PHARMACOLOGICAL ACTION OF TETRA-ALKYL-AMMONIUM COMPOUNDS. 39 



stimulation of the vagal endings in the heart, since it is unaffected by division of the 

 vagi and is abolished by the injection of sufficient atropine to paralyse these endings. 

 After paralysing the vagal endings by means of atropine, the injection of 1 mg. tetra- 

 methyl-ammonium chloride still causes a fall of blood-pressure, but the fall is more 

 gradual and is usually much less in extent that in non-atropinised animals. Otherwise 

 it runs a similar course. In cats after minimal doses the fall of blood-pressure and of 

 the frequency of the heart is usually less than in rabbits, but otherwise the effects 

 produced are the same. 



After larger doses the fall of blood-pressure is more rapid, more marked, and more 

 prolonged, and unless the respiration becomes efficient or artificial respiration is per- 

 formed, no recovery follows. In some cases even when spontaneous breathing has 

 recommenced or artificial respiration has been performed, the blood-pressure showed no 

 recovery or rose but slightly. In these the blood-pressure remained at a very low 

 level and the animal eventually succumbed. 



In decerebrate animals a fall of blood-pressure with slowing of the heart also 

 occurs (figs. 7 and 8), but is almost invariably preceded by a slight transient rise, also 

 associated with a diminution of the heart's frequency. With the fall of blood-pressure 

 the heart for a short period often becomes very slow. The vagal endings are also more 

 sensitive to stimulation than normally — a stimulus which before the injection produced 

 no effect causing after the injection a marked vagal action. The fall of blood-pressure 

 is succeeded by a rise, often considerably above the normal height, which is soon 

 followed by a fall below normal, the rise and fall occupying about twenty seconds. 

 After a varying interval gradual recovery occurs as in anassthetised animals. When 

 atropine has been given previously, there is usually little or no preliminary fall of 

 blood-pressure after the injection of small doses of tetra-methyl-ammonium chloride, 

 and after a short interval a considerable rise occurs, which is maintained for about 

 twenty seconds, and is followed by a fall to normal or a little below normal (fig. 5). 

 Iodlbauer # also observed a rise of blood-pressure in non-anaesthetised animals after 

 atropine had been given, but this was only followed by a fall below normal when large 

 doses of tetra-methyl-ammonium chloride were injected. 



The effect of tetra-methyl-ammonium chloride on the circulation is somewhat 

 complex. Iodlbauer, as a consequence of the experiment just mentioned, concludes 

 that it causes a marked stimulation of the vaso-motor centre, and, since he obtained 

 less slowing of the heart's frequency after than before division of the vagi, that it also 

 stimulates the cardio-inhibitory centre. The variable effects he obtained on the blood- 

 pressure he explains by stating that sometimes stimulation of the vagal mechanism, 

 sometimes stimulation of the vaso-motor centres, is predominant. The fall of blood- 

 pressure, apart from that caused by stimulation of the vagus, he believes is due to 

 paralysis of the vaso-motor centres. In my own experiments the stimulation of the 

 cardio-inhibitory centres was relatively slight ; after division of the vagi in decerebrate 



* hoc. cit., p. 196. 



