72 MEMBRANE PERMEABILITY AND DRUG ACTION 



glucoside would ensure ioo% survival with treatment 

 begun not less than 4 hours after contamination and 

 50% survival with treatment begun not less than 6^ 

 hours after contamination. Untreated animals die in 

 about 12 hours. 



In the first experiments with this compound, point 3 

 of the specification was assumed to be sufficiently met 

 by the diffusibility of the arsenic itself, which would 

 cause the arsenic to be trapped by the dithiol in the 

 blood stream. Later an attempt was made to increase the 

 diffusibility of the arsenic by administering small amounts 

 of B.A.L. This can penetrate readily into cells and there 

 combines with the arsenic which was hitherto combined 

 with intracellular proteins. It was thought that as a result 

 of this process arsenic would diffuse much more readily 

 into the blood stream and would there be trapped by 

 the large concentration of b.a.l. glucoside. It was in fact 

 found that amounts of b.a.l. which were too small to 

 affect the percentage of survival when given alone, and 

 which were too small to exercise a toxic effect, would 

 markedly increase the efficiency of the glucoside. 



It will be apparent from what has been said in this 

 chapter that, even with our present limited knowledge of 

 the permeability of mammalian tissues, it should often 

 be possible to reach valuable conclusions about the 

 action of a drug and the design of new drugs. In particu- 

 lar it is often possible to decide whether the permeability 

 factor is limiting the effectiveness of a drug, and to decide 



