512 BIOLOGY OF PNEUMOCOCCUS 



Cinchona Derivatives 



EFFECT OF THE VARIOUS QUININE DERIVATIVES ON PNEUMOCOCCI 



Quite different from the agents already described in their action 

 on pneumococci are certain products prepared from the alkaloid, 

 cinchona. In the first experiments reported by Morgenroth and 

 Levy (1911), 9267 quinine was found to be valueless in sparing 

 from infection mice inoculated with a fatal dose of pneumococci. 

 However, when the related substance, hydroquinine (methylhydro- 

 cupreine) was used, the pneumococcidal effect was marked and a 

 yet more pronounced action was observed when the next higher 

 homologue, ethylhydrocupreine (optochin) was employed. The two 

 substances in the form of aqueous solutions of their respective sul- 

 fates and hydrochlorides, when injected into mice at the time of 

 inoculation or during the course of a virulent pneumococcal infec- 

 tion, saved a significant number of the test animals. Ethylhydro- 

 cupreine sulfate was less toxic and more potent in protective and 

 curative action than was the hydrochloride of methylhydrocu- 

 preine. Another homologous derivative possessing active pneumo- 

 coccidal properties, as determined by Morgenroth and Bumcke, 921 

 was isopropylhydrocupreine. Vuzine, described by Morgenroth, 920 

 is also an active homologue, but its action is influenced by varia- 

 tions in the susceptibility of different pneumococcal strains. 



A disadvantage of the watery solutions of these alkaloidal salts 

 was their rapid absorption and excretion — a disadvantage over- 

 come by Morgenroth and Kaufmann, 922 " 5 as well as by Gutmann, 582 

 by dissolving the optochin base in oil. The toxicity of this type of 

 compound, according to Morgenroth and Kaufmann, could be low- 

 ered by substituting the salicylic ester of optochin, and it was 

 found that of the homologues of hydroquinine, optochin was the 

 most active in germicidal effect on pneumococci. 



The sterilizing action of optochin on pneumococci in vitro was 

 demonstrated by Wright, Morgan, Colebrook, and Dodgson, 15434 a 

 result corroborated by Schiemann and Ishiwara. 1230 Optochin in 



