176 Prof. J. N. Langley. On Nerve Endings and on [May 24, 



stimulating the nerve with the make or break of a galvanic current, or with 

 a single induction shock. The contraction, in fact, is of a peculiar kind, not 

 reproducible apparently by electrical stimulation of the nerve. 



As I have already said, it is well known that nicotine has a similar effect 

 to curari in so far as it prevents stimulation of a motor nerve from having 

 any effect upon the muscle. In the fowl the paralysis is produced by 10 to 

 15 milligrammes of nicotine. The stimulating effect of nicotine occurs 

 whether the amount given is sufficient to paralyse the motor nerves or no ; 

 amounts from about 0"5 milligramme upwards all cause contraction. 

 Moreover, after the nervous effect has been abolished by 10 to 15 milli- 

 grammes, a subsequent dose will still cause muscular contraction, and by 

 increasing the amount of successive doses contraction can be obtained 

 a considerable number of times in succession, though the effect diminishes 

 and at length ceases. This in itself is a curious fact,* for though it is 

 extremely common for a drug to stimulate first and then paralyse, the 

 recognised action of such drugs is to cease to stimulate after the paralysis has 

 been produced. 



The hypothesis which first suggests itself to account for this fact is that 

 nicotine acts in different ways upon two different parts of the neuro- 

 muscular mechanism, paralysing the nerve endings on the one hand, and 

 stimulating the muscle on the other. 



It is clear that this view would be confirmed if curari had no effect upon 

 the contraction caused by nicotine, for, as we have seen, curari is held to have 

 an action on nerve endings but not upon muscle. But experiment shows 

 that curari has a marked antagonising action on the contraction produced by 

 nicotine ; a sufficient dose of curari annuls the contraction produced by a 

 small amount of nicotine and diminishes that caused by a large amount. 

 The two poisons as regards muscular contraction are mutually antagonistic, 

 though nicotine is the more powerful. This point is of fundamental 

 importance, and I give the graphic records taken from one experiment in 

 illustration of it. 



Fig. 4 shows the contraction caused in a gastrocnemius muscle of the 

 fowlf by 4 milligrammes of nicotine. Whilst the contraction was at its 

 height, 50 milligrammes of curari were given. This it will be seen abolished 

 or nearly abolished the contraction. 



* Some other alkaloids have a similar action ; thus pilocarpin causes secretion, and 

 slows the heart after it has paralysed the post-ganglionic nerves. 



t The fowl was anaesthetised by morphia and A.C.E. mixture. The sciatic nerve was 

 cut. The lever attached to the gastrocnemius tendon was weighted with 40 grammes. 

 For other details of method, cf. ' Journ. of Physiol.,' vol. 33, pp. 381, 382, 1905. 



