The hypocretin/orexin ligand-receptor system: implications for sleep and sleep disorders

Trends Neurosci. 2000 Aug;23(8):359-65. doi: 10.1016/s0166-2236(00)01594-0.


The molecules originally described as the hypocretins and subsequently as the orexins were initially implicated in the control of food intake. Recent observations implicate this newly-described neurotransmitter system in the sleep disorder narcolepsy and, potentially, in the regulation of normal sleep processes. This article reviews the research that led to the isolation of the hypocretin/orexin peptides, their receptors and the activity of these molecules as we currently understand them. A model is proposed in which the cells that make these peptides might be involved in arousal state control.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Brain Chemistry / physiology*
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins*
  • Ligands
  • Molecular Sequence Data
  • Neuropeptides / genetics*
  • Neuropeptides / metabolism
  • Neurotransmitter Agents / genetics*
  • Neurotransmitter Agents / metabolism
  • Orexins
  • Sequence Homology, Amino Acid
  • Sleep / physiology*
  • Sleep Wake Disorders / physiopathology*


  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • Ligands
  • Neuropeptides
  • Neurotransmitter Agents
  • Orexins