Orexin receptor

The orexin receptor (also referred to as the hypocretin receptor) is a G-protein-coupled receptor that binds the neuropeptide orexin. There are two variants, OX₁ and OX₂, each encoded by a different gene (HCRTR1, HCRTR2).

Both orexin receptors exhibit a similar pharmacology - the 2 orexin peptides, orexin-A and orexin-B, bind to both receptors and, in each case, agonist binding results in an increase in intracellular calcium levels. However, orexin-B shows a 10-fold selectivity for orexin receptor type 2, whilst orexin-A is equipotent at both receptors.

Several orexin receptor antagonists are in development for potential use in sleep disorders. Only the crystal structure of OX2 is known.

Selective ligands

Several drugs acting on the orexin system are under development, either orexin agonists for the treatment of conditions such as narcolepsy, or orexin antagonists for insomnia. No non-peptide agonists are yet available, although synthetic Orexin-A polypeptide has been made available as a nasal spray and tested on monkeys. Several non-peptide antagonists are in development however; SB-649,868 by GlaxoSmithKline for sleep disorders is a non-selective orexin receptor antagonist. Another dual orexin antagonist, almorexant (ACT-078573) by Actelion, was abandoned because of side effects. A third entry is Merck's suvorexant (Belsomra), which has recently been approved for use. A new antagonist compound, ACT-462206, was recently studied in humans.

Hypocretin (orexin) receptor 2

Orexin receptor type 2 (Ox2R or OX₂), also known as hypocretin receptor type 2, is a protein that in humans is encoded by the HCRTR2 gene.

Function

OX₂ is a G-protein coupled receptor expressed exclusively in the brain. It has 64% identity with OX₁. OX₂ binds both orexin A and orexin B neuropeptides. OX₂ is involved in the central feedback mechanism that regulates feeding behaviour.

Ligands

Agonists

Antagonists

See also

Hypocretin (orexin) receptor 1

Orexin receptor type 1 (Ox1R or OX₁), also known as hypocretin receptor type 1, is a protein that in humans is encoded by the HCRTR1 gene.

Function

The orexin 1 receptor (OX₁), is a G-protein coupled receptor expressed in the hypothalamus and involved in the regulation of feeding behaviour. OX₁ selectively binds the orexin-A neuropeptide. It shares 64% identity with OX₂.

Ligands

Agonists

Antagonists

See also

References

External links

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.