170 SECTIONAL ADDRESSES. 



The specific action of organic arsenic compounds really begins with 

 pome observations of Thomas on the action of atoxyl on trypanosomes. 

 Ehrlich had previously discarded this substance because it was without 

 direct action on the protozoon, but later he observed, like Levaditi and 

 Mesnil, that in infected animals it had a more pronounced action than 

 that of any other substance up to then employed. Atoxyl was, however, 

 soon discarded as a curative remedy because it caused permanent and 

 complete blindness in some cases. Acetyl atoxyl, known as arsacetin, 

 which was at one time widely used, had no better fortune, and several 

 cases of permanent blindness resulted from its use. Ehrlich' s experiments 

 with Hata, in which innumerable arsenical compounds were employed, led 

 him to select salvarsan as the best : in this substance the nitrogen and 

 arsenic are in the meta position and not in the para as in atoxyl. This 

 substance as a treatment of syphilis and other spirochaetal infections 

 stands as firmly to-day as it did ten years ago ; it has one drawback, 

 it does not influence the condition of the patient if the central nervous 

 system is attacked. By introducing CHjOS.ONa in place of one of the 

 hydrogens in the amino group a soluble compound is produced which 

 has displaced the older salvarsan on account of its ease of administration ; 

 nevertheless this neo-salvarsan contains as much as 10 to 20 per cent, of 

 unknown impurities. Other substances like tetra-methyl hexamino- 

 arsino benzene (Arsalyte Giemsa) have been produced which are also very 

 efficient in spirochaetosis. 



It is well known now that none of these compounds act directly on the 

 parasite (Ehrlich, Levaditi, Mesnil, and others) like arsenious acid. 



NHj '\ > Ky> NH.CHjOS.ONa 



N.CHj.CONHj OH OH 



Atoxyl Tryparsamide Salvarsan 



(NHj in para position) (NH2 in para position) with solubilising group 



(NHj in meta position) 



It was at one time thought that the action of these arsenicals depended 

 on their solubility in lipoid substances and their subsequent oxidation to 

 arsenic in the ionic form : but after their administration to animals no 

 trace of oxide is found in the body. About 115 mgrms. of atoxyl per 

 kilo can be injected into mice, but only about 2 mgrs. per kilo of the 

 corresponding oxide for the maximal sub-lethal dose. It is probable that 

 the lipoid soluble and inert atoxyl in the pentavalent form is converted 

 into the trivalent form which destroys trypanosomes like arsenious acid. 

 Fourneau from a great number of experiments with different organic 

 arsenicals concludes that their varying constitution as regards the intro- 

 duction of different side-chains in the ring, and the varying positions of 

 these relatively to one another, is the factor which determines their 



