gated ion channel and their reversal by high pressure; a single channel analysis. Biochim Biophys Acta 1236: 135–141PubMedCrossRefGoogle Scholar
  6. 6.
    Miller KW, Paton WDM, Smith RA, Smith EB (1973) The pressure reversal of general anesthesia and the critical volume hypothesis. Mol Pharmacol 9: 131–143PubMedGoogle Scholar
  7. 7.
    Franks NP, Lieb WR (1984) Do general anaesthetics act by competitive binding to specific receptors? Nature 310: 599–601PubMedCrossRefGoogle Scholar
  8. 8.
    Cantor RS (1998) The lateral pressure profile in membranes: a physical mechanism of general anesthesia. Toxicol Lett 100–101: 451–458CrossRefGoogle Scholar
  9. 9.
    Krnjevic K (1991) Cellular mechanisms of anesthesia. Ann NY Acad Sci 625: 1–16PubMedCrossRefGoogle Scholar
  10. 10.
    Urban BW (1993) Differential effects of gaseous and volatile anaesthetics on sodium and potassium channels. Br J Anaesth 71: 25–38PubMedCrossRefGoogle Scholar
  11. 11.
    Terrar DA (1993) Structure and function of calcium channels and the actions of anaesthetics. Br J Anaesth 71: 39–46PubMedCrossRefGoogle Scholar
  12. 12.
    Franks NP, Lieb WR (1993) Selective actions of volatile general anaesthetics at molecular and cellular levels. Br J Anaesth 71: 65–76PubMedCrossRefGoogle Scholar
  13. 13.
    Xie Z, Commissaris RL (1992) Anxiolytic-like effects of the noncompetitive NMDA antagonist MK801. Pharmacol Biochem Behav 43: 471–477PubMedCrossRefGoogle Scholar
  14. 14.
    Anis NA, Berry SC, Burton NR, Lodge D (1983) The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N-methyl-aspartate. Br J Pharmacol 79: 565–575PubMedCrossRefGoogle Scholar
  15. 15.
    Lovinger DM, White G, Weight FF (1989) Ethanol inhibits NMDA-activated ion current in hippocampal neurons. Science 243: 1721–1724PubMedCrossRefGoogle Scholar
  16. 16.
    Yang J, Zorumski CF (1991) Effects of isoflurane on N-methyl-D-aspartate gated ion channels in cultured rat hippocampal neurons. Ann NY Acad Sci 625: 287–289PubMedCrossRefGoogle Scholar
  17. 17.
    Jevtovic-Todorovic V, Todorovic SM, Mennerick S et al (1998) Nitrous oxide (laughing gas) is an NMDA antagonist, neuroprotectant and neurotoxin. Nat Med 4: 460–463PubMedCrossRefGoogle Scholar
  18. 18.
    Daniell LC (1995) Effect of volatile general anesthetics and n-alcohols on glutamate-stimulated increases in calcium ion flux in hippocampal membrane vesicles. Pharmacology 50: 154–161PubMedCrossRefGoogle Scholar
  19. 19.
    Franks NP, Lieb WR (1994) Molecular and cellular mechanisms of general anaesthesia. Nature 367: 607–614PubMedCrossRefGoogle Scholar
  20. 20.
    Aguayo LG, Pancetti FC (1994) Ethanol modulation of the y-aminobutyric acidA- and glycine-activated Cl-current in cultured mouse neurons. J Pharmacol Exp Ther 270: 61–69PubMedGoogle Scholar
  21. 21.
    Jones MV, Brooks PA, Harrison NL (1992) Enhancement of y-aminobutyric acid-activated Cl-currents in cultured rat hippocampal neurones by three volatile anaesthetics. J Physiol (London) 449: 279–293Google Scholar
  22. 22.
    Hara MM, Kai Y, Ikemoto Y (1994) Enhancement by propofol of the y-aminobutyric acidA response in dissociated hippocampal pyramidal neurons of the rat. Anesthesiol 81: 988–993CrossRefGoogle Scholar
  23. 23.
    Uchida I, Kamatchi G, Burt D, Yang J (1995) Etomidate potentiation of GABAA receptor gated current depends on subunit composition. Neurosci Lett 185: 203–206PubMedCrossRefGoogle Scholar
  24. 24.
    Krishek BJ, Xie X, Blackstone C et al (1994) Regulation of GABAA receptor function by protein kinase C phosphorylation. Neuron 12: 1081–1095PubMedCrossRefGoogle Scholar
  25. 25.
    Fanant M, Cull-Candy S (1993) GABA receptors, granule cells and genes. Nature 361: 302–303CrossRefGoogle Scholar
  26. 26.
    Wafford KA, Whiting PJ (1992) Ethanol potentiation of GABAA receptors requires phosphorylation of the alternatively spliced variant of the y2 subunit. FEBS Lett 313: 113–117PubMedCrossRefGoogle Scholar
  27. 27.
    Weiner JL, Zhang L, Carlen PL (1994) Potentiation of GABAA-mediated synaptic current by ethanol in hippocampal CAI neurons: possible role of protein kinase C. J Pharmacol Exp Ther 268: 1388–1395PubMedGoogle Scholar
  28. 28.
    Harris RA, McQuilkin JS, Paylor R et al (1995) Mutant mice lacking the y isoform of protein kinase C show decreased behavioral actions of ethanol and altered function of y-aminobutyrate type A receptors. Proc Natl Acad Sci USA 92: 3658–3662PubMedCrossRefGoogle Scholar
  29. 29.
    Koblin DD (1994) Mechanisms of action. In: Miller RD (ed) Anesthesia. 4th edn. Churchill Livingstone, New York, pp 67–99Google Scholar

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© Springer-Verlag Italia 2000

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  • M. Dzoljic

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