Bretazenil modulates sleep EEG and nocturnal hormone secretion in normal men

Güldner, J.; Trachsel, L.; Kratschmayr, C.; Rothe, B.; Holsboer, Florian; Steiger, Axel

doi:10.1007/bf02246085

Cited by 12 publications

(6 citation statements)

References 37 publications

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“…Diazepam 0.5 mg / kg decreased ACTH plasma levels after a single dose and decreased ACTH and corticosterone after repeated administration in the rat (Bruni et al 1980). During sleep, orally administered bretazenil (1 mg) in men decreased cortisol secretion (Guldner et al 1995). Our Þnding of a blunting of ACTH is compatible with an NMDA-antagonistic and a GABA A -agonistic e¤ect of Mg 2+ .…”

Section: Discussionmentioning

confidence: 58%

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Mg 2+ reduces ACTH secretion and enhances spindle power without changing delta power during sleep in men - possible therapeutic implications

Murck¹,

Steiger²

1998

Psychopharmacology

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Disturbances of Mg2+ metabolism have been reported in association with affective disorders, seizures in eclampsia, and alcohol withdrawal. Mg2+ has been reported to have N-methyl-D-aspartate (NMDA)-antagonistic and gamma-aminobutyric acid (GABA)-agonistic properties and modulation of GABA(A)- and NMDA-dependent systems is involved in pharmacological treatment of affective disorders and seizures. We studied the effect of Mg2+ on sleep electroencephalogram (EEG) and nocturnal hormonal secretion in men. Ten normal controls were given MgSO4 (3 g MgSO4 between 2030 hours and 2100 hours, followed by 0.5 g MgSO4 per hour until 0700 hours) or placebo i.v. according to a randomized schedule. The sleep EEG was recorded from 2300 hours to 0700 hours. Blood samples were taken from 2000 hours to 0700 hours for analysis of plasma corticotropin (ACTH), cortisol, growth hormone, prolactin and melatonin. The sleep-EEG power within the spindle frequency range (11.0-12.9 Hz) showed a significant increase in the third sleep cycle, but delta power was unchanged throughout the night. ACTH concentration was suppressed between 2200 hours and 0700 hours. No changes in cortisol, growth hormone prolactin or melatonin release were found. The findings are consistent with the assumption that Mg2+ has GABA(A)-agonistic or NMDA-antagonistic effects on sleep and nocturnal hormonal secretion and hence may be useful in controlling depressive symptoms and seizures.

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Section: Discussionmentioning

confidence: 58%

“…A detailed description of the conventional sleep analysis and the methodology of the spectral analysis is described elsewhere (Guldner et al 1995).…”

Section: Sleep-eeg Analysismentioning

confidence: 99%

Mg 2+ reduces ACTH secretion and enhances spindle power without changing delta power during sleep in men - possible therapeutic implications

Murck¹,

Steiger²

1998

Psychopharmacology

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“…The development of some compounds, such as the benzodiazepine receptor partial agonist bretazenil (a benzodiazepine derivative) 45,46 and the GABA A receptor α2 and α3 subunit agonist SL651498 (REF. 47), was discontinued owing to unexpected sedative and/or amnestic effects.…”

Section: Gaba–benzodiazepine Systemmentioning

confidence: 99%

50 years of hurdles and hope in anxiolytic drug discovery

Griebel

Holmes

2013

Nat Rev Drug Discov

383

346

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Anxiety disorders are the most prevalent group of psychiatric diseases, and have high personal and societal costs. The search for novel pharmacological treatments for these conditions is driven by the growing medical need to improve on the effectiveness and the side effect profile of existing drugs. A huge volume of data has been generated by anxiolytic drug discovery studies, which has led to the progression of numerous new molecules into clinical trials. However, the clinical outcome of these efforts has been disappointing, as promising results with novel agents in rodent studies have very rarely translated into effectiveness in humans. Here, we analyse the major trends from preclinical studies over the past 50 years conducted in the search for new drugs beyond those that target the prototypical anxiety-associated GABA (γ-aminobutyric acid)–benzodiazepine system, which have focused most intensively on the serotonin, neuropeptide, glutamate and endocannabinoid systems. We highlight various key issues that may have hampered progress in the field, and offer recommendations for how anxiolytic drug discovery can be more effective in the future.

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“…Although the data are inconsistent, benzodiazepine hypnotics seem to affect hormonal secretions. Various studies have found a suppression of cortisol or, less desirable, of GH and a stimulation of prolactin (4,12,27).…”

mentioning

confidence: 99%

Effect of the GABA_A agonist gaboxadol on nocturnal sleep and hormone secretion in healthy elderly subjects

Lancel

Wetter

Steiger

et al. 2001

American Journal of Physiology-Endocrinology and Metabolism

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Aging is associated with a dramatic decrease in sleep intensity and continuity. The selective GABA(A) receptor agonist gaboxadol has been shown to increase non-REM sleep and the duration of the non-REM episodes in rats and sleep efficiency in young subjects and to enhance low-frequency activity in the electroencephalogram (EEG) within non-REM sleep in both rats and humans. In this double-blind, placebo-controlled study, we investigated the influence of an oral dose of 15 mg of gaboxadol on nocturnal sleep and hormone secretion (ACTH, cortisol, prolactin, growth hormone) in 10 healthy elderly subjects (6 women). Compared with placebo, gaboxadol did not affect endocrine activity but significantly reduced perceived sleep latency, elevated self-estimated total sleep time, and increased sleep efficiency by decreasing intermittent wakefulness and powerfully augmented low-frequency activity in the EEG within non-REM sleep. These findings indicate that gaboxadol is able to increase sleep consolidation and non-REM sleep intensity, without disrupting REM sleep, in elderly individuals and that these effects are not mediated by a modulation of hormone secretion.

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Bretazenil modulates sleep EEG and nocturnal hormone secretion in normal men

Cited by 12 publications

References 37 publications

Mg 2+ reduces ACTH secretion and enhances spindle power without changing delta power during sleep in men - possible therapeutic implications

Mg 2+ reduces ACTH secretion and enhances spindle power without changing delta power during sleep in men - possible therapeutic implications

50 years of hurdles and hope in anxiolytic drug discovery

Effect of the GABA_A agonist gaboxadol on nocturnal sleep and hormone secretion in healthy elderly subjects

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Bretazenil modulates sleep EEG and nocturnal hormone secretion in normal men

Cited by 12 publications

References 37 publications

Mg 2+ reduces ACTH secretion and enhances spindle power without changing delta power during sleep in men - possible therapeutic implications

Mg 2+ reduces ACTH secretion and enhances spindle power without changing delta power during sleep in men - possible therapeutic implications

50 years of hurdles and hope in anxiolytic drug discovery

Effect of the GABAA agonist gaboxadol on nocturnal sleep and hormone secretion in healthy elderly subjects

Contact Info

Product

Resources

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Effect of the GABA_A agonist gaboxadol on nocturnal sleep and hormone secretion in healthy elderly subjects