1906.] 



Special Excitable Substances in Cells. 



181 



The mutual antagonism of nicotine and curari on muscle* can only 

 satisfactorily be explained by supposing that both combine with the same 

 radicle of the muscle, so that nicotine-muscle compounds and curari-muscle 

 compounds are formed. Which compound is formed depends upon the mass 

 of each poison present and the relative chemical affinities for the muscle 

 radicle. 



Since the formation of the nicotine-compound causes contraction, and that of 

 the curari-compound does not, it is obvious that the chemical re-arrangements 

 set up in the muscle molecule by the combination of one of its radicles are 

 different in the two cases. In fact, it seems probable that a special radicle is 

 necessary for the combination with a number of chemical bodies, and that 

 the compound formed leads to further change depending upon the nature of 

 the compound. 



Having then arrived at the conclusion that both nicotine and curari 

 combine with some substance in the muscle, we have to consider whether 

 there is any reason to suppose that they combine with some substance in the 

 nerve ending also. The only action that can be attributed to them is the 

 paralysing action. 



There is, unfortunately, no direct and conclusive evidence either one way or 

 the other. But as the ascertained action of the poisons on muscle is 

 sufficient to explain their paralysing action, it is unnecessary to resort to the 

 assumption of an additional effect on nerve endings. It is a common action of 

 drugs first to stimulate and then to paralyse, so that there is plenty of analogy 

 for the view that nicotine, after stimulating, paralyses the constituent of the 

 muscle on which it acts. 



Curari, as we have seen, decreases the irritability of the muscle to the 

 nicotine stimulus, and it is reasonable to suppose that it decreases also the 

 irritability of the muscle to stimuli arriving by the nerves. I conclude, then, 

 in terms of the theory given above, that the compounds which the poisons 

 form with the muscle are less irritable and conductive than the normal 

 muscle substance. 



The continuation of the stimulating effect of nicotine after nervous impulses 



* Pal (' Centralb. f. Physiol.,' 1900, p. 255) found that curari nerve-paralysis could be 

 more or less completely abolished by physostigmine. The matter was further worked out 

 by Eothberger ('Arch. f. d. ges. Physiol.,' vol. 137, p. 117, 1901), who also showed (ibid., 

 vol. 92, p. 398, 1902) that several substances, and amongst them nicotine, can, in proper 

 conditions, partly restore irritability to motor nerves paralysed by curari. In writing 

 my earlier account (op. cit. supra) I was unaware of Rothberger's observations. The 

 physiological antagonism in this case is very incomplete, a fact which is in harmony with 

 the theory of antagonism of poisons I gave some years ago (' Journ. of Physiol.,' vol. 1, 

 p. 367, 1878). 



