512 PROFESSOR C. R. MARSHALL ON THE 



strength is applied after the contracture produced by a 0*3 per cent, tetra-methyl- 

 ammonium chloride solution has passed away, no immediate contracture is produced, 

 but the late contracture follows with normal intensity in due course. It has been 

 shown that such a strength of tetra-methyl-ammonium chloride, while exerting a 

 maximum effect on the myo-neural junction, has relatively little action on the 

 contractile tissue of the muscle itself, and these experiments consequently support 

 Langley's view that the second contracture is due to a direct action on the con- 

 tractile tissue. Further corroboration of this view was obtained from experiments 

 on the effect of rhythmical stimulation of muscles immersed in nicotine solutions. 

 Since the form of the immediate contracture produced by nicotine and by tetra- 

 methyl-ammonium chloride is the same, and as both are prevented by previous 

 treatment of the muscle with curarine, and as this portion of the nicotine action 

 can be replaced by a similar action of tetra-methyl-ammonium chloride, which 

 leaves the nerve-endings still irritable, it would seem that the action of the two 

 substances as regards this particular effect is upon the self-same structure. Langley 

 has shown in the case of nicotine that the effect is still obtained after degeneration 

 of the nerves and of the motor end plates ; and that the seat of action is distal to 

 the nerve-endings seems to follow from the marked contracture produced by tetra- 

 methyl-ammonium chloride after exhaustion of the nerve, illustrated in fig. 15. The 

 markedly diminished irritability of the sartorius muscle to direct stimulation, which 

 succeeds the contracture, and which does not seem to me to result from the previous 

 activity, also points, I think, to a more intimate connection of the substance or part 

 affected with the contractile substance proper than is usually associated with the 

 nerve terminations. Whether this substance is of the nature of Keith Lucas's ft 

 substance or is another substance distinct from the contractile substance of the 

 muscle cell is difficult to decide. The rapidity and independence of the early con- 

 tracture, as well as its distribution, strongly suggest an effect on such a substance as 

 the /3 substance ; but although Keith Lucas found * that this substance was paralysed 

 with much smaller doses or concentrations of curare than the contractile substance 

 of the muscle, he further found that the ft substance was still irritable after the 

 nerve-endings were paralysed. This is not, to my mind, a reason sufficient to exclude 

 the |8 substance as the seat of action of tetra-methyl-ammonium chloride, but further 

 work is necessary before any certain conclusion can be drawn. 



Langley's receptive substance I understand to be different from the /? substance. 

 He assumes that the mode of action of this class of drugs is essentially chemical in 

 nature and due to attachment of the drugs to the protoplasmic molecule of the 

 receptive substance by means of receptor groups. It does not seem to me necessary 

 to assume this manner of combination to explain the effects which have been 

 observed, nor does it help to an understanding of the phenomena. It is particularly 

 difficult to see how this theory can explain the difference in action between tetra- 



* Journ. of Physiol., xxxvi. pp. 122, 125 [1907]. 



