PHARMACOLOGICAL ACTION OF TETRA-ALKYL- AMMONIUM COMPOUNDS. 37 



fall being more gradual and the slowing of the heart's frequency much less marked 

 after the intra-arterial than after the intravenous injection. 



The paralysing action of this substance on the respiration would therefore seem not 

 to be due to an action on the respiratory centre. Nor is it due to an action on the 

 circulation or on the peripheral nervous mechanism within the lungs, since, as will be 

 shown later, it is much more transient than the circulatory action, and it is obtained 

 after section of both vagi or after the injection of sufficient atropine to paralyse the 

 vagal terminations. 



That tetra-methyl-ammonium chloride is not without action on the respiratory centre 

 is evident from the experiments on decerebrate animals. But instead of being 

 depressant to this centre, it is powerfully stimulant. And that the paralysis is not 

 due to exhaustion following stimulation is obvious from the fact that stimulation of 

 the respiration is usually present in decerebrate animals after the paralytic stage has 

 passed away. The larger doses of tetra-methyl-ammonium chloride which are some- 

 times necessary to paralyse the respiration of decerebrate animals, and the more rapid 

 recovery from the paralysis, also point to this conclusion. It has been mentioned that 

 strong or moderately strong electrical stimuli applied to nerves may still produce 

 contraction of the innervated muscles after doses of tetra-methyl-ammonium chloride 

 sufficient to paralyse the respiration, although moderately weak stimuli may no longer 

 do so, and there can be little doubt that a powerfully stimulated respiratory centre acts 

 in a similar manner, only more efficiently. In other words, the impulses from a 

 respiratory centre in this condition are able to overcome a greater degree of depression 

 in the peripheral structures, and hence the depression must be made more profound by 

 the injection of larger doses in order to obtain paralysis ; and as the stimulation continues 

 for a much longer time than the paralysis, the more rapid recovery may be similarly 

 explained. It is probable that the convulsant action noticed after toxic doses to normal 

 animals has a similar explanation. That the stimulation of the respiratory centre does 

 not occur in anaesthetised animals when the substance is administered intravenously is 

 due to the well-known fact that it is more difficult to stimulate this centre in anaesthetised 

 than in normal animals, and any slight stimulation which may be induced would, in 

 this case, be checked by the simultaneous paralysing action on the myo-neural junctions. 

 By the injection of small doses into the carotid artery of anaesthetised animals, slight 

 stimulation of the respiration, both increase in depth and in frequency, can be 

 demonstrated. 



Influence of the Vagus on the Respiratory Paralysis. — Anaesthetised animals in 

 which both vagi have been divided are more sensitive to the action of tetra-methyl- 

 ammonium chloride than animals with the vagi intact. Thus a dose which may 

 produce in an ordinary anaesthetised animal slight temporary depression without 

 cessation of the respiration will, after section of both vagi, cause complete temporary 

 paralysis ; or a dose sufficient to paralyse for a few seconds the respiration of an animal 

 with undivided vagi, may, after the vagi have been cut, produce permanent respiratory 



