Abstract
It is the intention in this chapter to establish a possible common basis for further discussions on the mechanism of action of local anesthetics. The large variety of compounds having local anesthetic action has made it difficult to clearly establish a common mode of action. This is complicated even more by the fact that local anesthetic activity is often found in combination with other pharmacological actions: agents having antihistaminic, sympathomimetic, parasympathomimetic, antiseptic or antibiotic action in one form or other exhibit a local anesthetic quality.(1–3) Attempts to explain the mechanism of action of such compounds through interference with normal function of enzyme systems or with the general biochemistry of cells have not been too rewarding as there is a considerable discrepancy between electrophysiological and biochemical changes which they produce. The common denominator of all local anesthetic action is the reversible block of electrical activity of nerve fibers without affecting the membrane potential or causing any general toxic action. The pharmacological and neurophysiological mechanisms by which this block is produced may not be the same for the various groups of local anesthetics. To simplify the discussion, one group of local anesthetics used clinically will be discussed in some detail as it seems reasonable that in addition to their close structural relationship their mode of action is probably similar.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
H. Haas, Histamin und Antihistamin, Vols. 1 and 2, Cantor, Aulendorf, Württemberg, Germany (1951–1952).
L. S. Goodman and A. Gilman, The Pharmacological Basis of Therapeutics, Mac-millan, New York (1955).
N. Ludwigs and K. Wiemers, Arch. Exptl. Pathol. Pharmacol. 213:355 (1951).
E. J. Ariens, ed., Molecular Pharmacology, Academic Press, New York (1964).
P. G. Watson, The mode of action of local anesthetics, J. Pharm. Pharmacol. 12:257 (1960).
J. M. Ritchie and P. Greengard, On the mode of action of local anesthetics, Ann. Rev. Pharmacol. 6:405 (1966).
H. F. Zipf, Die Wirkungsmechanismen der Localanasthetica, Pharmaceutica Acta Helvetica 42:480 (1967).
L. Hodgkin and H. E. Huxley, J. Physiol. 117:500 (1952).
L. Hodgkin, Proc. Roy. Soc. Ser. B 148:1 (1958).
J. W. Woodbury, Physiology and Biophysics, Ruch and Patton, eds., Saunders, Philadelphia (1965)
A. L. Hodgkin, The Nature of the Nerve Impulse, p. 108, Univ. Press, Liverpool (1966).
D. Nachmansohn, Chemical and Molecular Basis of Nerve Activity, p. 235, Academic Press, New York (1959).
W-D. Dettbarn, The ACh system in peripheral nerve, Am. N. Y. Acad. Sci. 144, Art. 2, p. 483 (1967).
E. Bartels and D. Nachmansohn, Molecular structure determining the action of local anesthetics on the ACh receptor, Biochem. Z. 342:359 (1965).
A. M. Shanes, W. H. Freygang, H. Grundfest, and E. Amatniek, Anesthetic and calcium action in the voltage-clamped squid giant axon, J. Gen. Physiol. 42:793 (1959).
R. E. Taylor, Effect of procaine on electrical properties of squid axon membrane, Am. J. Physiol. 196:1071 (1958).
G. A. Condouris, A study on the mechanism of action of cocaine on amphibian peripheral nerve, J. Pharmacol. Exptl. Therap. 131243 (1963).
F. A. Davis and W-D. Dettbarn, Depolarizing action of calcium ion depletion on frog nerve and its inhibition by compounds acting on the ACh system, Biochim. Biophys. Acta 63:349 (1962).
A. M. Shanes, Electrochemical aspects of physiological and pharmacological action in excitable cells, I, Pharmacol. Rev. 10:59 (1958).
A. M. Shanes, Electrochemical aspects of physiological and pharmacological action in excitable cells, II, Pharmacol. Rev. 10:104 (1958).
J. Büchi and X. Perlia, Arzneimittel-Forsch 10:1 (1960).
N. Löfgren, Studies on Local Anesthetics, Xilocaine, A New Synthetic Drug, p. 152, Ivor Haeggström, Stockholm (1948).
J. M. Ritchie and P. Greengard, On the active structure of local anesthetics, J. Pharmacol. Exptl. Therap. 133:241 (1961).
W-D. Dettbarn, Active form of local anesthetics, Biochim. Biophys. Acta 57:73 (1962).
T. Narahashi, J. W. Moore, and R. N. Roshin, Anesthetic blocking of nerve membrane conductances by internal and external applications, J. Neurobiology. (In press.)
E. Bartels, Relationship between ACh and local anesthetics, Biochim. Biophys. Acta 109:194(1965).
A. Steinbach, A kinetic model for the action of xilocaine on receptors for ACh, J. Gen. Physiol. 52:162 (1968).
J. F. Danielli and H. Davson, A contribution to the theory of permeability of thin films, J. Cell Comp. Physiol. 5:495 (1935).
J. D. Robertson, The ultrastructure of cell membranes and their derivatives, Biochem. Soc. Symp. 163 (1959).
A. L. Lehninger, The neuronal membrane, Proc. Nat Acad. Sci. 604 (1968).
M. B. Feinstein, Reaction of local anesthetics with phospholipids, J. Gen. Physiol. 48:357 (1964).
M. B. Feinstein and M. Paimre, Specific reaction of local anesthetics with phospho-diester groups, Biochim. Biophys. Acta 115:33 (1965).
M. P. Blaustein and D. Goldman, Action of anionic and cationic nerve-blocking agents: Experiment and interpretations, Science 153:429 (1966).
M. P. Blaustein, Phospholipids as ion exchangers: Implications for a possible role in biological membrane excitability and anesthesia, Biochim. Biophys. Acta 135:653 (1967).
A. W. Cuthbert, Membrane lipids and drug action, Pharmacol. Rev. 19:59 (1967).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1971 Plenum Press, New York
About this chapter
Cite this chapter
Dettbarn, WD. (1971). Local Anesthetics. In: Lajtha, A. (eds) Alterations of Chemical Equilibrium in the Nervous System. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-7175-9_17
Download citation
DOI: https://doi.org/10.1007/978-1-4615-7175-9_17
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4615-7177-3
Online ISBN: 978-1-4615-7175-9
eBook Packages: Springer Book Archive