An Update on Dual Orexin Receptor Antagonists and Their Potential Role in Insomnia Therapeutics.
Reads0
Chats0
TLDR
Targeting the orexin receptor system for treatment of insomnia offers an additional and alternative pharmacological approach to more common gamma aminobutyric acid agonist sedative hypnotic treatment.Abstract:
Study Objectives:Current pharmacological options for the treatment of insomnia insufficiently meet the needs of all insomnia patients. Approved treatments are not consistently effective in improvin...read more
Citations
More filters
Journal ArticleDOI
Clinical drug development for dementia with Lewy bodies: past and present
Garam Lee,Jeffrey L. Cummings,Jeffrey L. Cummings,Boris Decourt,James B. Leverenz,Marwan N. Sabbagh +5 more
TL;DR: An overview of the DLB drug development landscape and the current treatment strategies is provided and new biomarker strategies are necessary to improve diagnostic capabilities and trial designs, and novel drug targets should be identified to develop DLB specific disease-modifying therapies.
Journal ArticleDOI
Differential Roles of Each Orexin Receptor Signaling in Obesity.
Miyo Kakizaki,Yousuke Tsuneoka,Kenkichi Takase,Staci Jakyong Kim,Jinhwan Choi,Aya Ikkyu,Manabu Abe,Kenji Sakimura,Masashi Yanagisawa,Masashi Yanagisawa,Hiromasa Funato,Hiromasa Funato +11 more
TL;DR: Each orexin receptor signaling has a unique role in energy metabolism, and Orexin neurons are involved in the interactive effect of diet and exercise on body weight gain.
Journal ArticleDOI
Hypocretins (orexins): The ultimate translational neuropeptides
TL;DR: Circuit neuroscience findings suggest that the Hcrt system is a hub that integrates diverse inputs modulating arousal and conveys this information to multiple output regions and highlights the potential of the HCrt system as a therapeutic target for a number of disorders.
Journal ArticleDOI
Cyclic tailor-made amino acids in the design of modern pharmaceuticals
Jiang Liu,Jianlin Han,Kunisuke Izawa,Tatsunori Sato,Sarah White,Nicholas A. Meanwell,Vadim A. Soloshonok,Vadim A. Soloshonok +7 more
TL;DR: The present review article highlights 34 compounds, all of which are derived from cyclic AAs, representing recently-approved, small-molecule pharmaceuticals as well as promising drug candidates currently in various phases of clinical study.
Journal ArticleDOI
Sleep dysregulation in binge eating disorder and "food addiction": the orexin (hypocretin) system as a potential neurobiological link.
Jacqueline B. Mehr,Jacqueline B. Mehr,Deborah Mitchison,Deborah Mitchison,Hannah E. Bowrey,Hannah E. Bowrey,Morgan H. James,Morgan H. James +7 more
TL;DR: The authors identified the orexin (hypocretin) system as a potential neurobiological link between compulsive eating and sleep dysregulation in BED, and provided a comprehensive update on the evidence linking this system to these processes.
References
More filters
Journal ArticleDOI
Orexins and Orexin Receptors: A Family of Hypothalamic Neuropeptides and G Protein-Coupled Receptors that Regulate Feeding Behavior
Takeshi Sakurai,Akira Amemiya,Makoto Ishii,Ichiyo Matsuzaki,Richard M. Chemelli,Hirokazu Tanaka,S. Clay Williams,James A. Richardson,Gerald P. Kozlowski,Shelagh Wilson,Jonathan R.S. Arch,Robin E. Buckingham,Andrea C. Haynes,Steven A. Carr,Roland S. Annan,Dean E. McNulty,Wu Schyong Liu,Jonathan A. Terrett,Nabil Elshourbagy,Derk J. Bergsma,Masashi Yanagisawa +20 more
TL;DR: Two novel neuropeptides are identified, both derived from the same precursor by proteolytic processing, that bind and activate two closely related (previously) orphan G protein-coupled receptors in the hypothalamus of rats.
Journal ArticleDOI
The hypocretins: Hypothalamus-specific peptides with neuroexcitatory activity
L de Lecea,Thomas S. Kilduff,Christelle Peyron,Xiao-Bing Gao,Pamela E. Foye,Patria E. Danielson,C. Fukuhara,Elena Battenberg,Vigdis T. Gautvik,Frederick S. Bartlett,Wayne N. Frankel,A. N. van den Pol,Floyd E. Bloom,Kaare M. Gautvik,J G Sutcliffe +14 more
TL;DR: A hypothalamus-specific mRNA is described that encodes preprohypocretin, the putative precursor of a pair of peptides that share substantial amino acid identities with the gut hormone secretin, suggesting that the hypocretins function within the CNS as neurotransmitters.
Journal ArticleDOI
Sleep Drives Metabolite Clearance From the Adult Brain
Lulu Xie,Hongyi Kang,Qiwu Xu,Michael Chen,Yonghong Liao,Meenakshisundaram Thiyagarajan,John O’Donnell,Daniel J. Christensen,Charles Nicholson,Jeffrey J. Iliff,Takahiro Takano,Rashid Deane +11 more
TL;DR: It is reported that sleep has a critical function in ensuring metabolic homeostasis and convective fluxes of interstitial fluid increased the rate of β-amyloid clearance during sleep, suggesting the restorative function of sleep may be a consequence of the enhanced removal of potentially neurotoxic waste products that accumulate in the awake central nervous system.
Journal ArticleDOI
Neurons Containing Hypocretin (Orexin) Project to Multiple Neuronal Systems
Christelle Peyron,Devin K. Tighe,Anthony N. van den Pol,Anthony N. van den Pol,Luis de Lecea,H. Craig Heller,J. Gregor Sutcliffe,Thomas S. Kilduff +7 more
TL;DR: The results of this immunohistochemical study suggest that hypocretins are likely to have a role in physiological functions in addition to food intake such as regulation of blood pressure, the neuroendocrine system, body temperature, and the sleep–waking cycle.
Journal ArticleDOI
Narcolepsy in orexin knockout mice: Molecular genetics of sleep regulation
Richard M. Chemelli,Jon T. Willie,Christopher M. Sinton,Joel K. Elmquist,Thomas E. Scammell,Charlotte E. Lee,James A. Richardson,S. Clay Williams,Yumei Xiong,Yaz Y. Kisanuki,Thomas Fitch,Masamitsu Nakazato,Robert E. Hammer,Clifford B. Saper,Masashi Yanagisawa +14 more
TL;DR: It is proposed that orexin regulates sleep/wakefulness states, and that Orexin knockout mice are a model of human narcolepsy, a disorder characterized primarily by rapid eye movement (REM) sleep dysregulation.
Related Papers (5)
Orexins and Orexin Receptors: A Family of Hypothalamic Neuropeptides and G Protein-Coupled Receptors that Regulate Feeding Behavior
Takeshi Sakurai,Akira Amemiya,Makoto Ishii,Ichiyo Matsuzaki,Richard M. Chemelli,Hirokazu Tanaka,S. Clay Williams,James A. Richardson,Gerald P. Kozlowski,Shelagh Wilson,Jonathan R.S. Arch,Robin E. Buckingham,Andrea C. Haynes,Steven A. Carr,Roland S. Annan,Dean E. McNulty,Wu Schyong Liu,Jonathan A. Terrett,Nabil Elshourbagy,Derk J. Bergsma,Masashi Yanagisawa +20 more