Changes in sleep electroencephalogram and nocturnal hormone secretion after administration of the antidyskinetic agent sarizotan in healthy young male volunteers.
BACKGROUND
Sarizotan is a 5-HT(1A) agonist with high affinity to D(3) and D(4) receptors. In animal experiments, the drug shows a strong anti-cataleptic effect and suppresses effectively dyskinesias in animal models of L: -dopa-induced dyskinesia and of tardive dyskinesia. Data from an open pilot study in patients with Parkinson's disease show clear indication of a treatment effect against L: -dopa-induced dyskinesia.


OBJECTIVE
CNS-active drugs are known to modulate sleep electroencephalogram (EEG) and sleep-related hormone secretion. 5-HT(1A) agonists suppress rapid-eye movement (REM) sleep and enhance the secretion of ACTH, cortisol, prolactin and growth hormone (GH) at daytime. We hypothesised that sarizotan shares these effects. Furthermore, we were interested in the influence of sarizotan on leptin, which participates in the regulation of the energy balance and is enhanced after various psychoactive drugs.


METHODS
Ten healthy male subjects were investigated twice in a double-blind, placebo-controlled crossover design. Sleep EEG and nocturnal hormone secretion of ACTH, cortisol, prolactin, GH and leptin were examined after oral administration of either placebo or 20 mg of sarizotan at night.


RESULTS
After administration of sarizotan, a significant reduction of REM sleep and total sleep time in conventional sleep EEG and a significant reduction of sigma- and theta-power in spectral analysis were observed. The main effect on nocturnal hormone secretion was a significant elevation of prolactin and of ACTH in the first half of the night.


CONCLUSIONS
While REM sleep was suppressed, the endocrine effects of 20 mg sarizotan at night were weak. Its sleep-endocrine profile is comparable to the effects provoked by selective 5-HT reuptake inhibitors.
Kuenzel
Heike E
HE
Department of Psychiatry, Max Planck Institute of Psychiatry, Kraepelinstrasse 2-10, 80804, Munich, Germany.
Steiger
Axel
A
Held
Katja
K
Antonijevic
Irina A
IA
Frieboes
Ralf-Michael
RM
Murck
Harald
H
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D004311:Double-Blind Method; D004569:Electroencephalography / Q000187:drug effects*; D006728:Hormones / Q000097:blood*; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D020738:Leptin / Q000097:blood; D008297:Male; D009930:Organic Chemicals / Q000494:pharmacology; D011388:Prolactin / Q000097:blood; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D012890:Sleep / Q000502:physiology*
D006728:Hormones; D020738:Leptin; D009930:Organic Chemicals; D017366:Serotonin Receptor Agonists; D019382:Human Growth Hormone; C443959:sarizotan; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D006854:Hydrocortisone
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