PHARMACOLOGICAL ACTION OF TETRA-ALKYL- AMMONIUM COMPOUNDS. 487 



seen that the injection of 50 mg. of methyl-tri-ethyl-ammonium chloride produced 

 little effect. There is no distinct fall of blood-pressure and no distinct slowing of the 

 heart ; the respirations are diminished in extent, but the rate is uninfluenced. (It is 

 evident from the effects produced by smaller doses previously administered, that if 

 this quantity had been given at first a greater effect would have been produced in 

 this animal, but the comparison with the subsequent injections would have been there- 

 by to some extent invalidated.) The next injection of 27 mg. of di-methyl-di-ethyl- 

 ammonium chloride caused, as seen in the middle portion of the figure, a slight fall 

 of blood-pressure and a marked diminution in the extent of the respirations. The 

 respiration was not completely paralysed ; but, owing to a rapid fall of blood-pressure 

 which occurred, the commencement of which is shown in the figure, normal respira- 

 tion did not re-establish itself, and artificial respiration for a time became necessary. 

 The third portion of the figure shows the effect of injecting 9 mg. of tri-methyl-ethyl- 

 ammonium chloride. Some fall of blood-pressure, without obvious slowing of the 

 frequency of the heart, and rapid paralysis of the respiration followed. When the 

 blood-pressure had reached a low point artificial respiration was performed and 

 spontaneous breathing obtained, but the blood-pressure again fell rapidly, the 

 breathing ceased, and the animal succumbed. 



In rabbits, similar but somewhat greater effects were seen ; but neither in these 

 animals nor in cats was any distinct slowing of the heart's frequency observed such 

 as occurs after the injection of tetra-methyl-ammonium chloride. 



The only noteworthy variations from the action described were a temporary 

 increase in respiratory activity preceding the depression and a transient rise of blood- 

 pressure preceding the fall. The latter was only met with after the administration 

 of di-methyl-di-ethyl-ammonium chloride, and only in one animal (fig. 2). As will be 

 seen from the figure, the rise became greater with increase of dose. The action, 

 however, is probably not peculiar to this methyl-ethyl-compound, but is due to 

 certain undetermined conditions associated with particular animals or particular 

 states, and is not improbably connected with a refractory condition towards 

 anaesthetics. Tetra-methyl-ammonium chloride causes a rise of blood-pressure in 

 non-anaesthetised decerebrate animals, and occasionally it induces a small and 

 transient preliminary rise before the fall of blood-pressure in anaesthetised animals. 

 As the fall of blood-pressure was found to be largely peripheral in origin, the rise of 

 blood-pressure was attributed to an effect on the vaso-motor centre ; and the associa- 

 tion of increased respiratory activity concurrent with the rise of blood-pressure in 

 the tracing of di-methyl-di-ethyl-ammonium chloride shown, would also seem to 

 point to a central action. The diminished parallelism between the two effects seen 

 in the third portion of the figure may be due to depression of the nerve-endings in 

 the respiratory muscles and consequent interference with respiratory activity. The 

 appearance of the tracing, however, is also suggestive of a vascular effect of periph- 

 eral origin, and that such an action is not improbable is further suggested by 



