Hypothalamic and medullary lesions caused by an aliphatic triamine unrelated to goldthioglucose

A single subcutaneous injection of 3.3'-methyliminobis-(N-methylpropylamine) caused edema and necrosis in the hypothalamus and medulla oblongata of rats, mice, and gerbils. Most other aliphatic triamines were ineffective. The lesions were very similar in character and distribution to those caused by goldthioglucose or bipiperidyl mustard. When compared to closely-related analogs, the biological activity of each of these three compounds is determined by a highly specific chemical structure, yet they have no structural similarities to each other. These data cast doubt on the theory that goldthioglucose causes lesions and, eventually, obesity by binding to a hypothalamic glucoreceptor. Alternatively, the localization of brain damage in hypothalamus and medulla has been attributed to proximity to median eminence and area postrema, and to the lack of a blood-brain barrier in the latter structures. This theory is supported by our finding that artificial disruption of blood-brain barrier in the cerebral cortex induced the localization of necrosis from the triamine in that area. Furthermore, these experiments provide evidence for the role of ischemia in the development of necrotic triamine-induced lesions.