PHARMACOLOGICAL ACTION OF TETRA-ALKYL-AMMONIUM COMPOUNDS. 23 



Similarly, when the injection of tetra-methyl-ammonium chloride was made during 

 stimulation of the sciatic nerve, the fall of the muscle lever was gradual, and it did not 

 reach the abscissa before the respiration had recovered from its paralysis. The same 

 want of synchronism between the respiratory paralysis and the paralysis of the hind 

 limbs occurred after the injection of protocatechyl-tropeine, and led me to minimise the 

 peripheral origin of the respiratory paralysis. 



The effect of tetra-methyl-ammonium chloride on the terminations of the phrenic 

 nerve was determined in a number of instances, and found to be similar to that on the 

 nerves of the fore limbs. It will be referred to in considering the action of this 

 substance on the respiration. 



Effect on Decerebrate Animals. — After division of the brain through the quadrate 

 bodies and crura and delay for half to three-quarters of an hour after cessation of the 

 ansesthetic to allow of its excretion, the intravenous injection of tetra-methyl-ammonium 

 chloride produces in cats, less commonly in rabbits, immediate short clonic convulsions 

 (fig. 4). These convulsions may terminate in death. If not, the convulsions cease or 

 almost cease, and more or less paralysis of the motor nerve-endings may be demonstrated. 

 Even if convulsions do not occur, increased excitability can be shown to be present for 

 a few seconds after the injection by blowing on the animal. The reflex response to 

 this form of excitation is markedly increased immediately after the injection, and is 

 still present when the respiration has ceased (fig. 5). It quickly diminishes, however, 

 and a few seconds later no response can be elicited. The slight normal response returns 

 with or soon after the recommencement of the breathing, but no distinct increased 

 excitability occurred in the experiments in which this form of stimulation was tried 

 until another injection was made. Occasionally slight convulsive movements were 

 noticed in ansesthetised animals after a second or later injection. 



Most observers who have investigated the general effects of tetra-methyl-ammonium 

 compounds on mammals mention convulsions as a prominent symptom. Brunton and 

 Cash,* for example, state that after the injection hypodermically of 0*2 g. tetra-methyl- 

 ammonium iodide to a rat, the animal was affected at once with powerful convulsions ; 

 and similar results with much smaller doses of the chloride on mice and guinea-pigs 

 were observed by IoDLBAUER.f 



The seat of origin of the convulsions has not been determined. The simple response 

 to external stimulation (fig. 5) points to the spinal cord being involved ; but as the 

 convulsions exhibit a similar form to those produced by drugs acting on the basal 

 ganglia, it is probable that these structures are also affected, and as such drugs also act 

 on the motor areas of the cerebrum, these centres may be influenced as well. 



Effect on Frogs. — In the frog convulsions are not produced by the injection of 

 tetra-methyl-ammonium chloride into a lymph sac. The predominant symptom in 

 these animals is muscular paresis or paralysis. After a minimal paralytic dose the 

 respiratory movements cease within two minutes, and a minute later the animal is 



* Loc. cit., p. 207. + Loc. cit., p. 190. 



