Phenylthiazinothiamine, a New Thiamine Antagonist

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The anti-thiamine effect of phenylthiazinothiamine (PTT) was studied in the rat. The administration of PTT, a daily dose of 1.1mg per rat by oral or parenteral route, caused a loss in body weight and decrease in thiamine content in the brain of the animals reared on a thiamine deficient diet and supplemented with 5μg per day of thiamine. The anti-thiamine effect of PTT was more pronounced when it was given by oral route than by intraperitoneal route. Co-administration of PTT with thiamine (molar ratio, 200:1) by oral route evoked severe neuro-muscular symptoms of athiaminosis in all of the animals. These results suggest that PTT exerts its anti-thiamine effect not only by inhibiting the absorption of thiamine from the intestinal tract but also by antagonizing thiamine metabolism at the cellular level.A remarkable increase in thiamine content of the liver observed in the PTT treated rats was considered to be an artefact. It might be explained that a metabolite of PTT which specifically accumulated in the liver and has no thiamine activity in the organism was converted to thiamine or related compound during the determining procedure.
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