Promotion of sleep by targeting the orexin system in rats, dogs and humans.
Nat Med
; 13(2): 150-5, 2007 Feb.
Article
em En
| MEDLINE
| ID: mdl-17259994
ABSTRACT
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 OX(1) and OX(2) 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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sono REM
/
Neuropeptídeos
/
Transdução de Sinais
/
Receptores de Neuropeptídeos
/
Tetra-Hidroisoquinolinas
/
Receptores Acoplados a Proteínas G
/
Peptídeos e Proteínas de Sinalização Intracelular
/
Hipotálamo Posterior
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Isoquinolinas
/
Acetamidas
Limite:
Animals
/
Female
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Humans
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Male
Idioma:
En
Revista:
Nat Med
Assunto da revista:
BIOLOGIA MOLECULAR
/
MEDICINA
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Suíça