Rutman R J, Lewis F S, Bloomer W D
Science. 1966 Aug 26;153(3739):1000-2. doi: 10.1126/science.153.3739.1000.
Bipiperidyl mustard, after conversion to its bis-cyclic immonium ion forme, has been found to cause rapid and extensive lipid deposition in mice given single doses of the drug. The obe sity appears to result from an alkylation reaction; the responses of the treated ani mals to food restriction and realimenta tion resemble those observed in gold thioglucose-treated mice; also in anal ogy to gold thioglucose, the bipiperidyl mustard effects can be counteracted by sulfhydryl compounds. These observa tions are suggestive of a similarity of mode of action between the alkylating agent and gold thioglucose, a conclusion which is supported by preliminary find ings of ventromedial lesions in the hypo thalamus of the bipiperidyl mustard treated mice.
双哌啶基芥子气转化为其双环亚胺离子形式后,已发现单剂量给药的小鼠体内会迅速且广泛地出现脂质沉积。肥胖似乎是由烷基化反应导致的;经处理的动物对食物限制和再喂养的反应类似于硫代葡萄糖金处理的小鼠;同样与硫代葡萄糖金类似,双哌啶基芥子气的作用可被巯基化合物抵消。这些观察结果表明烷基化剂与硫代葡萄糖金的作用方式相似,这一结论得到了双哌啶基芥子气处理小鼠下丘脑腹内侧病变的初步发现的支持。