Pharmacologic Regulation of Local Anesthetic Conduction Block by Cyclic AMP

  • B. J. Kraynack
Conference paper
Part of the Anaesthesiologie und Intensivmedizin / Anaesthesiology and Intensive Care Medicine book series (A+I, volume 176)

Abstract

The phenomenon of tachyphylaxis (acute tolerance) is generally explained on the basis of the physicochemical properties of local anesthetic agents. The most popular concept suggests that there is a reduction in the amount of free base available for block due to a progressive decrease in local pH. An alternative hypothesis suggests that tachyphylaxis may be due to a true reduction in effect of the local anesthetic at the receptor level. Further progress in understanding the molecular basis of tachyphylaxis requires identification of the events at the membrane level that are responsible for controlling ionic flux. Although it is well-established that local anesthetic agents produce nondepolarizing conduction block by inhibiting sodium ion flux through axonal membrane sodium channels, the specific biochemical events governing the process remain unknown. Previous studies have shown that adenosine 3´, 5´cyclic monophosphoric acid (cyclic AMP) is a key factor in the regulation of narcosis [1]. The lipid soluble, phosphodiesterase-resistant 6-N, 2-0, dibutyryl analog of cyclic AMP (db-cyclic AMP) when administered intracerebroventricularly, dose-dependently shortened narcosis induced by amobarbital [2] and a wide variety of anesthetic, sedative-hypnotic, and tranquilizer agents [3]. It was of interest to determine whether the dibutyryl analog of cyclic AMP and other adenine nucleotides regulate conduction anesthesia as well.

Keywords

Adenosine Lidocaine Ketamine Theophylline Bupivacaine 

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References

  1. 1.
    Cohn ML (1975) Cyclic AMP, thryrotropin-releasing factor and somatostatin: key factors in the regulation of the duration of narcosis. In Fink BR (ed) Molecular mechanisms of anesthesia. Raven, New York, pp 485.Google Scholar
  2. 2.
    Cohn ML, Yamaoka H, Taylor FH, Kraynack B (1973) Action of intracerebroventricular dibutyryl cyclic AMP on amobarbital anaesthesia in rats. Neuropharmacology 12:401.PubMedCrossRefGoogle Scholar
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    Cohn ML, Cohn M, Taylor FH, Scattaregia F (1975) A direct effect of dibutyryl cyclic AMP on the duration of narcosis induced by sedative, hypnotic, tranquilizer and anaesthetic drugs in the rat. Neuropharmacology 14:483.PubMedCrossRefGoogle Scholar
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    Kraynack BJ, Gintautas J (1982) Reversal of procaine conduction blockade by adenine nucleotides in vivo and in vitro. Acta Anaesthesiol Scand 26:334PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1986

Authors and Affiliations

  • B. J. Kraynack

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