Skip to main content
Log in

Four applications of the anesthetic cut-off effect

  • Published:
Bulletin of Mathematical Biology Aims and scope Submit manuscript

Abstract

This article presents and analyses several cases in which the use of the cut-off effect is useful. It starts from the fact that an anesthetic effect of homologous agents is always expressible as a function of their chain lengths and that the cut-off point is a point at which the function vanishes. We then investigate four categories of results: (i) whole body effects. (ii) Cases in which the anesthetics affect the Hodgkin-Huxley parameters of a nerve. (iii) Molecular mechanisms of anesthetic action. (iv) The physical chemistry of the anesthetic process. Our discussion shows that it is possible to incorporate these apparently remote results into one framework. It also shows how to compare results that were gathered by independent measuring methods. In some instances we suggest an interpretation, in others we suggest a further gathering of experimental data. One of the deductions indicates that a weakness exists in the lipid theories of anesthesia.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Abadji, V. C., D. E. Raines, A. Watts and K. W. Miller (1993). The effect of general anesthetics on the dynamics of phosphatidylcholine-acetylcholine receptor interactions in reconstituted vesicles. Biochim. Biophys. Acta 1147, 143–153.

    Article  Google Scholar 

  • Arbib, M. (1995). Handbook of Brain Theory and Neural Network, MIT Press.

  • Barton, A. F. M. (1983). Handbook of Solubility Parameters and Other Cohesion Parameters, Boca Raton, FL: CRC Press.

    Google Scholar 

  • Devinsky, F., A. Kopecka-Leitmanova, F. Serensen and P. Balgavy (1990). Cut-off effect in antimicrobial activity and membrane perturbation efficiency of the homologous series of N,N-dimethylalkylamine oxides. J. Pharm. Pharmacol. 42, 790–794.

    Google Scholar 

  • Elliott, J. R., R. D. Murrell and D. A. Haydon (1987). Local anesthetic action of carboxylic esters: evidence for the significance of molecular volume and for the number of sites involved, J. Membr. Biol. 95, 143–149.

    Article  Google Scholar 

  • Forman, S. A. and K. W. Miller (1989). Molecular sites in postsynaptic nicotinic membranes. Trends Pharmacol. Sci. 10, 447–452.

    Article  Google Scholar 

  • Franks, N. P. and W. R. Lieb (1982). Molecular mechanisms of general anesthesia. Nature 300, 487–493.

    Article  Google Scholar 

  • Franks, N. P. and W. R. Lieb (1985). Mapping of general anesthetic target sites provides a molecular basis for cut-off effects. Nature 316, 349.

    Article  Google Scholar 

  • Franks, N. P. and W. R. Lieb (1986). Partitioning of long chain alcohols into lipid bilayers: Implications for mechanisms of general anesthesia. Proc. Natl. Acad. Sci. 83, 5116–5120.

    Article  Google Scholar 

  • Franks, N. P. and W. R. Lieb (1987). What is the molecular nature of general anesthetic target sites? Trends Pharmacol. Sci. 8, 169–174.

    Article  Google Scholar 

  • Franks, N. P. and W. R. Lieb (1994). Molecular and cellular mechanisms of general anesthesia. Nature 367, 607–614.

    Article  Google Scholar 

  • Goodman, L. S. and A. Gilman (1970). The Pharmacolgical Basis of Therapeutics, New York: Macmillan.

    Google Scholar 

  • Guggenheim, E. A. (1959). Thermodynamics, New York: North-Holland.

    Google Scholar 

  • Halsey, M. J. (1984). A reassessment of the molecular structure-functional relationships of the inhaled general anesthetics. Br. J. Anaesth. 56, 9S–25S.

    Google Scholar 

  • Hitzemann, R. J. (1989). Effects of nonelectrolyte molecules with anesthetic activity on the physical properties of DMPC multilayer liposomes. Biochim. Biophys. Acta 983, 205–211.

    Article  Google Scholar 

  • Ionescu, P., B. S Chortkoff and T. Hudlicky (1995). Molecular properties of the ‘ideal’ inhaled anesthetic: studies of fluorinated methanes, ethanes, propanes, and butanes. Anesth. Analg. 80, 848.

    Google Scholar 

  • Janes, N., J. W. Hsu, E. Rubin and T. F. Taraschi (1992). Nature of alcohol and anesthetic action on cooperative membrane equilibria. Biochemistry 31, 9467–9472.

    Article  Google Scholar 

  • Janoff, A. S., M. J. Pringle and K. W. Miller (1981). Correlation of general anesthetic potency with solubility in membranes. Biochim. Biophys. Acta 649, 125–128.

    Article  Google Scholar 

  • Kaminoh, Y., S. Nishimura, H. Kamaya and I. Ueda (1992). Alcohol interaction with high entropy states of macromolecules: critical temperature hypothesis for anesthesia cut-off. Biochim. Biophys. Acta 1106, 335–343.

    Article  Google Scholar 

  • Katz, Y. (1988). On the use of regular solution theory as a theoretical frame for the analysis of membrane phenomena. Biochim. Biophys. Acta 939, 19–28.

    Article  Google Scholar 

  • Katz, Y. (1994a). Anesthesia and the Meyer-Overton rule I. Potencies and perturbations. J. Theor. Biol. 167, 93–97.

