514 PROFESSOR C. R. MARSHALL ON THE 



The tremors which occur after the administration of tetra-alkyl-ammonium com- 

 pounds to frogs are probably due to an action on the same structures as those 

 involved in the paralysis. As regards nicotine, Langley is inclined to believe that 

 the tremors are an independent effect, and are due to an attachment of the nicotine 

 to the protoplasmic molecule through different receptor groups to those concerned in 

 the paralysis. He finds * that the antagonism of the fibrillary twitchings and of the 

 tonic contraction by curare follows different laws, the twitchings being abolished by 

 a definite percentage of curare through a considerable range of variation in the 

 concentration of the nicotine, while the early contracture of nicotine is abolished 

 only when the percentage of curare to that of nicotine is not less than a certain 

 definite one. This view of the independence of the tremors and paralysis receives 

 some measure of support from the facts that in some of my experiments the tremors 

 have continued after the animal has become completely paralysed, as shown by 

 stimulation of the sciatic nerves ; that in the case of the two substances, methyl-tri- 

 ethyl-ammonium chloride and tetra-ethyl-ammonium chloride, which show relatively 

 slight differences in paralysing power, the tremors are much more marked after tetra- 

 ethyl-ammonium chloride than after methyl-tri-ethyl-ammonium chloride ; and that 

 the calcium-ion appears to have greater influence in antagonising the twitches of 

 tetra-ethyl-ammonium chloride than in preventing the contracture produced by 

 tetra-methyl-ammonium chloride. 



Generally, however, the tremors gradually diminished with the increasing paralysis, 

 and disappeared before complete paralysis set in. The differences in the two sub- 

 stances mentioned are also much less marked when they are locally applied to 

 muscles ; and, as mentioned previously, the intimate association of the tremors with 

 the " nerve-endings" is shown by the fact that they may only occur during stimula- 

 tion of a nerve. When the whole series investigated is broadly considered, the 

 production of tremors seems to vary inversely with the power of the substance to 

 induce paralysis. The contracture produced, on the other hand, varies directly with 

 their paralysing power, and this effect and the tremors are prevented by previous 

 treatment with curarine. Owing to the somewhat variable reactivity of the muscles 

 of different frogs to these substances, it would be necessary to make a large number 

 of quantitative experiments to determine the dependence or independence of these 

 several effects ; but, so far as my observations have gone, they have led me to the 

 view that the tremors, contracture, and paralysis are, in the case of these tetra-alkyl 

 compounds, connected and due to a similar action upon the same structure. 



In the first paper of this series, which dealt mainly with the action of tetra- 

 methyl-ammonium chloride on the respiration, it was shown that the chief cause of 

 the temporary respiratory paralysis produced by this substance was a depression of 

 the myo-neural junction in the respiratory muscles. In the present paper it has been 

 shown that the various methyl-ethyl-ammonium compounds investigated produce 



* Joum. of Physiol., xlviii. p. 89 [1914]. 



