Role of Water in Drug Action on Nerve

  • R. I. Ludmer
  • H. C. Sabelli


Many investigators have found evidence that water-structure changes play a major role in cellular processes [1–6], However, no general theory concerning the role of water in the action of drugs on excitable tissues exists (except in the case of general anesthetics [7, 81).


Anesthetic Agent Isotope Effect General Anesthetic Heavy Water Conduction Block 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Szent-Györgyi, A.: Bioenergetics, Academic Press, New York, 1957.Google Scholar
  2. 2.
    Baird, S.H., Jr., Karreman, G., Mueller, H., and Szent-Györgyi, A.: Ionic semipermeability as a bulk property, Proc. Natl. Acad. Sci. U.S. 43:705, 1957.CrossRefGoogle Scholar
  3. 3.
    Privalov, P.L.: The state and role of water in biological systems. Biophysics, 3:691, 1958.Google Scholar
  4. 4.
    Klotz, I.M.: in: Kasha, M., and Pullman, B. (eds.), Horizons in Biochemistry, Academic Press, New York, 1962.Google Scholar
  5. 5.
    Eley, D.D.: in: Kasha, M., and Pullman, B. (eds.),Horizons in Biochemistry,Academic Press, New York, 1962.Google Scholar
  6. 6.
    Ling, G.M.: A Physical Theory of the Living State, Blaisdell Publ. Co., New York, 1962.Google Scholar
  7. 7.
    Pauling, L.: A molecular theory of anesthesia. Science 134:15, 1961.PubMedCrossRefGoogle Scholar
  8. 8.
    Miller, S.L.: A theory of gaseous anesthetics, Proc. Natl. Acad. Sci. U.S. 47:1515, 1961.CrossRefGoogle Scholar
  9. 9.
    Butler, T.: Theories of general anesthesia, Pharmacol. Rev. 2:121, 1950.Google Scholar
  10. 10.
    Ferguson, S.: The use of chemical potentials as indices of toxicity, Proc. Roy. Soc. (London) Ser. B 127:387, 1939.CrossRefGoogle Scholar
  11. 11.
    Röntgen, W.K.: Über die Constitution des flüssigen Wassers, Ann. Phys. Chem. (Vienna) 45:91, 1892.CrossRefGoogle Scholar
  12. 11a.
    Latimer, W.M., and Rodebush, W. H.: Polarization and ionization from the standpoint of the Lewis theory of valence, J. Am. Chem. Soc. 42:1419, 1920.CrossRefGoogle Scholar
  13. 12.
    Pauling, L.: in: Hadzi, L. (ed.). Hydrogen Bonding, Pergamon Press Ltd., London, 1959.Google Scholar
  14. 12a.
    Mandelcorn, L.: Clathrates, Chem. Rev. 59:827, 1959.CrossRefGoogle Scholar
  15. 13.
    Frank, H.S., and Wen, W.Y.: Structural aspects of ion solvent interaction in aqueous solutions: A suggested picture of water structure, Discussions Faraday Soc. 24:133, 1957.CrossRefGoogle Scholar
  16. 14.
    Nemethy, G., and Scheraga, H.: Structure of water and hydrophobic bonding in proteins. I. A model for the thermodynamic properties of liquid water, J. Chem. Phys. 36:3382, 1962.CrossRefGoogle Scholar
  17. 15.
    Nemethy, G., and Scheraga, H.: Structure of water and hydrophobic bonding in proteins. IV. The thermodynamic properties of liquid deuterium oxide, J. Chem. Phys. 41:680, 1964.CrossRefGoogle Scholar
  18. 16.
    Marchi, R. P., and Eyring, H.S.: Application of significant structure theory to water, Phys. Chem. 68:221, 1964.CrossRefGoogle Scholar
  19. 17.
    Pople, J. A.: Molecular association in liquids. II. A theory of the structure of water, Proc. Roy. Soc. (London) A205:163, 1951.Google Scholar
  20. 18.