    Article  Google Scholar 

  • Katz, Y. (1994b). Anesthesia and the Meyer-Overton rule II. A solution theory view of anesthesia and perturbation. J. Theor. Biol. 167, 99–105.

    Article  Google Scholar 

  • Liu, J., M. J. Laster, D. D. Koblin, E. I. Eger II, M. J. Halsey, S. Taheri, and B. Chortkoff (1994). A cut-off in potency exists in the perfluoroalkanes. Anesth. Analg. 79, 238–244.

    Google Scholar 

  • Liu, J., M. J. Laster, S. Taheri, E. I. Eger II, D. D. Koblin and M. J. Halsey, (1993). Is there a cut-off in anesthetic potency for the normal alkanes? Anesth. Analg. 77, 12–18.

    Google Scholar 

  • Lopes, C. M. and S. R. Louro (1991). The effect of n-alkanols on the lipid/protein interface of Ca-ATPase of sarcoplasmic reticulum vesicles. Biochim. Biophys. Acta 1070, 467–473.

    Article  Google Scholar 

  • McIntosh, T. J., S. A. Simon and R. C. MacDonald (1980). The organization of n-alkanes in lipid bilayers. Biochim. Biophys. Acta 597, 445–463.

    Article  Google Scholar 

  • Miller, K. W., L. L. Firestone, J. K. Alifimoff and P. Streicher (1989). Nonanesthetic alcohols dissolve in synaptic membranes without perturbing their lipids. Proc. Natl. Acad. Sci. 86, 1084–1087.

    Article  Google Scholar 

  • Mullins, L. J. (1973). Guide to Molecular Pharmacology-Toxicology, Featherstone (Ed.), New York: Dekker, pp. 1–52.

    Google Scholar 

  • Mullins, L. J. (1991). Viewing anesthesia research 1954–1990. Ann. New York Acad. Sci. 625, 841–844.

    Google Scholar 

  • Pope, J. M., L. A. Littlemore and P. W. Westerman (1989). Chainlength dependence of n-alkane solubility in phosphatidylcholine bilayers: a 2H-NMR study. Biochim. Biophys. Acta 980, 69–76.

    Article  Google Scholar 

  • Prigogine, I. (1957). The Molecular Theory of Solutions, New York: North-Holland.

    Google Scholar 

  • Pringle, M. J., K. B. Brown and K. W. Miller (1981). Can the lipid theories of anesthesia account for the cut-off in anesthetic potency in homologous series of alcohols? Mol. Pharm. 19, 49–55.

    Google Scholar 

  • Puil, E. and B. Gimbarzevsky (1987). Modifications in membrane properties of trigeminal sensory neurons during general anesthesia. J. Neurophysiol. 58, 87–104.

    Google Scholar 

  • Reiss, H. (1985). Adv. Chem. Phys. 9, 1–83.

    Google Scholar 

  • Roth, S. H. (1979). Physical mechanisms of anesthesia. Ann. Rev. Phamacol. Toxicol. 19, 159–178.

    Article  Google Scholar 

  • Schroeder, F., W. J. Morrison, C. Gorka and W. G. Wood (1988). Biochim. Biophys. Acta 946, 85–94.

    Article  Google Scholar 

  • Smith, W. D., R. C. Dutton and N. T. Smith (1996). Measuring the performance of anesthetic depth indicators. Anesthesiology 84, 38–51.

    Article  Google Scholar 

  • Tinklenberg, J. A., I. S. Segal, G. Tianzhi and M. Maze (1991). Analysis of anesthetic action on the potassium channels of the Shaker mutant of Drosophila. Ann. New York Acad. Sci. 625 532–539.

    Google Scholar 

  • Wann, K. T. and A. G. Macdonald (1988). Actions and interactions of high pressure and general anesthetics. Prog. Neurobiol. 30, 271–307.

    Article  Google Scholar 

  • Westerman, P. W. and J. M. Pope (1991). Ordering and stability of alkanes and alkanols in phospholipid bilayers: a 2H-NMR study of the cut-off effect. Ann. New York Acad. Sci. 625, 757–759.

    Google Scholar 

  • Westerman, P. W., J. M. Pope, N. Phonphok, J. W. Doane and D. W. Dubro (1988). The interaction of n-alkanol with lipid bilayer membranes: a 2H-NMR study. Biochim. Biophys. Acta 939, 64–78.

    Article  Google Scholar 

  • Wick, M. J., S. J. Mihic, S. Ueno, M. P. Mascia, J. R. Trudell, S. J. Brozowski, Q. Ye, N. l. Harrison and J. R. Harris (1998). Mutations of GABA and Gly receptors change alcohol cut-off: evidence for an alcohol receptor? Proc. Natl. Acad. Sci. 95, 6504–6509.

    Article  Google Scholar 

  • Wood, S. C., S. A. Forman, and K. W. Miller (1991). Short chain and long chain alkanols have different sites of action on nicotinic acetylcholine receptor channels from torpedo. Mol. Pharmacol. 39, 332–338.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Katz, Y., Aharon, I. Four applications of the anesthetic cut-off effect. Bull. Math. Biol. 62, 1–16 (2000). https://doi.org/10.1006/bulm.1999.0098

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1006/bulm.1999.0098

Keywords

Navigation