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Changes in sleep electroencephalogram and nocturnal hormone secretion after administration of the antidyskinetic agent sarizotan in healthy young male volunteers

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Abstract

Rationale

Sarizotan is a 5-HT1A agonist with high affinity to D3 and D4 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-HT1A 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.

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Acknowledgements

We like to thank Merck KGaA, Darmstadt, Germany, for their support of the study and Mrs. Jutta Drancoli-Quante, our technician, for her help in organising the study.

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Authors and Affiliations

  1. Department of Psychiatry, Max Planck Institute of Psychiatry, Kraepelinstrasse 2-10, 80804, Munich, Germany

    Heike E. Kuenzel, Axel Steiger, Katja Held, Irina A. Antonijevic, Ralf-Michael Frieboes & Harald Murck

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  1. Heike E. Kuenzel
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  2. Axel Steiger
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  3. Katja Held
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  4. Irina A. Antonijevic
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  5. Ralf-Michael Frieboes
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  6. Harald Murck
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Correspondence to Axel Steiger.

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Kuenzel, H.E., Steiger, A., Held, K. et al. Changes in sleep electroencephalogram and nocturnal hormone secretion after administration of the antidyskinetic agent sarizotan in healthy young male volunteers. Psychopharmacology 180, 327–332 (2005). https://doi.org/10.1007/s00213-005-2160-3

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  • DOI: https://doi.org/10.1007/s00213-005-2160-3

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