PHARMACOLOGICAL ACTION OF TETRA-ALKYL- AMMONIUM COMPOUNDS. 381 



body twitches in response to pinching foot, even when the foot is no longer with- 

 drawn ; death within a minute with larger dose." These symptoms, with the 

 exception of the rapid death, have been present in all my experiments with effective 

 doses of tetra-ethyl-ammonium chloride, but only on few occasions have I seen slight 

 and transient fibrillary tremors in frogs after the injection of tetra-methyl-ammonium 

 chloride. Tremors are, however, mentioned as occurring before the paralysis by 

 Dufaux* and by Iodlbauer,! but they were not seen, although looked for, in the 

 experiments of Santesson and Koraen,| and are not referred to by Tillie.§ In 

 my experiments with tetra-methyl-ammonium chloride the symptoms produced by 

 all doses from 0'006 mg. to 5 mg. per gramme weight of frog have been typically 

 paralytic. And by injecting tetra-methyl-ammonium chloride previously or sub- 

 sequently to the administration of tetra-ethyl-ammonium chloride I have prevented 

 or annulled the contractions normally produced by the injection of the latter 

 substance. Even if one-tenth the amount of the tetra-methyl salt be injected 

 simultaneously with the tetra-ethyl compound, a notable limitation of the duration 

 of the time the fibrillary contractions continue is seen. As will be shown later, the 

 tremors produced by tetra-ethyl-ammonium chloride have their seat in the mechanism 

 associated with the myo-neural junction, and it is possible that the different results 

 obtained by different workers may have their explanation in the differences in this 

 mechanism. To this point I hope to return in a later communication. I have, 

 however, injected frogs at different times of the year and under different conditions 

 with tetra-methyl-ammonium chloride without producing tremors. Nevertheless, 

 fibrillary contractions may be produced for a brief period by applying small drops of 

 a solution of tetra-methyl-ammonium chloride to an exposed muscle, and these 

 commonly occur when an isolated muscle of a winter frog, but rarely when that of a 

 summer frog, is immersed in a solution. 



In view of the statement of Brunton and Cash || that tetra-methyl-ammonium 

 iodide and tetra-ethyl-ammonium iodide produce the same action, I have made a few 

 experiments on frogs with these substances. If certain slight differences due to the 

 iodide are ignored, the effects obtained are strictly comparable with those produced 

 by the corresponding chlorides. Tetra-methyl-ammonium iodide proved much more 

 powerful than tetra-ethyl-ammonium iodide, and it did not produce those powerful 

 irregular contractions and tremors which characterise the action of the latter 

 compound. Moreover, tetra-methyl-ammonium iodide, like the chloride, quickly 

 caused diastolic arrest of the heart, at least in doses of 0'15 mg. per gramme of frog 

 and above, an effect which was wanting in my experiments with tetra-ethyl- 

 ammonium iodide. 



On Rabbits. — The only experiments dealing with the effects of the tetra-ethyl- 

 ammonium compounds on mammals that I have been able to find are those of 



* Quoted by Santesson and Koraen, loc. cit. t Arch. Internat. de Pharmacod., vii. p. 188 [1900]. 



I Loc. cit, p. 220. § Loc. cit. || Loc. cit., p. 205. 



