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-deoxycortiso…