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).


Toxicity Sucrose Hydrate Depression Cage 


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  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

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© Springer Science+Business Media New York 1968

Authors and Affiliations

  • R. I. Ludmer
  • H. C. Sabelli

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