Effect of serotonin uptake inhibition by zimelidine on hypothalamic-pituitary-adrenal activity.
Plasma ACTH levels after oral ingestion of 2 g metyrapone at 24.00 hours in six healthy subjects were higher after pretreatment with zimelidine (300 mg) in comparison to placebo. Since zimelidine is a relatively selective serotonin reuptake inhibitor its action on hypothalamic-pituitary-adrenal (HPA) activity suggests that serotonin is a potent stimulator of ACTH release. The ratio of cortisol to 11-deoxycortisol was taken as a measure of 11-hydroxylase activity, which indicates biological activity of secreted ACTH. These cortisol/11-deoxycortisol ratios were significantly increased after zimelidine treatment, when compared to placebo. Both the ACTH response and the cortisol/11-deoxycortisol ratios substantiate evidence derived from animal experiments, indicating a stimulatory influence of serotonin on HPA activity. No firm conclusion, however, may be drawn on by which mechanism zimelidine exerts its action on the HPA-axis. Moreover these findings provide no information on whether serotonin has a stimulatory role on ACTH production under physiological condition.
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D001692:Biological Transport / Q000187:drug effects; D001977:Brompheniramine / Q000031:analogs & derivatives; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology*; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000502:physiology*; D010919:Placebos; D011725:Pyridines; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists; D015031:Zimeldine
D010919:Placebos; D011725:Pyridines; D012702:Serotonin Antagonists; D012701:Serotonin; D015031:Zimeldine; D000324:Adrenocorticotropic Hormone; D001977:Brompheniramine