350 ON THE TOXICITY OF 



C 2 H 5 C.O.COC 6 H 5 C 2 H 5 C.O.COC 6 H 5 



/\ /\ 



2 C C 



H 3 C CH 2 . N(CH 3 ) 2 HC1 (CH 3 )2N.H 2 C CH 2 . N(CH 3 ) 2 HC1 



Stoyaine Alypine 



of the methyl group of this compound another local anaesthetic, 

 named alypine, was obtained. 1 



The toxicity of these various substances was determined 

 previous to their introduction into therapeutics, and in most 

 cases it was compared with and found to be less than that of 

 cocaine. During the last few years, mainly owing to the em- 

 ployment of these compounds to produce spinal anaesthesia, 

 the question of their relative toxicity has assumed greater 

 importance, and several and varied investigations have been 

 made with this end in view. Laewen 2 employed the sciatic 

 nerve of the frog, and compared the relative effects of cocaine, 

 novocaine, alypine, and stovaine. Taking into account the 

 degree and rapidity of recovery after the anaesthetic had been 

 replaced by Ringer's solution, the order of toxicity would 

 appear from his research to be stovaine, alypine, cocaine, 

 novocaine, the last being the least toxic. More recently, Le 

 Brocq 3 has determined the toxicity of various local anaes- 

 thetics on frogs, mice, and rabbits. Assuming the toxicity 

 of cocaine to be represented by TO, he concludes that the 

 toxicity of the other substances may be represented as follows : 

 alypine, 1-25; nirvanine, 0'714; stovaine, 0'625 ; tropaco- 

 caine, CK500 ; novocaine, O490 ; beta-eucaine lactate, O414. 



My own experiments were made previous to the publica- 

 tion of the last-mentioned paper, and the observations were 

 limited to the relative effects on the circulation and respiration, 

 as it is mainly through these systems that these drugs produce 

 their most serious ill-effects. As only a relative effect was 

 required, the whole of the experiments were made on etherised 

 rabbits. The blood-pressure was taken from the common 

 carotid artery, and the respiration was recorded by means of a 



1 Impena, Deut. med. Woch., 1905, ii. p. 1154. 



2 Arch.f. exp. Path. u. Pharmak., Ivi. p. 138 (1907). 



3 Brit. Med. Journ., 1909, i. p. 783. 



