STUDIES ON MECHANISMS OF ACTION OF CERTAIN ANTIDOTES AGAINST TRIVALENT ORGANIC ANTIMONIALS AND ON THE FATE OF ANTIMONY IN THE BLOOD

It has been shown that when tartar emetic (TE) is mixed with one of the 2 well- known antidotes, sodium 1,2-dihydroxy benzene 3,5-disulphonate (SDD) or sodium di- mercaptosuccinate (SMS), fouadin and sodium antimonyl dimercaptosuccinate will be formed, and that, when TE is mixed with sodium gluconate, cysteine or EDTA, the cor- responding antimonials will be formed. On the other hand, if fouadin, sodium anti- monyl dimercaptosuccinate, sodium Sb^III-gluconate, Sb^III-cysteine, or Sb^III-EDTA is se- parately added to a solution of tartrate, TE will also be formed in various amount. The in vitro effects of TE and fouadin on survival of schistosomes in Tyrode's solu- tion were studied. The antischistosomal activity of the antimonials were reduced by adding SDD, cysteine, sodium gluconate, sodium citrate or sodium tartrate. On the other hand, these drugs were shown to prevent the Sb of TE from combining with the blood cells. SMS or SDD was shown to be able to "rob" the Sb which already com- bined with the blood cells or schistosomes. When SDD and TE (molecular ratio, 2:1) were injected to the same mouse intra- peritoneally, the acute LD₅₀ was 32.1 mg/kg. When fouadin was administered alone, its acute LD₅₀ was 32.2 mg/kg. These results revealed that the mechanisms of antidotes against antimonials were to become the corresponding antimonials and to "rob" the Sb in TE or in tissues. On account of the fact that cysteine, glutathione, proteins or enzymes containing sulfphydryl groups and certain hydroxylic acids, such as lactate and citrate, etc., were found to exist in blood or tissues, these compounds may chelate with the Sb in antimonials. Therefore, the forms of Sb in the blood are to be decided by various relative materials and condi- tions.