404 



Organic Oximides : their Pharmacology. 



[May 4, 



Acetone is almost innocuous to the frog's heart in all but very- 

 strong doses, when the only action is depressed systole with final 

 arrest in diastole. 



Seeing, therefore, the resemblance in action found to exist between 

 a ketoxime and an aldoxime, and also between isonitrosoacetone and 

 an aldoxime ; seeing, further, the resemblance in action between the 

 involved aldehydes and ketone, it must follow, as a corollary, that the 

 influence of the oxime group must in each case be the same. This 

 influence is that of a nitrite, as was also found to be the case in the 

 aromatic aldoximes. 



The only discrepancy arises in the actions of acetoxime and of iso- 

 nitrosoacetone on voluntary muscle. They both give rise, when pre- 

 sent in strong solution, to the development of some contracture, a 

 phenomenon which cannot be ascribed to acetone. 



During the course of this research it has been sought to explain 

 the nature of muscle contracture, and it has been determined that 

 the phenomenon is probably due to direct irritation of the nerve end 

 plates, the irritant in the case of these oximido-bodies being an 

 aldehyde, or, perhaps, more accurately, the OOH group. 



In support of this contention several facts may be here adduced. 



It is an active process associated with an increased formation of 

 heat. 



Tracings show the onset and decline of contracture to be in rela- 

 tionship with the shortening and lengthening of the latent period. 



The development of contracture is prevented by curare. 



A primary increase of irritability in the nervous path of muscle- 

 nerve preparations can be traced to the end plates. 



This irritability, better expressed as exalted conductivity of the 

 end plates, becomes more marked as the power of the aldehydes to 

 cause contracture increases. 



The decline of contracture is synchronous in its onset with the loss 

 of conductivity through the end plates. 



Experiments on the oxidation of acetoxime and isonitrosoacetone 

 have led to the detection of an aldehyde — -pyroracemic aldehyde, in 

 the case of acetoxime, and acetylformic aldehyde in the case of iso- 

 nitrosoacetone. This formation of aldehyde, should it take place in 

 the tissues, would then be a sufficient explanation for their giving rise 

 to contracture. On the other hand, it might be argued that the 

 oxime group, whilst in all other respects giving rise to actions 

 identical with those of nitrites, yet exerts a primary stimulant action 

 on nerve centres and on the muscle end plates. Such an action this 

 investigation has not disproved. 



