CHEMOTHERAPY 517 



vitro, it afforded practically no protection to mice against experi- 

 mental pneumococcal infection. 



Other experiments that serve to substantiate the claims of Mac- 

 lachlan and his colleagues are those of Butler, Nelson, Renfrew, 

 and Cretcher. 193 The authors tested cinchona alkaloids, their hy- 

 drogenated derivatives, and some artificially prepared homologues 

 and reported that hydroxyethylhydrocupreine was less toxic for 

 mice than optochin and was highly efficient in protecting the test 

 animals against pneumococcal infectio . In a second communica- 

 tion, Butler and Cretcher 192 stated that apocupreine hydrochloride 

 displayed fairly high pneumococcidal action in vitro, when com- 

 pared to other members of the cinchona group, was very low in 

 toxicity for mice, and possessed protective properties similar to 

 those of optochin and ethylapoquinine. 



Optochin and its allied compounds possess marked disadvan- 

 tages. The substances do not penetrate the infected lesions and, 

 therefore, do not affect the cocci at the point of greatest concen- 

 tration. A more serious drawback is the toxic action of some of the 

 drugs of the cinchona series. Moore and Chesny, 910 in an analysis 

 of the manifestations observed during optochin treatment of lobar 

 pneumonia in man, pointed out the well-known tendency of opto- 

 chin to damage eyesight. The authors stated that in the literature 

 on optochin treatment, among the patients developing serious oph- 

 thalmic disturbances with impairment of vision (4.5 per cent of 

 those reported) there were some whose iris failed to react to light 

 and others in whom the ophthalmoscope revealed a tortuosity of 

 the retinal vessels with a general constriction of the arteries. Acute 

 retinitis accompanied by temporary blindness has been observed, 

 but interference with vision is rarely permanent. Browning 159 has 

 stated that this complication has occurred mainly after adminis- 

 tration of the soluble hydrochloride and may be minimized by 

 avoiding excessive doses or by the use of relatively insoluble forms 

 of the drug. However, the comparative insolubility of the base 



