Article
Chemistry, Multidisciplinary
Pilar Marcos, Rafael Covenas
Summary: Understanding the dysregulation of hypothalamic neuropeptides is crucial in studying feeding behavior and obesity. Current pharmacological strategies for obesity treatment are ineffective, highlighting the need for new therapeutic approaches. This review focuses on the involvement of the orexinergic system in feeding behavior, discussing animal models, human studies, and the connection to other substances. Promising research on orexinergic signaling pathways, heterogeneity of hypothalamic orexinergic neurons, receptor-receptor interaction, and sex differences are highlighted. The development of combination therapies and more specific orexin receptor antagonists is important for successful anti-obesity treatments.
APPLIED SCIENCES-BASEL
(2022)
Article
Biochemistry & Molecular Biology
Konstantina Vraka, Dimitrios Mytilinaios, Andreas P. Katsenos, Anastasios Serbis, Stavros Baloyiannis, Stefanos Bellos, Yannis V. Simos, Nikolaos P. Tzavellas, Spyridon Konitsiotis, Patra Vezyraki, Dimitrios Peschos, Konstantinos I. Tsamis
Summary: This study provides information about the distribution of OX1R in the human hypothalamus. OX1R is mainly found in the lateral hypothalamic area, the lateral preoptic nucleus, the supraoptic nucleus, the dorsomedial nucleus, the ventromedial nucleus, and the paraventricular nucleus. The majority of neurons in these areas (over 80%) express OX1R, with particularly high expression in the lateral tuberal nucleus (over 95% of neurons). These results reveal the distribution of OX1R at the cellular level and discuss its regulatory role in the hypothalamus.
Review
Biochemistry & Molecular Biology
Wojciech Ziemichod, Karolina Grabowska, Antonina Kurowska, Grazyna Biala
Summary: This article provides a comprehensive review of daridorexant, including its pharmacodynamics, animal and human research, pharmacokinetics, and safety. Daridorexant is considered a safe hypnotic drug with potential therapeutic effects for insomnia.
Article
Neurosciences
Joseph S. Lonstein, Katrina Linning-Duffy, Yuping Tang, Anna Moody, Lily Yan
Summary: The study showed that daytime light intensity can alter the central orexin system of both male and female grass rats, sometimes in a sex-specific manner, providing insights into how daytime light intensity impacts functions regulated by orexin.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2021)
Article
Pharmacology & Pharmacy
Asmaa Elhosainy, Haruka Suzuki-Abe, Mahesh K. Kaushik, Staci J. Kim, Tsuyoshi Saitoh, Yukiko Ishikawa, Noriko Hotta-Hirashima, Chika Miyoshi, Hiromasa Funato, Masashi Yanagisawa
Summary: Idiopathic hypersomnia (IH) is a chronic neurologic disorder characterized by long night-time sleep, daytime sleepiness, long non-refreshing naps, and sleep drunkenness. In this study, an animal model for IH was validated using a mouse version of multiple sleep latency test (MSLT) and wake EEG delta power analysis. The Sleepy mutant mouse showed shorter sleep latency and lower decay of wake EEG delta density, suggesting face validity as an IH model. Additionally, the effect of orexin-A and the orexin receptor 2-selective agonist YNT-185 on sleepiness symptoms in the Sleepy mouse was investigated, showing potential for orexin agonists as treatments for hypersomnolence.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Neurosciences
Dexin Zhang, Ying Cui, Manman Zhao, Xuecheng Zheng, Chunyan Li, Jingbo Wei, Kaijie Wang, Jianzhong Cui
Summary: This study demonstrates that OXA suppresses autophagy via the OXR1-mediated ERK/mTOR signaling pathway to exert neuroprotective effects, and it might provide a novel therapeutic approach in patients suffering from ICH.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Review
Clinical Neurology
Maria P. Mogavero, Alessandro Silvani, Giuseppe Lanza, Lourdes M. DelRosso, Luigi Ferini-Strambi, Raffaele Ferri
Summary: After describing orexins and their roles in sleep and medical disorders, the article discusses the clinical evidence on the effects of DORAs and SORAs on insomnia to provide recommendations for further assessment in personalized and precision medicine. Trials with orexin receptor antagonists have shown potential as a valid therapeutic option for insomnia in various medical conditions, but more studies are needed to determine the most suitable options for different patient populations.
