PERMEABILITY FACTOR IN DRUG ACTION 69 



to show that the following relationship should hold: 



'' — = constant approximately. 



B 



Table xvi shows a small selection of the experimental 

 data, including the most toxic, the least toxic and several 

 intermediate compounds of the arsenoxide type.Whereas 

 the value of the lethal dilution varies by a factor of 5,000 

 fold, the value of (L.D)M^^^IB variesby only twelve fold, 

 i.e. of the variation in the L.D., practically the whole 

 is accounted for by the variation in permeability. Thus the 

 organic chemists, in synthesising a wide range of arsen- 

 oxides, were unwittingly studying the permeability of 

 trypanosomes and little else. 



The Chemotherapy of Lezoisite Poisoning. In a series of 

 biochemical studies Peters, Stocken and Thompson 

 found evidence that lewisite exercises its toxicity by 

 combining with the SH groups of enzymes. By studying 

 the ease with which lewisite may be detached from the 

 compound it forms with kerateine, they concluded that 

 lewisite must often combine not merely with one, but 

 with two thiol groups of the protein molecule. Conse- 

 quently they argued that to obtain a substance which 

 would compete efficiently with tissue enzymes for lewi- 

 site, and thus constitute an efficient therapeutic reagent , 

 it would be necessary to have a dithiol grouping. Voegtlin 

 and QuASTEL had both shown earlier that monothiols can 

 prevent or reverse some of the toxic action of arsenoxides. 



