344 ON THE TOXICITY OF 



use of cocaine as a local anaesthetic ; but the suggestion was 

 not immediately adopted. It was not until Roller * showed, 

 four years later, that instillation of a cocaine solution into the 

 eye induced sufficient anaesthesia of the cornea to enable 

 operations on the eye to be painlessly performed, that the drug 

 came into general use as a local anaesthetic. Unfortunately 

 in not a few cases its use led to serious consequences. 2 Alarm- 

 ing symptoms and some deaths were ascribed to it ; and this, 

 coupled with the facts that in some cases it also produced 

 undesirable local effects, that it was expensive, and that its 

 aqueous solutions did not keep well and decomposed on 

 prolonged boiling, 3 thus precluding what was regarded as 

 efficient sterilisation, led to the desire for a more stable and 

 less toxic substitute. With one exception (tropacocaine) no 

 substitute of enduring value, however, was found until the 

 chemical constitution of cocaine had, to a large extent, been 

 determined. 



In 1862, two years after the isolation of cocaine, Lossen 4 

 showed that it was methyl-benzoyl-ecgonine ; and no further 

 advance in its chemistry seems to have been made until 

 after Keller's demonstration of its value as a local anaesthetic. 

 Then the work was actively pursued, especially by Einhorn 5 

 and his pupils. In the course of his investigations Einhorn 

 showed that anhydroecgonine could be decomposed into 

 tropidine and carbon dioxide 6 ; and he thus established the 

 close connection between atropine and cocaine a connection, 



1 Wien. med. Woch., 1884, pp. 1276, 1309. 



2 Falk (Therap. Monatsh., iv. p. 511 (1890)) collected 176 cases of acute cocaine 

 intoxication, of which ten were fatal, during the first six years of its use. 



3 Paul (Pharmae. Journ., 3 ser., xvi. p. 325 (1885) ). He was apparently of opinion 

 that benzoyl-ecgonine was possibly formed. This was proved to be the case by Einhorn 

 (Ber. A. deut. chem. Ges., xxi. p. 47 (1888) ). 



4 Liebig's Annalen, cxxxiii. p. 351 (1865). 



6 Ber. d. deut. chem. Gee., xx. p. 1221 (1887); xxi. pp. 47, 3029, 3441 (1888); xxii. 

 pp. 399, 1362, 1495 (1889); xxiii. pp. 468,979, 1338, 2889 (1890); xxvi. pp.324, 1482. 

 (1893) ; xxvii. pp. 1523, 1874, 1880, 2439 (1894). 



Ber. d. dent. chem. Ges., xxi. p. 3029 (1888). 



