Abstract

The action of hexafluorenium (HFL) and certain other agents has been studied using the sartorius muscle-sciatic nerve preparation of the frog. Indirect stimulation was used to produce muscle twitches.

In the indirectly stimulated muscle, HFL reduces the twitch tension without preceding twitch potentiation. The twitch depression is reversible; it amounts to 10% with HFL 5 x 10^-6 M and it increases to 100% with HFL 30 x 10^-6 M. In terms of twitch tension reduction HFL is approximately 15x weaker than d-tubocurarine (dTC).

The fall in twitch tension produced by HFL 20 x 10^-6 M is not antagonized by edrophonium (lO to 5O x 1O^-6 M).

HFL (10 x 10^-6 M) causes marked inhibition of the depolarizing action of acetyicholine on the postjunctional membrane.

HFL (10 x 10^-6 M) does not cause any change in the resting potential of the postjunctional membrane. This concentration of HFL produces an increase in the amplitude and rate of repolarization of action potentials neurally initiated at the endplate. The maximum rate of rise of the endplate potential is significantly reduced. No significant change in the critical membrane potential occurs.

In junctions where transmission is blocked by HFL (10 to 30 x 10^-6 M) the endplate potential is reduced in amplitude and its time course parallels that seen at junctions blocked with d-tubocurarine.

In preparations treated with HFL (5 x 10^-6 M) addition of succinylcholine (SCh) (1.25 to 5 x 10^-6 M) and carbamyicholine (11 x 10^-6 M) causes a fall in twitch tension with little or no preceding twitch potentiation.

In preparations treated with fluorenyltri-methylammonium (FTMA) (50 x 10^-6 M) addition of SCh (5 x 10^-6 M) causes a fall in twitch tension which is preceded by a small twitch potentiation.

In preparations treated with dTC (0.36 x 10^-6 M) the twitch tension falls about 15%. Addition of SCh (5 x 10^-6 M) increases the twitch tension to above control levels.

A fall in twitch tension produced by HFL (5 x 10^-6 M) plus SCh (2.5 x 10^-6 M) is not antagonized by edrophonium (50 x 10^-6 M).

In certain respects the neuromuscular block produced by HFL superficially resembles that produced by dTC but other evidence indicates that these agents do not act in a parallel manner. A scheme is presented in which it is suggested that HFL blocks the mechanism by which the postjunctional membrane becomes depolarized when receptor sites become activated by agents such as ACh. Our results help to explain the clinical observation that HFL augments the neuromuscular block produced by intravenously administered SCh.