Abstract
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-pituitaryadrenal (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.
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References
Benkert O, Laakmann G, Ott L, Strauss A, Zimmer R (1977) Effect of zimelidine (H102/09) in depressive patients. Arzneim Forsch 27 (II):2421–2423
Bradley JV (1968) Distribution-free statistical tests. Prentice Hall, Englewood Cliffs, pp 315–317
Carroll BJ (1982) The dexamethasone suppression test for melancholia. Br J Psychiatry 140:292–304
Coppen A, Rama Rao VA, Swade C, Wood K (1979) Zimelidine: A therapeutic and pharmacokinetic study in depression. Psychopharmacology 63:199–202
Fuller RW (1981) Serotonergic stimulation of pituitary-adrenocortical function in rats. Neuroendocrinology 32:118–127
Ganguly A, Meikle AW, Tyler FH, West CD (1977) Assessment of 11β-hydroxylase activity with plasma corticosterone, deoxycorticosterone, cortisol and deoxycortisol: Role of ACTH and angiotensin. J Clin Endocrinol Metab 44:560
Holsboer F, Liebl R, Hofschuster E (1982) Repeated dexamethasone suppression test during depressive illness: normalisation of test result compared with clinical improvement. J Affect Dis 4:93–101
Jones MT, Hillhouse EW, Barden J (1976) Effect of various putative neurotransmitters on the secretion of corticotropin-releasing hormone from the rat hypothalamus in vitro — a model of the neurotransmitters involved. J Endocrinol 69:1–10
Liddle GW, Island D, Lance EM, Harris AP (1958) Alterations of adrenal steroid patterns in man resulting from treatment with a chemical inhibitor of 11β-hydroxylation. J Clin Endocrinol Metab 18:906–912
Müller OA, Fink R, Baur X, Ehbauer M, Madler M, Scriba PC (1978) ACTH im Plasma: Extraktion und Bestimmung. GIT-Labormed 2:117–124
Ross SB, Hall H, Renyi AL, Westerlund D (1981) Effects of zimelidine on serotonergic and noradrenergic neurons after repeated administration in the rat. Psychopharmacology 72:219–225
Sippell WG, Bidlingmaier F, Becker H, Brünig T, Doerr H, Hahn H, Golder W, Hollmann G, Knorr D (1978) Sindultaneous radio-immunoassay of plasma aldosterone, corticosterone, 11-deoxycorticosterone, progesterone, 17-hydroxyprogesterone, 11-deoxycortisol, cortisol and cortisone. J Steroid Biochem 9:63–73
Strott CA, West CD, Nakasawa K, Kondo T, Tyler FH (1969) Plasma 11-deoxycorticosteroid and ACTH response to metyrapone (plasma metyrapone test). J Clin Endocrinol Metab 29:6–11
Syvälahti E, Eneroth P, Ross SB (1979) Acute effects of zimelidine and alaproclate, two inhibitors of serotonin uptake, on neuroendocrine function. Psychiatr Res 1:111–120
Weiner RI, Ganong WF (1978) Role of brain monoamines and histamine in regulation of anterior pituitary secretion. Physiol Rev 58:9905–976
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This study was conducted at the Department of Psychiatry, University of Munich, Germany
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Holsboer, F., Müller, O.A., Winter, K. et al. Effect of serotonin uptake inhibition by zimelidine on hypothalamic-pituitary-adrenal activity. Psychopharmacology 80, 85–87 (1983). https://doi.org/10.1007/BF00427502
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DOI: https://doi.org/10.1007/BF00427502