Orexin in sleep, addiction and more: Is the perfect insomnia drug at hand?

@article{Hoyer2013OrexinIS,
  title={Orexin in sleep, addiction and more: Is the perfect insomnia drug at hand?},
  author={Daniel Hoyer and Laura H. Jacobson},
  journal={Neuropeptides},
  year={2013},
  volume={47},
  pages={477-488}
}

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The hypocretin/orexin system as a target for excessive motivation in alcohol use disorders
TLDR
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TLDR
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This study involved healthy rodent, canine and human subjects, in whom a dual OX1/OX2 receptor antagonist elicited somnolence and sleep, but not cataplexy, when administered as a single oral dose during the active period of the circadian cycle.
Differential Roles of Orexin Receptor-1 and -2 in the Regulation of Non-REM and REM Sleep
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Results suggest that although the OX2R-mediated pathway has a pivotal role in the promotion of wakefulness, OX1R also plays additional roles in promoting arousal, and each orexin receptor subtype plays differential roles in gating NREM and REM sleep through distinct neuronal pathways.
To eat or to sleep? Orexin in the regulation of feeding and wakefulness.
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These findings suggest that the orexin neuropeptide system plays a significant role in feeding and sleep-wakefulness regulation, possibly by coordinating the complex behavioral and physiologic responses of these complementary homeostatic functions.
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Dosed orally Suvorexant significantly and dose-dependently reduced locomotor activity and promoted sleep in rats, dogs, and rhesus monkeys, highlighting a unique opportunity to develop dual orexin antagonists as a novel therapy for insomnia.
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In rats, dogs and humans, somnolence is induced by pharmacological blockade of both orexin OX1 and OX2 receptors, and this results open new perspectives for investigating the role of endogenous orexins in sleep-wake regulation.
Genetic Ablation of Orexin Neurons in Mice Results in Narcolepsy, Hypophagia, and Obesity
Arousal effect of orexin A depends on activation of the histaminergic system
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TLDR
Findings strongly indicate that the arousal effect of orexin A depends on the activation of histaminergic neurotransmission mediated by H1R.
Orexin peptides prevent cataplexy and improve wakefulness in an orexin neuron-ablated model of narcolepsy in mice.
TLDR
Results indicate that orexin neuron-ablated mice retain the ability to respond to orexIn neuropeptides and that a temporally regulated and spatially targeted secretion of orexins is not necessary to prevent narcoleptic symptoms.
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