[The effect of aminobenzoic acid derivatives on the ion current of myelinated neurons. 2. Inactivation of sodium permeability]. / Wirkung von Aminobenzoesäure-Derivaten auf die Ionenströme myelinisierter Nervenfasern. 2. Mitteilung: Inaktivierung der Natrium-Permeabilität.

Effects of Aminobenzoic Acid Derivatives on the Ionic Currents in Myelinated Nerve/2nd Communication: Sodium inactivation. Derivatives of aminobenzoic acid similar to metacaine were modified and their effects on the sodium inactivation and on the sodium permeability constant, PNa, of single potential clamped myelinated nerve fibres were tested. Comparing the observed shift of the inactivation curves and the reduction of PNa with the octanol/water partition coefficients of the drugs tested, a minimum lipid solubility seems to be necessary for the substances being efficacious. It is assumed that the uncharged aminobenzoic acids reduce PNa by disturbing the lipid matrix in an unspecific manner. The observed shift of the inactivation curves is explained in terms of the fixed charges at the inside of the membrane being moved apart by the uncharged compounds thus lowering the effective membrane potential. Moreover, no indications for a receptor-mediated mechanism were found.

[The action of aminobenzoic acid derivatives on the ion currents in myelinated nerves. 1. Dose-response relationship]. / Wirkung von Aminobenzoesäure-Derivaten auf die Ionenströme myelinisierter Nervenfasern. 1. Mitteilung: Dosis-Wirkungs-Beziehungen.

Effects of Aminobenzoic Acid Derivatives on the Ionic Currents in Myelinated Nerve/1st Communication: Dose-response curves Derivatives of aminobenzoic acid were modified and their blocking potencies on the ionic currents of single potential clamped myelinated nerve fibres were tested by means of dose-response curves. Starting from metacaine (ethyl m-aminobenzoate), derivatives of different basicity were produced by N-dimethylization, N-quarternization and by preparing a corresponding aliphatic amine. The corresponding free acids and the structural isomers of metacaine were tested as well. The physico-chemical properties of the derivatives were characterized by their pKa-values and their octanol/water partition coefficients. Our findings suggest that the site of action of the aminobenzoic acids tested is located at the inside of the nerve membrane. Moreover, no indications of binding to a receptor in a pharmacological sense were found.