PHARMACOLOGICAL ACTION OF TETRA-ALKYL-AMMONITJM COMPOUNDS. 393 



the cut cords of the brachial plexus with the secondary coil at 35 cm. gave a good 

 and constant contraction of the corresponding limb. Two minutes after an injection 

 of O'Oll g. per kg. body-weight into the external jugular vein, the same strength of 

 stimulus carried the writing lever off the drum, and the secondary coil had to be 

 placed at 40 cm. to produce the same curve as was previously obtained with the coil 

 at 35 cm. The effect of the next injection of 0'023 g. per kg. body-weight is shown 

 in fig. 3. Again the writing lever was carried off the paper by stimulating the 

 nerve with the same strength of stimulus (secondary coil at 41 cm.) as that used 

 previous to the injection. Even more pronounced increased susceptibility was 

 obtained in other experiments. 



Before the onset of this increased irritability small irregular twitchings of the 

 limb may develop. In the experiment referred to they occurred twenty to thirty 

 seconds before a notable increase in the irritability of the nerve was observed, but 

 were not a marked feature. Their commencement after the second injection is shown 

 towards the end of fig. 3. Later they became very marked, and were almost limited 

 to the time of stimulation of the nerve (fig. 4). This figure further shows that the 

 injection of a second dose of 0*023 g. per kg. body-weight does not prevent their 

 occurrence, although the irritability of the nerve, as shown by diminished contraction 

 of the limb, is temporarily lessened. On rabbits similar results were obtained. 



To this increased irritability of the nerve-endings the results obtained by 

 Rothberger * on curarised animals are in all probability due. He found that in 

 curarised cats the subcutaneous injection of tetra-ethyl-ammonium iodide was followed 

 in ten to twenty minutes by the reappearance of irritability of the sciatic nerves, 

 and later by spontaneous breathing. He came to the conclusion that undoubted 

 antagonism exists between tetra-ethyl-ammonium iodide and curare ; but as four of 

 his eight experiments were negative, the antagonism would appear to be relatively 

 slight and physiological in nature. 



Action on the Circulation and Respiration. 



In contradistinction to tetra-methyl-ammonium chloride, tetra-ethyl-ammonium 

 chloride exerts no distinctive action on the circulation. Jordan,! Tillie,| and 

 Jacobj and Hagenberg § state that it has no muscarin-like effect on the heart of frogs. 

 Jacobj and Hagenberg observed slowing of the heart after the administration of 0'5 

 to 07 mg. per gramme of frog, which was uninfluenced by atropine. Brunton and 

 Cash || noted diastolic standstill of the heart in frogs, and Santesson and Koraen 1 

 early cessation of the heart's action. In my own experiments on frogs the heart was 

 relatively little affected. In most cases it was beating well when the animal was 

 pithed. In one instance cessation of the ventricle in systole occurred ; and in the 

 few other cases in which cessation of the heart was observed after the administration 



* Loc. cit. t Loc. cit. I Loc. cit. 



§ Loc. cit., p. 58. || Loc. cit., p. 205. IT Loc. cit., p. 226. 



