Flumazenil exerts intrinsic activity on sleep EEG and nocturnal hormone secretion in normal controls |
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Authors: | A. Steiger J. Guldner C. J. Lauer C. Meschenmoser T. Pollmächer F. Holsboer |
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Affiliation: | (1) Department of Psychiatry, Max Planck Institute of Psychiatry, Clinical Institute, D-80804 München, Germany |
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Abstract: | The physiological function of benzodiazepine (BDZ) receptors includes regulation of sleep and neuroendocrine activity. Most of the pharmacological effects of BDZ are blocked by flumazenil. However, recent neurological and behavioral studies suggest that flumazenil has its own central intrinsic activity. This issue was addressed in a study of the sleep EEG and the nocturnal secretion of growth hormone and cortisol in ten normal male controls, who were given flumazenil either alone or in combination with the BDZ agonist midazolam, placebo and midazolam alone. Flumazenil prompted an increase in sleep onset latency, a decrease in slow wave sleep and an increase in wakefulness. Plasma cortisol concentrations after flumazenil administration were lower than after midazolam. Both flumazenil and midazolam decreased nocturnal growth hormone secretion. After simultaneous application of both BDZ receptor ligands the growth hormone blunting was amplified. Our study demonstrates that at the level of the sleep EEG and neuroendocrine activity flumazenil is capable of exerting both agonistic and inverse agonistic or antagonistic effects.Parts of this study were presented at the 69th Meeting of the Deutsche Physiologische Gesellschaft, Freiburg, 6–8 March, 1991 |
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Keywords: | Sleep EEG Cortisol Growth hormone Flumazenil Midazolam |
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