Inhibition of serotonin-induced ACTH release in man by clonidine.
1. Clonidine, an alpha 2-adrenergic agonist, is thought to inhibit noradrenergic neuronal activity (NNA) in the central nervous system (CNS) by a presynaptic alpha 2-receptor mechanism. Central NNA is thought to be the primary monoaminergic stimulus to pituitary ACTH release. Fenfluramine, a serotonin releasing agent and uptake inhibitor, causes ACTH release in normal man. 2. The present study investigated the effect of clonidine on fenfluramine-induced ACTH release in six normal volunteers. Four protocols were used: 1.5 mg/kg body weight oral fenfluramine; 4.3 micrograms/kg body weight oral clonidine; oral clonidine + oral fenfluramine 1 h later; placebo clonidine. Plasma ACTH and cortisol were measured at intervals for 5 h after clonidine and for 4 h after fenfluramine. 3. The mean plasma ACTH and cortisol levels and the mean maximal changes in these levels were significantly lower during the clonidine + fenfluramine test than during fenfluramine alone. Plasma ACTH and cortisol levels were not lowered significantly more by clonidine than by placebo. 4. In conclusion, clonidine blocked the ACTH-releasing activity of fenfluramine in normal humans. This inhibition of active ACTH release may result from clonidine blockade of fenfluramine-induced activation of central NNA. Clonidine alone was no more effective than placebo in lowering plasma ACTH and cortisol.
Jackson
R V
RV
Department of Medicine, Greenslopes Hospital, Brisbane, Queensland, Australia.
Grice
J E
JE
Jackson
A J
AJ
Vella
R D
RD
Armour
M B
MB
D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003000:Clonidine / Q000494:pharmacology*; D005260:Female; D005277:Fenfluramine / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D008875:Middle Aged; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists
D012702:Serotonin Antagonists; D005277:Fenfluramine; D012701:Serotonin; D000324:Adrenocorticotropic Hormone; D003000:Clonidine; D006854:Hydrocortisone