LOCAL ANESTHETICS 345 



curiously enough, casually referred to by Niemann 1 which has 

 played so large a part in the determination of the constitution 

 of cocaine, and even in the preparation of the first synthetic 

 substitutes for cocaine. 



The earliest constitutional formula for cocaine was based 

 upon the formula for tropine suggested by Ladenburg. 2 

 Some years later this tropine formula was shown by Merling 3 

 to be insufficient to explain its reactions, and it was not until 

 1897-98 that the formulae of tropine and ecgonine was estab- 

 lished by Willstatter. 4 According to him these bases contain 

 a N.methyl-pyrrolidine and a N.methyl-piperidine ring united 

 to form a cyclo-heptane nucleus, which he termed tropan. 

 Ecgonine is the /S.carboxylic acid of tropine, and when methy- 

 lated and benzoylated yields cocaine. 



CH . COOCH 3 



I I 



N.CH 3 CH.O.COC 6 H 5 



Cocaine 



Pari passu with the investigations on the chemical con- 

 stitution of cocaine, a large number of derivatives of cocaine 

 were tested physiologically. Most of these were found to be 

 inactive or only slightly active as local anaesthetics ; a few 

 appeared to be more powerful than cocaine, but as they were 

 also more irritant they could not be used as substitutes for 

 this substance. Two noteworthy views, however, resulted 

 from some of these investigations. Filehne 5 came to the 

 conclusion that the benzoyl radical was the most important 

 factor in a local anaesthetic ; whereas it would appear from the 



1 Liebig's Annalen, cxiv. p. 216 (1860). 



2 Ber. d. deut. chem. Oes., xv. p. 1031 (1882) ; xx. p. 1647 (1887). 



3 Ber. d. deut. chem. Oes., xxiv. p. 3108 (1891). 



Ber. d. deut. chem. Oes., xxx. p. 2679 (1897) ; xxxL pp. 1202, 1534, 2498, 2655 

 (1898). 



5 Berlin, klin. Woch., 1887, p. 107. 



2 x 