    Carpenter, F.G.: Anesthetic action of inert and unreactive gases on intact animals and isolated tissues. Am. J. Physiol. 178:505, 1954.PubMedGoogle Scholar
  21. 19.
    Bell, R.P., and Wolfenden, J.H.: The association of water and deuterium oxide in dioxan solution, J. Chem. Soc., 1925, p. 822.Google Scholar
  22. 20.
    Swain, C.G., and Bader, R.F.W.: The nature of the structure difference between light and heavy water and the origin of the solvent isotope effect. I, Tetrahedron 10:182, 1960.CrossRefGoogle Scholar
  23. 21.
    Collie, C.H., Hasted, J.B., and Riston, D.M.: The dielectric properties of water and heavy water, Proc. Phys. Soc. (London) 60:145, 1948.CrossRefGoogle Scholar
  24. 22.
    Kavanau, J. Lee: Water and Solute-Water Interactions, Holden-Day, Inc., San Francisco, 1964.Google Scholar
  25. 23.
    Ben-Nairn, A.: On the difference between the thermodynamic behavior of argon in D20 and H2O, J. Chem. Phys. 42:1512, 1965.CrossRefGoogle Scholar
  26. 24.
    Verzar, F., and Haffter, C: Die Wirkung von “schwerem Wasser” (Deuterium Oxyd) auf isolierte Organe, Arch. Ges. Physiol. 236:714, 1935.CrossRefGoogle Scholar
  27. 25.
    Herrman, J.B.: The pharmacological action of deuterium oxide. VIII. Action on the central nervous system, J. Pharmacol. Exptl. Therap. 67:265, 1939.Google Scholar
  28. 26.
    Garby, L., and Nordqvist, P.: The effect of deuterium oxide (heavy water) on conduction velocity in isolated frog nerve. Acta Physiol. Scand. 34:162, 1955.PubMedCrossRefGoogle Scholar
  29. 27.
    Thies, R.E., and Carlson, D.: Conduction velocity in the giant axon of the squid, Biol. Bull. 3:295, 1956.Google Scholar
  30. 28.
    Spyropoulos, C.S., and Ezzy, M.D.: Nerve fiber activity in heavy water. Am. J. Physiol. 197:808, 1959.PubMedGoogle Scholar
  31. 29.
    Sabelli, H.C., and Gorosito, M.: Evidence for biogenic amines receptors in toad sciatic nerve, Intern. J. Neuropharmacol. (in press); see also this volume, p. 101.Google Scholar
  32. 30.
    Toman, J.E.P., and Sabelli, H.C.: Neuropharmacology of earthworm giant fibers, this volume, p. 100.Google Scholar
  33. 31.
    Mitlag, H., Levy, S.C., and Toman, J.E.P.: Efectos Diferenciales de Drogas sobre Ciertos Parametros de Excitabilidad Axonal, II Latin American Congress of Pharmacology, Mexico City, Mexico, October 1965.Google Scholar
  34. 32.
    Glasoe, P.K., and Long, F.A.: Use of glass electrodes to measure activities in deuterium oxide, J. Phys. Chem. 64:188, 1960.CrossRefGoogle Scholar
  35. 33.
    Thomson, J.F.: Biological Effects of Deuterium, The Macmillan Co., New York, 1964.Google Scholar
  36. 33a.
    Lorentede No, R.: A Study of Nerve Physiology. Studies from Rockefeller Institute for Medical Research, 1947, p. 131.Google Scholar
  37. 34.
    Naess, K.: Stimulating effect of ether, Acta Pharmacol. 6:123, 1950.CrossRefGoogle Scholar
  38. 35.
    Wright, E.B.: The effects of asphyxiation and narcosis on peripheral nerve polarization and conduction, Am. J. Physiol. 148:174, 1947.PubMedGoogle Scholar
  39. 35a.
    Schaeffer, H.: Elecktrophysiologie, Franz Deuticke, Vienna, 1940.Google Scholar
  40. 36.
    Condouris, C. A., and Shakalis, A.: The conjoint effects of temperature and local anesthetics on peripheral nerve conduction, Fed. Proc. 26:403, 1967.Google Scholar
  41. 37.
