Blockade of the action current in single nodes of ranvier from frog nerve by physostigmine and certain amino derivatives

Abstract

The effects produced by physostigmine and a limited series of aromatic esters derived from cis- and trans-2-dimethylaminocyclohexanol on electrical parameters associated with the action current from the single node preparation of frog sciatic nerve have been briefly studied. In general, the attenuation results of drug action on the single node parallel closely those previously obtained with the polyfiber nerve preparation. Physostigmine attenuates the amplitude of the action current in rough proportion to the concentration of tertiary drug species present in solution, but the diminution in peak height is accompanied by a spreading of the wave on the time axis, leading to an enhanced current-time integral. In contrast, the benzilate and diphenyl acetate esters of the parent cyclic amino alcohols are more powerful than physostigmine in attenuating the nodal action current, approaching the strength of the potent agent veratridine, but they do not simultaneously distort the shape of the residual current curve. Each of the effective current-attenuating agents in the series also produces significant increases in the threshold voltage requirements of the nodal preparation. Both the current attenuations and the threshold changes (except for physostigmine) are fairly readily reversed on removal of the blocking agents. Attempts at correlation of nodal current attenuating strengths with in vitro anticholinesterasic potencies fail markedly in this series of amino alcohol derivatives.