Antiglucocorticoid treatment disrupts endocrine cycle and nocturnal sleep pattern.
Mifepriston (RU 486) is a steroid antagonist which binds with high affinity to glucocorticoid receptors (GR), and also to progesterone receptors. The antiglucocorticoid action of Mifepriston in man has been demonstrated by blockade of the negative feedback action of endogenous cortisol and by antagonism of the effects of exogenously administered dexamethasone. In the present study Mifepriston was administered to a normal male volunteer at 14.00 h and its effects on pituitary-adrenal activity and nocturnal sleep pattern were recorded. Mifepriston caused a large rise in plasma ACTH levels during the morning hours in comparison to untreated male control subjects. Plasma ACTH levels in the Mifepriston treated subject at 7.00 h were threefold greater than in the control subjects (104.4 pg/ml vs. 37.6 +/- 13.9 pg/ml; mean +/- SD). Subsequently the cortisol secretion was enhanced and the rise was advanced by about 60 minutes compared to controls. The main effects of Mifepriston on EEG sleep pattern were a dramatic disruption of sleep quality with a prolonged sleep onset latency, increased nocturnal awakenings and a considerable reduction of both slow wave sleep (SWS) and REM sleep. After Mifepriston, SWS was reduced by about 80% in comparison to placebo, and REM sleep was reduced by more than 50%. While the present data were collected from only a single subject the effects observed were so pronounced that tentative conclusions seem to be justified: The well-established pharmacological properties of Mifepriston as a glucocorticoid antagonist are reflected by its action on sleep physiology since it influences sleep in a direction opposite to that produced by cortisol.(ABSTRACT TRUNCATED AT 250 WORDS)
Wiedemann
K
K
Max Planck Institute of Psychiatry, Department of Psychiatry, Munchen, Federal Republic of Germany.
Lauer
C
C
Loycke
A
A
Pollmächer
T
T
Durst
P
P
Machér
J P
JP
Holsboer
F
F
D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000328:Adult; D001143:Arousal / Q000187:drug effects; D002940:Circadian Rhythm / Q000187:drug effects*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D008297:Male; D015735:Mifepristone / Q000494:pharmacology*; D011965:Receptors, Glucocorticoid / Q000187:drug effects*; D012894:Sleep Stages / Q000187:drug effects*; D012895:Sleep, REM / Q000187:drug effects
D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone