Modulation of glucose homeostasis by doxepin.

Blood glucose level (BGL) was estimated up to 4 h (3 h in case of GTT) in 18-h fasted albino rabbits following acute and chronic (one month) feeding of doxepin and thereafter for another 8 days together with either insulin or glibenclamide or adrenaline. A single dose of doxepin produced significant hypoglycemia which peaked at 4 h and lasted up to 10 h. On chronic doxepin feeding there was complete attenuation of initial hypoglycemia on the 7th and 14th days, culminating into frank hyperglycemia on the 21st day. However, there was complete recovery on the 29th day exhibiting tolerance to initial hypo-as well as delayed hyperglycemia. Similarly, glucose intolerance was accentuated on the 8th day followed by a gradual recovery on the 15th and 22nd days, culminating in disappearance of glucose intolerance on the 30th day. The hypoglycemic effect of insulin was markedly potentiated in chronically doxepin fed animals which was further enhanced on continuing administration of both agents. Profound hypoglycemia was observed during GTT in such animals. The hyperglycemic effect of adrenaline was enhanced in chronically doxepin fed animals, which may be due to TCA induced enhancement of the response of exogenous adrenaline. Suppression of this hyperglycemia with continued administration of both drugs seems to be due to subsensitivity of alpha 2-adrenoceptors. Additive hyperglycemia was observed during GTT in such animals.