The present and future of synthetic orexin receptor agonists.
Analgegic
Narcolepsy
OX1R agonist
OX2R agonist
Orexin A
Orexin B
Reinforcing
Journal
Peptides
ISSN: 1873-5169
Titre abrégé: Peptides
Pays: United States
ID NLM: 8008690
Informations de publication
Date de publication:
09 2023
09 2023
Historique:
received:
03
05
2023
revised:
16
06
2023
accepted:
02
07
2023
medline:
31
7
2023
pubmed:
9
7
2023
entrez:
8
7
2023
Statut:
ppublish
Résumé
The neuropeptide orexin/hypocretin plays a crucial role in various physiological processes, including the regulation of sleep/wakefulness, appetite, emotion and the reward system. Dysregulation of orexin signaling has been implicated in hypersomnia, especially in narcolepsy, which is a chronic neurological disorder characterized by excessive daytime sleepiness (EDS), sudden loss of muscle tone while awake (cataplexy), sleep paralysis, and hallucinations. Small-molecule orexin receptor agonists have emerged as promising therapeutics for these disorders, and significant progress has been made in this field in the past decade. This review summarizes recent advances in the design and synthesis of orexin receptor agonists, with a focus on peptidic and small-molecule OX2R-selective, dual, and OX1R-selective agonists. The review discusses the key structural features and pharmacological properties of these agonists, as well as their potential therapeutic applications.
Identifiants
pubmed: 37422012
pii: S0196-9781(23)00114-6
doi: 10.1016/j.peptides.2023.171051
pii:
doi:
Substances chimiques
Orexins
0
Orexin Receptors
0
Neuropeptides
0
Types de publication
Review
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
171051Informations de copyright
Copyright © 2023 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors have no conflicts of interest directly relevant to the content of this article.