Hypocretin/orexin receptor pharmacology and sleep phases
| Autor: | Thomas S. Kilduff, Ryan K Tisdale, Yu Sun |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Sleep Wake Disorders
Neuropeptide Disorders of Excessive Somnolence Article Arousal Orexin Receptors Sleep Initiation and Maintenance Disorders mental disorders medicine Animals Humans Wakefulness Receptor Sleep disorder Orexins business.industry digestive oral and skin physiology medicine.disease Orexin receptor Orexin nervous system Excitatory postsynaptic potential Orexin Receptor Antagonists business Sleep Neuroscience psychological phenomena and processes Narcolepsy |
| Zdroj: | Front Neurol Neurosci |
| Popis: | The hypocretins/orexins are two excitatory neuropeptides, alternately called HCRT1 or orexin-A and HCRT2 or orexin-B, that are the endogenous ligands for two G protein-coupled receptors, HCRTR1/OX(1)R and HCRTR2/OX(2)R. Shortly after the discovery of this system, degeneration of hypocretin/orexin-producing neurons was implicated in the etiology of the sleep disorder narcolepsy. The involvement of this system in a disorder characterized by the loss of control over arousal state boundaries also suggested its role as a critical component of endogenous sleep/wake regulatory circuitry. The broad projections of the hypocretin/orexin-producing neurons, along with differential expression of the two receptors in the projection fields of these neurons, suggest distinct roles for these receptors. While HCRTR1/OX(1)R is associated with regulation of motivation, reward, and autonomic functions, HCRTR2/OX(2)R is strongly linked to sleep/wake control. The association of hypocretin/orexin with these physiological processes has led to intense interest in the therapeutic potential of compounds targeting these receptors. Agonists and antagonists for the hypocretin/orexin receptors have shown potential for the treatment of disorders of excessive daytime somnolence and nocturnal hyperarousal, respectively, with the first two antagonists approved by the U.S. Food and Drug Administration (FDA) in 2014 and 2019 for the treatment of insomnia. These and related compounds have also been useful tools to advance hypocretin/orexin neurobiology. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|