70 MEMBRANE PERMEABILITY AND DRUG ACTION 



The danger from lewisite usually arises from skin con- 

 tamination. Consequently to prevent vesication by lewi- 

 site, it is necessary to have a dithiol which will readily 

 penetrate the skin. To attain reasonably fast permeation 

 of skin, it is necessary to have a small molecule, having 

 a moderate oil-water partition coefficient. Glycerol a, /5- 

 dithiol, later known as b.a.l.^ conforms to this specifica- 

 tion and was found to be very effective as an antidote to 

 the vesicant action of lewisite. 



B.A.L. also has value as an agent for systemic arsenical 

 poisoning. But this is limited by the toxicity of b.a.l. 

 itself. The maximum dose of b.a.l. which may be ad- 

 ministered to man is 4 mg/kg/4 hrs. This is consider- 

 ably below the amount of dithiol which would be needed 

 to secure efficient therapeutic action in a serious case 

 of systemic lewisite poisoning. Consequently an attempt 

 was made to obtain a substance which would be an effi- 

 cient antidote for systemic poisoning. The points in the 

 molecular specification for such a substance were: 



1 . It should inactivate arsenic. 



2. It should have a low toxicity. 



3. It should remove arsenic from cells into which arsenic 

 has penetrated. 



4. It should penetrate the whole of the lymph and 

 vascular spaces. 



5. The complex formed with arsenic should be readily 

 excreted. 



^ B.A.L. for British Anti-Lewisite. 



