PHARMACOLOGICAL ACTION OF TETRA-ALKYL-AMMONIUM COMPOUNDS. 483 



minutes later. Fifty-five minutes, moving about ; tremors present. Sixty minutes, 

 recovered once but not twice from back position. Seventy minutes, still on back. 

 Twenty hours, moves sluggishly and shows slight tremors on probing ; otherwise 

 normal. 



Tetra-ethyl-ammonium Chloride. — The same dose given on the same occasion 

 produced similar symptoms to those last described, except that fibrillary tremors 

 were more marked. An injection of tetra-methyl-ammonium chloride was not made 

 on this occasion, but, as stated in a previous paper, paralysis, and very rarely slight 

 transient tremors, are produced by 0'006 mg. per gramme of frog. 



The relative activity of these substances is also seen in the following tables. 



Effect of O'l mg. per gramme body-weight. 



Tetra-methyl-ammonium chloride 

 Tri-methyl-ethyl-ammonium chloride 

 Di-methyl-di-ethyl-ammonium chloride 

 Methyl-tri-ethyl-ammonium chloride . 

 Tetra-ethyl-ammonium chloride 



Paralysis in two minutes. 

 Paralysis in five minutes. 

 Slight depression, no paralysis. 

 Sometimes few slight tremors. 

 Well-marked tremors. 



The minimal dose producing a degree of paresis sufficient to prevent the animal 

 turning over when placed upon the back was found to be as follows : — 



Minimal Dose inducing Paresis. 



Tetra-methyl-ammonium chloride . 

 Tri-methyl-ethyl-ammonium chloride 

 Di-methyl-di-ethyl-ammonium chloride 

 Methyl-tri-ethyl-ammonium chloride 

 Tetra-ethyl-ammonium chloride 



005 mg. per gramme hody- weight. 



o-oi „ 



013 „ 

 0-2 „ 

 0-2 „ 



The smallest doses necessary to produce a similar degree of paralysis, manifest 

 in the same way, in five and fifteen minutes respectively, is shown in the following 

 table. The figures refer to milligrammes per gramme body-weight of frog : — 



Doses inducing Paresis in Jive minutes and fifteen minutes. 



Tetra-methyl-ammonium chloride 

 Tri-methyl-ethyl-ammonium chloride 

 Di-methyl-di-ethyl-ammonium chloride 

 Methyl-tri-ethyl-ammonium chloride . 

 Tetra-ethyl-ammonium chloride 



In some experiments larger doses than those mentioned were administered without 

 producing paresis, or paresis within the stated time. The figures given indicate the 

 average relative activity of the various compounds as observed in a number of 

 experiments with varying doses. Considerable variation in the action of all the 

 substances was observed in different frogs and at different times. Small frogs were 

 more sensitive than large frogs in proportion to the body-weight ; and frogs tested 



5 



mins. 



15 mins. 



0-02 mg. 



per g. 



0006 mg. per g. 



0-06 „ 



,, 



0-015 „ „ 



0-5 „ 



» 



025 „ 



1-5 „ 



n 



05 „ „ 



10 „ 



" 



0-4 „ „ 



