Effects of loperamide on the human hypothalamo-pituitary-adrenal axis in vivo and in vitro

Loperamide, an opiate agonist of high specificity for p-receptors, recently reported to suppress ACTH and cortisol levels in normal , but not in patients with proven ACTH-dependent Cushing’s . However, there is little information on the site of action of in the hypothalamo-pituitary-adrenal axis of man. We the effect of loperamide on pituitary hormone secretion in and in vitro. In seven normal subjects, basal ACTH plasma levels significantly suppressed 3 h after loperamide administration (16 , orally) from 5 + 1 to 2 f 0 pmol/L (P < 0.0001). After the combined stimulation test (100 pg human CRH, 100 rg GnRH, 100 pg -releasing hormone, and 200 pg TRH), the ACTH peak (maximum at 30 min) was significantly blunted by loperamide from 9 + 1 to 4 of: 1 pmol/L (P < 0.001) and the area under the curve of ACTH O-120 min was reduced from 35 + 5 to 23 + 4 pmol/L.2 h (P < 0.05). In the insulin-hypoglycemia test (0.15 IU/kg BW), neither the peak nor the area under the curve of ACTH was affected by . In six patients with Cushing’s disease and one patient with adrenal insufficency due to hypothalamic failure, neither ACTH and cortisol levels nor CRH-stimulated levels were influenced loperamide. In four cultured human corticotropic adenomas, was not able to reduce basal and CRH-induced ACTH . In summary, loperamide is able to reduce basal and CRHinduced and cortisol levels in normal subjects, but not in with Cushing’s disease or secondary adrenal failure of hypothalamic . Loperamide has no significant effect on insulin-hypoglycemia- ACTH and cortisol levels and, therefore, no effect stress-induced elevation of cortisol levels. Loperamide might act at suprapituitary site in man in viuo, but, nevertheless, a pituitary site be excluded.