Antithiamine Activity of Dimethialium and Its Mode of Action

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Abstract
The antithiamine activity of dimethialium, a thiamine analogue having a methyl group in place of the hydroxyethyl group in the thiazole moiety, has been demonstrated in nutritional assays using rats or chicks. The antagonism was evident only when thiamine was administered orally. The inhibition was competitive with thiamine or thiamine propyl disulfide. The latter counteracted the antithiamine activity of dimethialium two to four times more effectively than did thiamine. Thiamine uptake in vitro by Ehrlich ascites carcinoma cells was inhibited competitively by dimethialium, whereas the uptake of thiamine tetrahydrofurfuryl disulfide was not affected. Dimethialium inhibited thiaminokinase competitively with thiamine but showed little or no effect upon pyruvate decarboxylation by carboxylase or pyruvate oxidase complexes. All these results demonstrate that dimethialium is a typical but relatively weak antithiamine whose antagonistic activity is far less than that of pyrithiamine and comparable to that of amprolium. The present data also support the view that the primary cause of the antithiamine action is its interference with intestinal absorption or cellular uptake of thiamine.