S-Alkoxycarbonylthiamineのラットにおける致死機構の解析

抄録

As the so-called "mass therapy" by new thiamine derivatives are frequently carried out with some clinical improvements, it is very important to clarify the mode of acute toxicity of these thiamine derivatives. By continuous intravenous infusion of thiamine derivatives in rats under artificial respiration, it was proved that the activity in respiratory arrest decreased in the following order : O-ethoxycarbonylthiamine (OCET)>thiamine(B₁-HCI)>thiamine tetrahydrofurfuryldisulfide (TTFD)>O, S-bisethoxycarbonylthiamine (DCET)>S-butoxycarbonylthiamine (CBT)>S-ethoxycarbonylthiamine (CET)>thiamine disulfide. Even under artificial respiration, cardiac arrest was observed by the intravenous infusion of CBT and DCET in 100 mM saline solution. No cardiac arrest, however, was seen by the intravenous infusion of B₁-HCl and OCET saline solution under artificial respiration. It was proved that cardiac arrest following DCET administration was most intimately related to the DCET concentration in blood plasma, because the equimolar administration of B₁-HCl, OCET, or CET caused no cardiac arrest in rats. Twitch potentiation caused by S-alkoxycarbonylthiamine (S-CAT) in the striated muscle was considered as being one of the possible causes for weak toxicity because, marked respiratory excitement was observed by S-CAT administration. Comparing the effects of various thiamine derivatives-thiazole, thiole, and disulfide type thiamine-, it was confirmed that the twitch potentiation in the curarized rat isolated diaphragm was mainly observed when S-CAT was administered.