6533b820fe1ef96bd1279a51
RESEARCH PRODUCT
Effect of serotonin uptake inhibition by zimelidine on hypothalamic-pituitary-adrenal activity
Helmuth G. DoerrO.a. MüllerFlorian HolsboerK. WinterWolfgang G. Sippellsubject
AdultMaleHypothalamo-Hypophyseal SystemSerotoninendocrine systemmedicine.medical_specialtySerotonin uptakePyridinesSerotonin reuptake inhibitorPituitary-Adrenal SystemPharmacologyPlaceboPlacebosAdrenocorticotropic HormoneInternal medicinemedicineHumansZimelidinePharmacologyMetyraponeChemistryPhysiological conditionZimeldineBiological TransportBiological activityBrompheniramineEndocrinologySerotonin AntagonistsSerotoninhormones hormone substitutes and hormone antagonistsmedicine.drugdescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 1983-04-01 | Psychopharmacology |