Possible Role of Hydrazine Group in Hypoglycemia Associated with the Use of Certain Monoamine-oxidase Inhibitors (MAOI's)

It has been reported that some patients treated chronically with certain monoamine-oxidase inhibitors (MAOI's) exhibit as a complication hypoglycemia, or potentiation of insulin or sulfonylurea induced hypoglycemia. This effect has been attributed to interference by the MAOI with the hyperglycemic role of the sympathoadrenal system in glucose homeostasis, possibly through replacement of endogenous stored catecholamines by impotent “false transmitter.” These hypotheses lead to certain expectations, none of which were realized in the present experiments. Instead, evidence was obtained that it is the hydrazine group present in certain MAOI's, rather than their MAOI activity, to which hypoglycemic action should be attributed. Hydrazine and the hydrazine MAOI, phenelzine, induced similar decreases in plasma glucose and insulin levels of overnight fasted rats; phenelzine induced increases in plasma FFA levels. The nonhydrazine MAOI, pargyline, induced marked increases in plasma glucose levels.