NATURE AND SCIENCE OF SLEEP
(2023)
Article
Pharmacology & Pharmacy
Francisco J. Flores-Ramirez, Florence P. Varodayan, Reesha R. Patel, Jessica M. Illenberger, Francesca Di Ottavio, Marisa Roberto, Remi Martin-Fardon
Summary: Chronic alcohol use dysregulates stress responsivity, making individuals vulnerable to relapse. This study found that the OX1/2 receptor in the infralimbic cortex plays a significant role in stress-induced reinstatement of alcohol-seeking behavior. Using the OX1/2 antagonist TCS 1102 can prevent reinstatement in alcohol-dependent animals.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Review
Neurosciences
Natasha C. Dale, Daniel Hoyer, Laura H. Jacobson, Kevin D. G. Pfleger, Elizabeth K. M. Johnstone
Summary: The orexin system consists of two G protein-coupled receptors, OX1 and OX2 receptors, along with two endogenous agonists. Orexin receptor coupling is diverse and can vary depending on tissue, cell, and context. Ligands, receptor-protein interactions, and cellular environment play important roles in the G protein coupling profiles of the orexin receptors. This has implications for understanding the function of the orexin system and developing drugs targeting it.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Pharmacology & Pharmacy
Anthony Markham
Summary: Daridorexant, an orally administered dual orexin receptor antagonist, has been approved in the USA for the treatment of insomnia based on the results of pivotal phase III trials.
Editorial Material
Neurosciences
Jacqueline B. Mehr, Michelle M. Bilotti, Morgan H. James
Summary: This article discusses how the hypothalamic orexin system is now linked with motivated behavior and becomes overactive in addicted states, offering potential therapeutic opportunities for substance use disorders based on normalizing orexin function.
TRENDS IN NEUROSCIENCES
(2021)
Article
Chemistry, Medicinal
Keita Iio, Tsuyoshi Saitoh, Ryuichiro Ohshita, Tsubasa Hino, Mao Amezawa, Yoshiaki Takayama, Yasuyuki Nagumo, Naoshi Yamamoto, Noriki Kutsumura, Yoko Irukayama-Tomobe, Yukiko Ishikawa, Ryuji Tanimura, Masashi Yanagisawa, Hiroshi Nagase
Summary: A novel series of 1-amino-tetralin derivatives were designed and synthesized, and the introduction of a N-methyl-(3-methoxyphenyl)acetamide unit significantly enhanced the agonist potency. The results showed that the stereochemistry played a significant role in the selectivity and agonist activity of the orexin receptors. These findings provide important information for the development of OX1R selective agonists.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Cell Biology
Andrew S. Huhn, Patrick H. Finan, Charlene E. Gamaldo, Alexis S. Hammond, Annie Umbricht, Cecilia L. Bergeria, Eric C. Strain, Kelly E. Dunn
Summary: This study examined the use of a dual-orexin receptor antagonist in opioid withdrawal and found that it may have potential benefits for improving sleep and withdrawal outcomes.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Medicine, Research & Experimental
Fateme Khodabande, Esmaeil Akbari, Motahareh Rouhi Ardeshiri
Summary: The orexin 1 receptors in the dorsal raphe nucleus play a significant role in the consolidation of spatial reference memory in rats, while the orexin 2 receptors do not have an effect.
Article
Psychiatry
Giorgio Bergamini, Preciosa Coloma, Helene Massinet, Michel Alexander Steiner
Summary: Neuropsychiatric symptoms (NPS) commonly affect people with dementia, regardless of disease stage or etiology. These symptoms lead to disability and reduced quality of life for both patients and their caregivers. The orexin neuropeptide system plays a crucial role in modulating arousal and behavior, and may be relevant for the expression of NPS in dementia patients.
FRONTIERS IN PSYCHIATRY
(2022)