JOHN A. KOLMER 



II2I 



Furthermore, while ethylhydrocuprein and practically all cinchona derivatives 

 preserve a high degree of pneumococcidal activity in vitro in a menstruum of serum, 

 it is of special interest in relation to chemotherapy to note that the administration of 

 these compounds to human beings and the lower animals appreciably increases the 

 pneumococcidal activity of the blood. This fact, of course, possesses considerable 

 significance and lends great weight to the claims of Moore and Chesney and others 

 that the internal administration of 1.5 gm. of ethylhydrocuprein per day in divided 

 doses may be of benefit in the treatment of lobar pneumonia. 



MECHANISM OF THE BACTERIOSTATIC AND BACTERICIDAL ACTIVITY 

 OF THE CINCHONA DERIVATIVES 



Practically nothing has been yet discovered concerning the mechanism of the 

 bacteriostatic and bactericidal action of ethylhydrocuprein and other cinchona de- 

 rivatives for pneumococci and other organisms in vitro. Why these compounds possess 

 a high degree of selective activity for pneumococci is likewise unknown. Something 

 in their molecular structure establishes a special affinity for the protoplasm of these 



TABLE I 



organisms, but how they act in producing genesistasis or bacteriostasis and bacteri- 

 cidal efifects has not been elucidated. Very probably the mechanism is similar to that 

 concerned in the destructive effects of quinin for the malarial protozoa, but it may be 

 stated, however, that while optochin and ethylhydrocuprein are highly pneumo- 

 coccidal, they are regarded as inferior in the destruction of malarial parasites, which 

 indicates that they do not possess a pan-therapeutic activity but that their chemical 

 constitution renders them more especially destructive for the pneumococcus. 



TOXICITY OF CINCHONA DERIVATIVES 



Cohen, Heist, and myself found the lethal and maximum tolerated doses of 

 ethylhydrocuprein hydrochlorid and some of the salts of quinin approximately as 

 shown in Table I for rabbits and rats per kilogram of weight. 



By intraperitoneal injection the maximum tolerated doses have been from 0.150 

 to 0.200 gm. per kilo, by intrapleural injection from 0.020 to 0,040 gm. per kilo, and 

 by intracisternal or intraspinal injection about 0,003-0.005 gm. per kilo. 



As a general rule, mice stand slightly larger doses than rabbits. Individual experi- 

 ments also indicated that young rabbits were more resistant than older and heavier 

 animals, confirming the observations of Moore in this respect, 



A few years ago ethylhydrocuprein was rather widely employed in the treatment 



