Orexin Receptor Antagonists: A New Concept In CNS Disorders?

  title={Orexin Receptor Antagonists: A New Concept In CNS Disorders?},
  author={John Gatfield and Catherine Brisbare-Roch and François Jenck and Christoph Boss},
The orexin (hypocretin) system is an evolutionarily conserved neuropeptide–GPCR system functioning even in vertebrate fish. After a decade of intensive work, it appears that the orexin system plays a crucial role as homeostatic sensor of the body’s external and internal environment and regulates states of wakefulness to facilitate survival. In the brain, it acts as a central regulator of wakefulness and modulates emotional states related to, for example, stress or reward. In accordance with… 

Selective orexin receptor antagonists.

Orexin receptors: Targets and applications.

The structure of orexin receptors, their physiological role and various applications in disease states are discussed, adding a note on agonists and antagonists and finally summarizing the recent drug approvals in the field.

Orexin Receptor Antagonists

The Hypocretin/Orexin System: Implications for Drug Reward and Relapse

Based on preclinical studies, the use of selective ligands targeting hypocretin receptors could represent a new therapeutical strategy for the treatment of substance abuse disorders.

Recent trends in orexin research--2010 to 2015.

  • C. BossC. Roch
  • Biology, Psychology
    Bioorganic & medicinal chemistry letters
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Orexin receptor antagonists – a patent review (2010 to August 2014)

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  • Biology, Psychology
    Expert opinion on therapeutic patents
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The advantage of orexin antagonists, based on animal pharmacology results, is the promotion and maintenance of physiological sleep which should avoid hangover phenomena reported as side effects of approved treatments.

Truncated Orexin Peptides: Structure-Activity Relationship Studies.

The goal of this study was to further investigate the structure-activity relationships of these peptides and to identify truncated form of the orexin peptides active at OX1.



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The current knowledge on peripheral functions of orexins is focused on and possible endocrine, paracrine and neurocrine roles are discussed.

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The current understanding of the physiological roles of orexins in regulation of arousal, sleep/wake states, energy homeostasis, and reward systems is discussed.

Orexin Receptors Are Expressed in the Adrenal Medulla of the Rat.

The results of the present study provide the first evidence showing that the adrenal medulla of the rat expresses orexin receptors, and thus appears to be a target tissue for orexins, which could open a new loop in which the central and autonomous nervous system may be involved in body weight homeostasis and sleep control.

Arousal and reward: a dichotomy in orexin function

Orexin: a link between energy homeostasis and adaptive behaviour.

  • T. Sakurai
  • Biology, Psychology
    Current opinion in clinical nutrition and metabolic care
  • 2003
Orexin neurons have the requisite functional interactions with hypothalamic feeding pathways and monoaminergic-cholinergic centres in the brain stem, and regulation by nutritional factors, to suggest that they may be an important cellular link in the integration of adaptive behaviour associated with arousal and energy homeostasis.

Interactions of orexins/hypocretins with adrenocortical functions

Recent findings indicate that orexins stimulate adrenocortical steroidogenesis by augmenting transcription of selective steroidogenic enzymes and proteins such as steroidogenic acute regulatory protein.

Biomedical application of orexin/hypocretin receptor ligands in neuroscience.

Orexin/hypocretin neuropeptides are peptides discovered and published in 1998 by two independent research groups as the outcome of methodical deorphanization programs focusing on brain orphan G-protein-coupled receptors (GPCR).