CHEMICAL CONSTITUTION AND PHARMACOLOGICAL ACTION. 425 



V. 



The question now arises as to how we conceive this selection of 

 the tissues to occur. It is very probable a priori that we are dealing 

 with chemical affinities in the widest meaning of the term. We must, 

 however, discuss in detail the nature of these affinities. In this, 

 I must emphasize, we are dealing primarily with substances which, 

 like the various natural and artificial drugs, are foreign to the body, 

 not with foodstuffs capable of assimilation. The latter will be 

 treated by themselves subsequently. 



The simplest case is that in which the organism is injected with 

 indifferent substances, neither acid nor basic in character, to which, 

 corresponding to their constitution, we can ascribe no great chemical 

 affinities, but which nevertheless exert marked and often highly 

 toxic effects. In this category belong especially the various hydro- 

 carbons, e.g. toluol, benzol; a number of ketones, such as acetophe- 

 non ; many sulfones, which are characterized by their chemical in- 

 difference; also various kinds of ethers, alcohols, and a large number 

 of other narcotics. The best opinion seems to be that in these 

 cases no direct chemical affinities come into play on the part of the 

 organism, and that the molecule is always present in the tissue 

 constituents unchanged and chemically uncombined. That is to 

 say, the phenomenon is one of contact action. In spite of this it 

 can readily be shown that all these compounds possess a typical 

 localization in the tissues, the cause of which we shall soon discuss. 



First, however, I should like to say a few words concerning the 

 historical side of this question. The idea that chemical substances 

 can act solely through contact was first affirmed many years ago, 

 thus by Buchheim in 1859, Schmiedeberg in 1883, Harnack in 1883, 

 and by Geppert. The latter 's investigations may be found in the 

 Zeitschrift fur klin. Medicin, Vol. XV, and deal with the nature of 

 prussic-acid poisoning. He showed that in this highly interesting 

 case the hydrocyanic acid acts as such. He explained the result of 

 the toxic action in the following manner: 



" We know that chemical processes are retarded simply through the 

 presence of minimal amounts of prussic acid. Thus iodic acid does 

 not yield up its oxygen to formic acid under conditions otherwise 

 favorable if even a minimal amount of prussic acid is present. It 

 is quite natural, I suppose, that in the poisoned organism, highly 



