Abstract
Intraperitoneal administration of benzenesulfonylthiamine disulfide (I) (5mg equivalent to thiamine-HCI) to rats resulted in such a low urinary thiamine excretion in 24 hours as 3% of the dosage, suggesting destruction of I in animals instead of the reduction to benzenesulfonylthiamine (II). On incubation of I with the homogenate of rat liver at pH 6.0 for 3 hours, the majority of I was decomposed, showing less than 10% the recovery of I, while on the incubation at pH 4.5,I was more stable and more than 75% of I were recovered as II. The reaction was shown to be non-enzymatic, because the boiled homogenate was also capable of decomposition and reduction. The reduction of I to II by cysteine or thioglycolic acid was checked at the ranges of pH between 3 and 8 : A quantitative recovery to II was observed only at pH 3-4 and such a poor recovery less than 10% at the higher pH than 6 was shown with the simultaneous formation of thiamine-anhydride which was isolated as crystals of mp. 110℃. When I was given intraperitoneally to rats, I was probably decomposed to thiamine-anhydride and its further metabolites, and only a metabolite similar but not identical to thiamine-anhydride sulfoxide was detected on its paper chromatogram. Biological activity of I to thiamine-deficient rats, was proved to be non-effective for growth-stimulation at the dosage of 20μg equivalent to thiamine-HCl on every other day, but at the 200μg level, I was shown to be effective by both oral and intraperitoneal administration.
