التفاصيل البيبلوغرافية
| العنوان: |
Differential sleep-promoting effects of dual orexin receptor antagonists and GABAA receptor modulators |
| المؤلفون: |
Gotter, Anthony L, Garson, Susan L, Stevens, Joanne, Munden, Regina L, Fox, Steven V, Tannenbaum, Pamela L, Yao, Lihang, Kuduk, Scott D, McDonald, Terrence, Uslaner, Jason M, Tye, Spencer J, Coleman, Paul J, Winrow, Christopher J, Renger, John J |
| بيانات النشر: |
BioMed Central Ltd. |
| سنة النشر: |
2014 |
| المجموعة: |
BioMed Central |
| مصطلحات موضوعية: |
Orexin, Hypocretin, Benzodiazepine, Insomnia, Sleep, Electroencephalography, Sleep deprivation, REM sleep, NREM sleep, Suvorexant, Belsomra |
| الوصف: |
Background The current standard of care for insomnia includes gamma-aminobutyric acid receptor A (GABA A ) activators, which promote sleep as well as general central nervous system depression. Dual orexin receptor antagonists (DORAs) represent an alternative mechanism for insomnia treatment that induces somnolence by blocking the wake-promoting effects of orexin neuropeptides. The current study compares the role and interdependence of these two mechanisms on their ability to influence sleep architecture and quantitative electroencephalography (qEEG) spectral profiles across preclinical species. Results Active-phase dosing of DORA-22 induced consistent effects on sleep architecture in mice, rats, dogs, and rhesus monkeys; attenuation of active wake was accompanied by increases in both non─rapid eye movement (NREM) and rapid eye movement (REM) sleep. Eszopiclone, a representative GABA A receptor modulator, promoted sleep in rats and rhesus monkeys that was marked by REM sleep suppression, but had inconsistent effects in mice and paradoxically promoted wakefulness in dogs. Active-phase treatment of rats with DORA-12 similarly promoted NREM and REM sleep to magnitudes nearly identical to those seen during normal resting-phase sleep following vehicle treatment, whereas eszopiclone suppressed REM even to levels below those seen during the active phase. The qEEG changes induced by DORA-12 in rats also resembled normal resting-phase patterns, whereas eszopiclone induced changes distinct from normal active- or inactive-phase spectra. Co-dosing experiments, as well as studies in transgenic rats lacking orexin neurons, indicated partial overlap in the mechanism of sleep promotion by orexin and GABA modulation with the exception of the REM suppression exclusive to GABA A receptor modulation. Following REM deprivation in mice, eszopiclone further suppressed REM sleep while DORA-22 facilitated recovery including increased REM sleep. Conclusion DORAs promote NREM and importantly REM sleep that is similar in proportion ... |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| Relation: |
http://www.biomedcentral.com/1471-2202/15/109 |
| الاتاحة: |
http://www.biomedcentral.com/1471-2202/15/109 |
| Rights: |
Copyright 2014 Gotter et al.; licensee BioMed Central Ltd. |
| رقم الانضمام: |
edsbas.2A8B174A |
| قاعدة البيانات: |
BASE |