Promotion of sleep by targeting the orexin system in rats, dogs and humans

doi:10.1038/nm1544

	Promotion of sleep by targeting the orexin system in rats, dogs and humans
	Brisbare-Roch, Catherine ; Dingemanse, Jasper ; Koberstein, Ralf ; Hoever, Petra ; Aissaoui, Hamed ; Flores, Susan ; Mueller, Celia ; Nayler, Oliver ; van Gerven, Joop ; de Haas, Sanne L.
刊名	NATURE MEDICINE
	2007-02
卷号	13 期号:2 页码:150-155
ISSN号	1078-8956
DOI	10.1038/nm1544
文献子类	Article
英文摘要	Orexins are hypothalamic peptides that play an important role in maintaining wakefulness in mammals. Permanent deficit in orexinergic function is a pathophysiological hallmark of rodent, canine and human narcolepsy. Here we report that in rats, dogs and humans, somnolence is induced by pharmacological blockade of both orexin OX1 and OX2 receptors. When administered orally during the active period of the circadian cycle, a dual antagonist increased, in rats, electrophysiological indices of both non-REM and, particularly, REM sleep, in contrast to GABA(A) receptor modulators; in dogs, it caused somnolence and increased surrogate markers of REM sleep; and in humans, it caused subjective and objective electrophysiological signs of sleep. No signs of cataplexy were observed, in contrast to the rodent, dog or human narcolepsy syndromes. These results open new perspectives for investigating the role of endogenous orexins in sleep-wake regulation.
WOS关键词	HYPOCRETIN OREXIN ; LOCUS-COERULEUS ; DIURNAL-VARIATION ; LATENCY TEST ; A LEVELS ; NARCOLEPSY ; NEURONS ; WAKEFULNESS ; MICE ; PEPTIDES
WOS研究方向	Biochemistry & Molecular Biology ; Cell Biology ; Research & Experimental Medicine
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000244031700023
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/273344]
专题	中国科学院上海药物研究所
通讯作者	Jenck, Francois
作者单位	1.Chinese Acad Sci, Inst Biol Sci, Actel Joint Labs, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 2.Actel Pharmaceut Ltd, Res & Dev, CH-4123 Allschwil, Switzerland 3.Ctr Human Drug Res, NL-2333 CL Leiden, Netherlands
推荐引用方式 GB/T 7714	Brisbare-Roch, Catherine,Dingemanse, Jasper,Koberstein, Ralf,et al. Promotion of sleep by targeting the orexin system in rats, dogs and humans[J]. NATURE MEDICINE,2007,13(2):150-155.
APA	Brisbare-Roch, Catherine.,Dingemanse, Jasper.,Koberstein, Ralf.,Hoever, Petra.,Aissaoui, Hamed.,...&Jenck, Francois.(2007).Promotion of sleep by targeting the orexin system in rats, dogs and humans.NATURE MEDICINE,13(2),150-155.
MLA	Brisbare-Roch, Catherine,et al."Promotion of sleep by targeting the orexin system in rats, dogs and humans".NATURE MEDICINE 13.2(2007):150-155.