Promotion of sleep by targeting the orexin system in rats, dogs and humans
Author: ["Catherine Brisbare-Roch","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"]
Publication: Nature Medicine
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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 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 GABAA 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.
Cite this article
Brisbare-Roch, C., Dingemanse, J., Koberstein, R. et al. Promotion of sleep by targeting the orexin system in rats, dogs and humans. Nat Med 13, 150–155 (2007). https://doi.org/10.1038/nm1544