    Tasaki, I., and Spyropoulos, CS.: The influence of changes in temperature and pressure on the nerve fiber, in: Johnson, F. (ed.), The Influence of Temperature on Biological Systems, Am. Physiol. Soc., Washington, D.C., 1957.Google Scholar
  42. 38.
    Condouris, C. A.: A study of the mechanism of action of cocaine on amphibian peripheral nerve, J. Pharmacol. Exptl. Therap. 131:243, 1961.Google Scholar
  43. 39.
    Horowitz, S.B., and Fenichel, I.R.: Diffusion and transport of organic nonelectrolytes in cells, Ann. N.Y. Acad. Sci. 125:572, 1965.PubMedCrossRefGoogle Scholar
  44. 40.
    Catchpool, J.F.: The hydrate microcrystal theory of anesthesia, Ann. N.Y. Acad. Sci. 125:595. 1965.PubMedCrossRefGoogle Scholar
  45. 41.
    Larson, C.P., Jr.: Solubility and partition coefficients, in: Papper, E.M., and Kitz, R.J. (eds.), Uptake and Distribution of Anesthetic Agents, McGraw-Hill, New York, 1963.Google Scholar
  46. 42.
    Markham, A.E., and Kobe, K. A.: Solubility of gases in liquids, Chem. Rev. 28:519, 1941.CrossRefGoogle Scholar
  47. 43.
    Meyer, H.H.: Zur Theorie der Alkohol Narkose. III. Mitt, Der Einfluss wechselnder Temperatur auf Wirkungsstärke und Teilungskoefficient der Narkotica, Arch. Exptl. Pathol. Pharmakol. 46:338, 1901.CrossRefGoogle Scholar
  48. 44.
    Thörner, W.: Untersuchungen über Wärmeerregung und Wärmelähmung und den Erscheinungskomplex der “Gewöhnung” bei der Letzteren, Z. Allgem. Physiol. 18:226, 1920.Google Scholar
  49. 45.
    Shanes, A.M.: Electrochemical aspects of physiological and pharmacological action in excitable cells. Part II, Pharmacol. Rev. 10:165, 1958.PubMedGoogle Scholar
  50. 46.
    Feng, T.P., and Liu, Y.M.: The concentration effect relationship in the depolarization of amphibian nerve by potassium and other agents, J. Cell. Comp. Physiol. 34:33, 1949.CrossRefGoogle Scholar
  51. 47.
    Callego, A.: On the effect of ethyl alcohol upon frog nerve, J. Cell. Comp. Physiol. 31:97, 1948.CrossRefGoogle Scholar
  52. 48.
    Alcock, N.H.: The action of anesthetics on living tissues. Part I. The action on isolated nerve, Proc. Roy. Soc. (London) B77:267. 1906.Google Scholar
  53. 49.
    Shiner, V.S., Jr., Mahler, H.R., Baker, R.H., Jr., and Hiatt, R.R.: Secondary deuterium isotope effects in chemical and biochemical reactions, Ann. N.Y. Acad. Sci. 84:583, 1960.CrossRefGoogle Scholar
  54. 50.
    Halevi, E.A.: The secondary hydrogen isotope effect. Intern. J. Appl. Radiation Isotopes 7:192, 1960.CrossRefGoogle Scholar
  55. 51.
    Elliot, A., and Hanby, W.E.: Deuterium exchange in polypeptides, Nature 182:654, 1958.CrossRefGoogle Scholar
  56. 52.
    Shooter, E.M.: The configuration of proteins in solution, Progr. Biophys. 10:195, 1960.Google Scholar
  57. 53.
    Scheraga, H.A.: Helix-random coil transformations in deuterated macromolecules, Ann. N. Y. Acad. Sci. 84:608, 1960.PubMedCrossRefGoogle Scholar
  58. 54.
    Toman, J.E.P.: Neurotropic drugs, in: Elliott, K.A.C., Page, I.W., and Quastel, J.H. (eds.), Neurochemistry, Charles C. Thomas, Springfield, Illinois, 1962.Google Scholar

Copyright information

© Springer Science+Business Media New York 1968

Authors and Affiliations

  • R. I. Ludmer
  • H. C. Sabelli

There are no affiliations available

Personalised recommendations