36 PROFESSOR C. R. MARSHALL ON THE 



tion nearly twenty minutes elapsed after the paralysis of the respiration before 

 practically normal respiration was established, and it was some minutes later 

 before the diaphragm reacted to stimulation of the phrenic to the extent it did 

 previous to the injection. After the injection of double this dose, paralysis of the 

 muscles and respiration appears much more quickly, but three to four times the dose 

 mentioned is necessary to produce that rapid paralysis of the respiration which is seen 

 after tetra-methyl-ammonium chloride. Owing to the prolonged action of curarin on 

 the myo-neural junctions, a strict comparison with the paralysing action of tetra-methyl- 

 ammonium chloride on the respiration is not possible ; but it is interesting to note that 

 the type of the paralysis is the same in both cases and that after large doses of the 

 two substances the paralysing effect on the respiration is practically identical. In view 

 of the convulsant action of tetra-methyl-ammonium chloride, it is further of interest to 

 note that Tillie # observed weak convulsions, apparently on non-anaesthetised animals, 

 after the injection of 1 mg. to 2 mg. curarin prior to the appearance of complete 

 paralysis, and these were more marked when artificial respiration was performed 

 throughout the experiment. 



There still remains the question whether the cause of the respiratory paralysis is 

 wholly due to the paresis of the nerve endings in the respiratory muscles. As previously 

 mentioned, PoHL,t working with some quaternary papaverine derivatives, observed 

 this form of temporary expiratory paralysis with spontaneous recovery after intravenous 

 injections into rabbits. And yet he found that these substances had no paralysing 

 action on the motor nerve-endings of frogs. He came to the conclusion that the effect 

 on the respiration was due to an action on the respiratory centre, and he explained the 

 effect of tetra-methyl-ammonium chloride in the same way. But the only experiment 

 he appears to have made was one to controvert the view of Tappeiner, and in this he 

 divided the ophthalmic branches of the fifth cranial nerves, and still found that he 

 obtained the characteristic paralysis of the respiration after the intravenous injection of 

 this substance. Its action was not further investigated. 



In order to determine whether the paralysing action on the respiration produced by 

 tetra-methyl-ammonium chloride is partly central, two experiments in which the injec- 

 tions were made alternately into the carotid artery and the facial vein were performed 

 on anaesthetised rabbits. Although the concentration of tetra-methyl-ammonium 

 chloride reaching the respiratory centre after injection into the artery must have been 

 considerably greater than after injection into the vein, a larger dose was necessary to 

 induce respiratory paralysis. Thus the injection of 1 mg. into the carotid artery pro- 

 duced in both animals merely slight gradual diminution of depth and slowing of the 

 respiration, whereas this dose, when injected into the facial vein, caused almost complete 

 temporary paralysis. When double the dose injected into the vein was injected into 

 the artery, almost identical effects on the respiration were obtained from the two 

 injections. Some difference was noted in the initial effects on the blood-pressure, the 



* hoc, cit., ]>. 22. t Loc. cit. 



