PHARMACOLOGICAL ACTION OF TETRA-ALKYL-AMMONIUM COMPOUNDS. 485 



Effect on Circulation and Respiration. 



In the two previous communications # it was shown that tetra-methyl-ammonium 

 chloride in doses of one milligramme intravenously injected into anaesthetised rabbits 

 or cats caused temporary paralysis of the respiration and a fall of blood-pressure, 

 usually accompanied by diminution in the frequency of the heart beats, and that 

 tetra-ethyl-ammonium chloride in much larger doses failed to produce these effects. 

 It was only when very large doses of tetra-ethyl-ammonium chloride were injected 

 that some similarity in the action of the two substances was found to exist, such 

 doses producing a fall of blood-pressure, paralysis of the respiration, and depression 

 and even paralysis of the nerve-endings in the respiratory muscles, an effect which 

 I regard as the chief factor in the production of the respiratory paralysis caused by 

 tetra-methyl-ammonium chloride. 



The effects produced by the various methyl-ethyl-ammonium chlorides on the 

 circulation and respiration are broadly those which we might expect from their 

 chemical relationship to tetra-methyl- and tetra-ethyl-ammonium chlorides. It is 

 difficult to determine with accuracy the relative activity of the various compounds, 

 partly owing to differences in susceptibility of different animals and partly owing to 

 the fact that in the same animal later injections may be modified to some extent by 

 previous ones. But the following broad features are readily demonstrable : the 

 action of methyl-tri-ethyl-ammonium chloride is very similar to and slightly more 

 powerful than that of tetra-ethyl-ammonium chloride ; the action of tri-methyl-ethyl- 

 ammonium chloride is similar to but less powerful than that of tetra-methyl- 

 ammonium chloride ; di-methyl-di-ethyl-ammonium chloride holds an intermediate 

 position, but approaches in activity more closely to methyl-tri-ethyl-ammonium 

 chloride than to tri-methyl-ethyl-ammonium chloride. 



The following experiment is typical of those made. A cat, weight 3200 g., was 

 anaesthetised with chloroform, followed by ether ; the blood-pressure in the right 

 carotid artery and the respiration, by means of a phrenograph attached to a 

 tambour, were recorded ; the substances were injected into the right external jugular 

 vein. Three successive injections are shown in fig. 1. Prior to the first injection 

 shown, two injections of O'Ol g. and 0'02 g. respectively of methyl-tri-ethyl- 

 ammonium chloride were given. The smaller injection caused a slight fall in blood- 

 pressure (140 mm. Hg to 128 mm. Hg) and slight slowing and diminution in 

 frequency of the respiration (31 mm. to 22 mm. in height of tracing ; 10 to 9 respira- 

 tions in twenty seconds). The second injection caused a fall of blood-pressure from 

 142 mm. Hg to 134 mm. Hg, and of respiratory extent from 25 mm. to 17*5 mm. ; 

 the frequency was not appreciably altered. The first injection shown in the figure 

 was given ten minutes after the previous injection ; that shown in the second part 

 of the figure seven minutes later ; and the last injection twenty minutes later. It is 



* Trans. Roy. Soc. Edin., vol. 1., pt. i., p. 17 [1913]. Ibid., pt. ii., p. 379. 



