Stress-mediated effect of metoclopramide on cortisol secretion in man

Five healthy adult men were given metoclopramide (10 and 20 mg) iv, and in repeated tests almost always developed transient restlessness lasting from 10-30 min. The effects of L-dopa and dexamethasone on metoclopramide-induced increases in cortisol concentration were determined. These response values were compared with those of a control. After an injection of 10 mg metoclopramide, the cortisol level increased significantly only at 40 min; the ACTH level did not change. The cortisol rise was suppressed by dexamethasone pretreatment. Pretreatment with 0.5 g L-dopa resulted in a decrease in the PRL level from -20 min to 20 min, and the increase in cortisol seen at 40 min was cancelled. The ACTH level did not change. After injecting 20 mg metoclopramide, the ACTH level increased significantly from 20 min to 60 min and the cortisol level showed a significant increase from 20 min to 120 min. Pretreatment with dexamethasone resulted in a decrease in these hormones. The L-dopa pretreatment did not reduce even the rise in the PRL level which resulted from the administration of 20 mg metoclopramide. These findings suggest that the ACTH and cortisol response to metoclopramide is a stress-mediated effect. Plasma cortisol responses to 20 mg metoclopramide and insulin-induced hypoglycemia were studied and compared in seven volunteers and found to be similar.