CHEMICAL CONSTITUTION AND PHARMACOLOGICAL ACTION 439 



VIII. 



What practical conclusions can be drawn from these considera- 

 tions? We see that drugs, such as the majority of narcotics in 

 fact the large number of neurotropic and lipotropic substances be- 

 come localized through a shaking-out process. It follows from what 

 has already been said that only such substances can be anchored at any 

 particular part of the organism which fit into the molecule of the 

 recipient combination as a piece of mosaic fits into a certain pat- 

 tern. Such configurations, however, are not confined to a single 

 substance, but usually include a large group of related substances. 

 In this connection the investigations which Einhorn l and I made 

 concerning the action of cocaine are most important. 



Cocaine is a derivative of ecgonin, whose molecule contains two 

 groups differing in function: a hydroxyl group, which combines with 

 acid radicals, and a carboxyl group, which forms esters with alcohol 

 radicals. All derivatives of ecgonin in which both groups are thus 

 occupied represent bodies of the cocaine series. Thus in the cocaine 

 ordinarily used in medicine the acid radical is that of benzoic acid, 

 the ester former is a methyl group. By means of the methods of 

 modern chemistry it has been possible to introduce the greatest variety 

 of radicals into ecgonin, leading to the formation of a large number 

 of homologous substances. It was soon found that the substitution 

 of other alcohol radicals, such as ethyl, propyl, etc., for the methyl 

 radical did not cause the least change in the physiological effects 

 of the cocaine, as Falk proved. On the other hand, the acid radical 

 is of prime importance for the anesthetic action of the cocaine. Pouls- 

 son, Liebreich, and myself studied the various cocaines with other 

 acid radicals (cinnamyl cocaine, phenacetyl cocaine, valeryl cocaine, 

 phthalyl cocaine) and found only one, the phenylacetic acid derivative, 

 which possessed even feeble anaesthetic properties. As a result of 

 these toxicological experiences one could have assumed that this 

 benzoyl cocaine was in every way unlike all other acid derivatives. 

 But this is not the case, for I was able to show that so far as another 

 toxic action is concerned all of the various cocaines show the same 



1 Einhorn is one of the best authorities on alkaloids known to me. The 

 studies referred to, appear in the Deutsche med. Wochensch. 1890, No. 32, and in 

 Berichte der deutschen chem. Gesellschaft 1894, Vol. 27, page 1870. 



