440 COLLECTED STUDIES IN IMMUNITY. 



behavior, namely, in mice they all produce a peculiar foam-like degen- 

 eration of the liver-cells which I have observed only in substances 

 belonging to this series. From this it follows that all bodies of the 

 cocaine series are alike so far as the liver is concerned. Considering 

 that the substances which precipitate and dissolve these bodies are 

 the same and that the liver findings are identical, we may perhaps 

 assume that all cocaines are taken up by the liver in the same way 

 and therefore probably also by the other parenchyma. And since 

 the benzoyl derivative is the only one which possesses anaesthetic 

 action we shall have to assume that the rest of the molecule is only 

 the carrier which brings the benzoic acid radical to the proper place. 

 (The anaesthesiophore character of this group had already been made 

 very probable by the earlier investgations of Filehne.) Let us go 

 back to our illustration of the mosaic in order to get this idea clearly 

 before us. In order for a piece to help complete a given figure it is 

 first necessary that it possess a particular form, but in order that the 

 pattern be really completed the piece must also possess certain material 

 properties, such as hardness, color, lustre, etc. It will be one of the 

 problems of the future to extend our knowledge concerning the active 

 toxophore groups. 



The first fundamental experiments in this direction were made 

 by Ladenburg, who showed that the two substances obtained on 

 splitting atropin, namely, tropin and tropic acid, could readily be 

 recombined and the atropin molecule thus be reconstructed. As a 

 result of this demonstration that atropin represents an acid ester 

 of tropin it was possible to produce a number of homologous combina- 

 tions, Ladenburg's "tropeins," e.g., benzyltropein, salicyltropein, 

 phenylglycoltropein (homa tropin). A comparative study of the these 

 substances showed that for mydriatic purposes aromatic oxyacids 

 were the most favorable and especially those in which the hydroxyl 

 is in aliphatic combination, as in tropic acid and phenylglycolic acid. 



In cocaine, Einhorn and I attempted to determine the function 

 of the benzoyl group by introducing various side-chains. It was 

 found that the introduction of a nitro group in the meta position had 

 a marked influence on the anaesthetizing property of cocaine without 

 preventing the injurious action on parenchyma described above. The 

 introduction of a hydroxyl group in the same place acted still more 

 strongly in this direction, for the anaesthetizing property had dis- 

 appeared, the toxic action on the liver decreased. Meta-amido cocaine 

 was entirely inert. 



