PHARMACOLOGICAL ACTION OF TETR A- ALKYL- AMMONIUM COMPOUNDS. 513 



methyl and tetra- ethyl -ammonium chloride, as there is no evidence for the assump- 

 tion that the methyl and ethyl groups act independently. It is, however, equally 

 difficult to explain the differences between these two substances on any theory which 

 has been put forward. One only will be referred to. Hober and Waldenberg,* 

 from a study of the demarcation currents and the irritability of frog's muscles under 

 the influence of tetra-methyl-ammonium chloride and tetra-ethyl-ammonium chloride, 

 conclude that the change of irritability depends, as they believe it does, in the case 

 of alkali salts, upon changes in the colloidal condition of the " Plasmahaut " ; and that 

 the changes in the electrical behaviour of the muscles are an expression of the 

 alterations in the permeability of this layer occurring in consequence of the colloidal 

 change induced. That an action of this kind probably occurs seems to follow from 

 some preliminary experiments I made on the haemolysis of blood corpuscles. Frog's 

 blood diluted with tetra-methyl-ammonium chloride in distilled water down to one- 

 fifth isotonic did not undergo haemolysis readily, and the corpuscles showed changes 

 similar to those seen after treatment with boric acid solutions. The effects were 

 less marked with tetra-ethyl-ammonium chloride solutions. On the other hand, 

 corpuscles from defibrinated mammalian blood, separated and washed, were haemo- 

 lysed by hypotonic solutions of tetra-methyl-ammonium chloride almost as readily as 

 with corresponding strengths of sodium chloride. No gross changes were produced 

 by the addition of isotonic solutions of tetra-methyl-ammonium chloride to the 

 separated serum. But although a change in the colloidal condition of the external 

 layer of the muscle cells may occur and may account for the absence of contracture 

 when a freshly excised sartorius is immersed in a solution of tetra-methyl-ammonium 

 chloride, and, as Hober and Waldenberg suggest, for the toxic effect of isotonic 

 solutions on the contractile substance of the muscle, it is difficult to explain the 

 paralysing action of quaternary compounds and the differences in action of tetra- 

 methyl-ammonium chloride and tetra-ethyl-ammonium chloride on this theory. It 

 does not seem to me that the manner of action as distinct from the place of action 

 of these paralysing substances can at present be formulated with any advantage. 

 Not only is the chemical composition of the substance or substances on which these 

 drugs act unknown to us, but the composition of the drugs themselves is also so 

 varied that no possible chemical reaction common to all of them seems deducible 

 from it. The fact that quaternary compounds, which are saturated compounds and 

 for the most part stable, exhibit in its purest form a paralysing action on the myo- 

 neural junction suggests an action largely physical in character ; but the specificity of 

 the effect in some cases and the great variation shown by different compounds point, 

 on the other hand, to changes of a chemical nature. At present we do not seem 

 able to go further than state the action of these substances in the physiological 

 terms of stimulation and depression. How these are brought about further research 

 may show. 



* Pfluger's Arch., cxxvi. p. 331 [1909]. 

 TRANS. ROY. SOC. EDIN., VOL. L. PART II. (NO. 17). 73 



