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N.T. PARKHOMENKO, L.N. YATSENKO, N.G. HIMMELREICH (2020) 'USE DEPENDENT BLOCK OF SODIUM CHANNELS BY LOCAL ANESTHETICS IS BASED ON PI-PI AROMATIC INTERACTION' in O.A. Krishtal, E.A. Lukyanetz (Eds.), ESSAYS ON NEUROPHYSIOLOGY BY PLATON KOSTYUK AND HIS STUDENTS, AKADEMPERIODYKA, pp. 82-86

USE DEPENDENT BLOCK OF SODIUM CHANNELS BY LOCAL ANESTHETICS IS BASED ON PI-PI AROMATIC INTERACTION

N.T. PARKHOMENKO, L.N. YATSENKO, N.G. HIMMELREICH

    Palladin Institute of Biochemisrty, Ukraine
DOI: https://doi.org/10.15407/biph.books.EssNeur.082


Abstract

Sodium current (INa) inhibition by prototypical local anesthetics (bupivacaine, lidocaine, and other "caines"), nonsedative anticonvulsants (phenytoin, carbamazepine and lamotrigine), antidepressant (amitriptyline), and anti-arrhythmic (amiodarone) have two modes and some have been operationally defined: use-dependent or phasic block, measured as a decrease in INa during repetitive activation, and tonic block, measured as INa decrease in the preceding activation absence. The molecular mechanisms accounting for the voltage- and use-dependent block of sodium channels by these drugs, despite intensive and profound investigations, have remained elusive.

Keywords: Sodium channel inhibition, local anesthetics, use-dependent block, voltage-dependent block, ion channel kinetics, aromatic-aromatic interactions, drug binding energy, electrophysiology, sodium channel subtypes, ion channel pharmacology.

Full text: (PDF, in English)

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