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Link to original content: https://pubmed.ncbi.nlm.nih.gov/17259994
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Comparative Study
. 2007 Feb;13(2):150-5.
doi: 10.1038/nm1544. Epub 2007 Jan 28.

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

Catherine Brisbare-Roch  1 , Jasper Dingemanse, Ralf Koberstein, Petra Hoever, Hamed Aissaoui, Susan Flores, Celia Mueller, Oliver Nayler, Joop van Gerven, Sanne L de Haas, Patrick Hess, Changbin Qiu, Stephan Buchmann, Michael Scherz, Thomas Weller, Walter Fischli, Martine Clozel, François Jenck
Affiliations
Comparative Study

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

Catherine Brisbare-Roch et al. Nat Med. 2007 Feb.

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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