Naloxone-induced ACTH release in man is inhibited by clonidine

1. Adrenergic mechanisms play an important role in regulation of ACTH release. We used the alpha 2-adrenergic agonist, clonidine, as a central nervous system inhibitor of ACTH release to see if it would alter naloxone-induced ACTH secretion in normal human volunteers. 2. There was a significant blunting of the mean peak level of ACTH and the mean peak change of ACTH from basal as well as the area under the ACTH-time curve when clonidine was given prior to naloxone. 3. We conclude that clonidine, by blocking central noradrenergic pathways, which stimulate corticotropin-releasing hormone secretion, inhibits naloxone-induced ACTH secretion. This suggests that naloxone causes ACTH release through these same central noradrenergic pathways.