1910.] Nicotine and other Pyndine Bases upon Muscle. 



343 



of nicotine to strychnine = 1 : 2'5 (nicotine w/lOOO + stryclinine 7i/400); 

 the nicotine effect was entirely replaced by the strychnine effect. In the 

 proportion N:S = 4:1 (nicotine »/1000 + strychnine «/4000) the nicotine 

 effect is not completely abolished. 



We have also tested mixtures of nicotine and aconitine. Taking a 

 mixture of nicotine ?i/1000 and aconitine ?«/40000 (N : A = 40 : 1), we found 

 that the nicotine effect was absolutely unaltered. With a mixture of 

 nicotine ?i/1000 and aconitine ?i/2000 the nicotine effect was abolished, 

 the record being what we should term a modified aconitine recoi-d. With 

 nicotine ?i/1000 and aconitine «/20000 the nicotine efiect was just visible, 

 while with nicotine ii/lOOO and aconitine ??/10000 the nicotine effect was 

 abolished. 



We also tested mixtures of nicotine and quinine. With a mixture of 

 nicotine ?i/1000 and quinine «/1000, we obtained a record indicative of 

 a subdivision, with a considerable predominance of the quinine over the 

 nicotine effect. In the proportion nicotine «/1000 : quinine ?i/ 5000 (= 5 : 1) 

 the nicotine effect was not abolished, but in the proportion nicotine 

 vi/1000 : quinine ?t/10000 (= 10 : 1), the nicotine effect is unaltered; that 

 is to say, the effect of 10 molecules of nicotine is not overcome by a molecule 

 of quinine, nor that of five molecules completely so, whereas one molecule of 

 nicotine is overpowered by one molecule of quinine. 



Thus in none of these cases could we regard nicotine as antagonised as by 

 curarine. The results were such as to indicate either a subdivision of the 

 muscle protein between two bases or the displacement of a weaker base by a 

 stronger. Whereas in the case of curarine we have a substance with little 

 toxic action on muscle itself, yet of which one molecule was sufficient to very 

 nearly abolish the effect of 160 molecules of nicotine, but it required 

 1 molecule of strychnine or quinine to overpower 1 molecule of nicotine ; and 

 1 molecule of the most powerful poison we have used, viz., aconitine, could 

 overpower at most 10 molecules of nicotine. 



Langley considers that both nicotine and curare combine with some sul)- 

 stance in the muscle itself, and that it is unnecessary to resort to the 

 assumption of an additional effect on nerve-endings ; he finds, indeed, that 

 the antagonism between these two poisons occurs in muscle of which the 

 nerves have completely degenerated. 



We find it difficult, in presence of the fact that curarine (which acts power- 

 fully on nerve-endings, feebly upon muscle) does very readily antagonise the 

 characteristic nicotine effect (the seat of which is now in question), to avoid 

 the conclusion that such nicotine effect takes place at the nerve-ending, and 

 is there antagonised by curarine. 



