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)
Review
Clinical Neurology
Maria Paola Mogavero, Lourdes M. DelRosso, Francesco Fanfulla, Oliviero Bruni, Raffaele Ferri
Summary: There is a bidirectional connection between sleep and cancer, but the specific associations between individual sleep disorders and particular tumors are still unclear. Accurately assessing sleep disorders in cancer patients is essential for improving patient health, survival, response to therapy, quality of life, and reducing comorbidities/complications. Recent scientific evidence suggests that knowledge and management of sleep disorders can provide interesting therapeutic perspectives for cancer treatment.
SLEEP MEDICINE REVIEWS
(2021)
Article
Endocrinology & Metabolism
Mohammad Sheibani, Maryam Shayan, Mina Khalilzadeh, Mehdi Ghasemi, Ahmad Reza Dehpour
Summary: The correlation between sleep and epilepsy has been debated among scientists for many years. Sleep is a recurring state of mind and body that involves alternations in brain electrical activities. Sleep disorders are associated with epilepsy, which affects the origin, suppression, and spread of seizures. Orexin, a neuropeptide involved in wakefulness, has bidirectional effects on sleep and epilepsy. Understanding the relationship between sleep, epilepsy, and orexin is important for developing potential therapeutic strategies.
Article
Medicine, Research & Experimental
Qianwen Wang, Xi Wang, Chun Yang, Long Wang
Summary: The review on the comorbidity of sleep disorders and cardiovascular diseases emphasizes the critical roles of inflammation, sympathetic activation, and endothelial dysfunction in the relationship between the two. In addition to existing mechanisms, novel potential mechanisms such as gut microbiota, orexin, and extracellular vesicles are summarized, providing a theoretical basis for further research and clinical investigations.
Review
Nutrition & Dietetics
Maria P. Mogavero, Justyna Godos, Giuseppe Grosso, Filippo Caraci, Raffaele Ferri
Summary: This review focuses on the relationship between sleep-wake regulation and appetite control, emphasizing the inhibitory effect of OREXIN, a neurotransmitter, on REM sleep. It further examines the intricate relationship between OREXIN, REM sleep, and appetite regulation, shedding light on their interconnected nature in both physiological conditions and diseases. Understanding this complex relationship is crucial for unraveling the mechanisms underlying sleep-wake patterns and metabolic control, and for developing novel therapeutic approaches to sleep disorders and metabolic conditions associated with OREXIN dysregulation.
Article
Pharmacology & Pharmacy
Marie Pardon, Pieter Claes, Sarah Druwe, Murielle Martini, Aleksandra Siekierska, Christel Menet, Peter A. M. de Witte, Danielle Copmans
Summary: New pharmacological approaches are being developed to treat sleep disorders with fewer side effects. Zebrafish larvae are being used as a model to evaluate the functionality of small molecule OX2R agonists and antagonists and their effects on behavior, to discover novel compounds for the treatment of sleep disorders.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Hiroshi Tsuneki, Masanori Sugiyama, Kiyofumi Sato, Hisakatsu Ito, Sanaka Nagai, Kanta Kon, Tsutomu Wada, Nao Kobayashi, Takuya Okada, Naoki Toyooka, Masashi Kawasaki, Toshihiro Ito, Ryota Otsubo, Daisuke Okuzaki, Teruhito Yasui, Toshiyasu Sasaoka
Summary: The drug lemborexant, used to treat insomnia, has been found to have a positive effect on sleep and glucose metabolism in individuals with type 2 diabetes. In experiments, lemborexant increased sleep duration and improved glucose tolerance in db/db mice. This improvement did not affect body weight or insulin secretion.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Review
Clinical Neurology
Chiara Berteotti, Carmen Calvello, Claudio Liguori
Summary: Epilepsy is a common neurological disorder that affects patients of all ages and is associated with reduced quality of life and comorbidities. Sleep impairment is frequently observed in epilepsy patients, and the relationship between sleep and epilepsy is bidirectional. The orexin system, which plays a role in controlling the sleep-wake cycle, may be affected in epilepsy patients. Clinical studies have shown inconsistent results due to different methodologies in quantifying orexin levels. Dual orexin receptor antagonists (DORAs) have been suggested as a potential treatment for sleep impairment and insomnia in epilepsy patients.
Article
Psychology, Developmental
Aaron D. Besterman, Shafali S. Jeste
Summary: Insomnia is a common and difficult-to-treat comorbidity in children with neurodevelopmental disorders. The use of dual orexin receptor antagonists (DORAs) as a treatment option for insomnia in these children has little safety or efficacy data. Research shows diverse responses to DORA suvorexant, with some patients experiencing significant improvement in sleep while others had mild or no benefit.
EUROPEAN CHILD & ADOLESCENT PSYCHIATRY
(2023)
Article
Multidisciplinary Sciences
Shi-Bin Li, Valentina Martinez Damonte, Chong Chen, Gordon X. Wang, Justus M. Kebschull, Hiroshi Yamaguchi, Wen-Jie Bian, Carolin Purmann, Reenal Pattni, Alexander Eckehart Urban, Philippe Mourrain, Julie A. Kauer, Gregory Scherrer, Luis de Lecea
Summary: Sleep quality declines with age and this study identified hyperexcitable hypocretin/orexin (Hcrt/OX) neurons as drivers of sleep fragmentation during aging. Activation of Hcrt neurons increased wakefulness and aged Hcrt neurons showed hyperexcitability and impaired M-current. Disruption of Kcnq2/3 genes in young mice led to sleep destabilization resembling aging-associated sleep fragmentation.
Article
Pharmacology & Pharmacy
Ryan J. Keenan, Heather Daykin, Jiahui Chu, Linda Cornthwaite-Duncan, Giancarlo Allocca, Daniel Hoyer, Laura H. Jacobson
Summary: This study investigates the effects of sleep-promoting compounds in transgenic mouse models of tauopathy and finds that these compounds can effectively improve sleep disturbances. The results also suggest that there may be gender differences in the response to hypnotics, which could have implications for the treatment of neurodegenerative disorders in humans.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
William T. Schneider, Szilvia Vas, Alister U. Nicol, A. Jennifer Morton
Summary: Research showed that in sheep with HD, transitions into wake were more sudden and accompanied by less reduction in slow wave power compared to normal sheep, indicating impaired readiness for waking. These abnormal dynamics of sleep transitions may potentially serve as an early biomarker for HD and could be applied to studying transition dynamics in other sleep disorders as well.
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
Behavioral Sciences
Lu Wang, Yundan Pan, Chunyan Ye, Lizhe Guo, Sumei Luo, Sisi Dai, Na Chen, E. Wang
Summary: Orexin receptor antagonists can be widely used in adults and the elderly, with both short-term and long-term use being effective for primary insomnia. H1 antagonists are more effective in adults than in the elderly. Although benzodiazepines have a more obvious effect on sleep maintenance, it is best to reduce their use due to their side effects, especially for the elderly. As a food supplement, melatonin has little effect on adults, but it still has a certain effect on the elderly.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2021)
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.
Article
Behavioral Sciences
Darrell Eacret, Laura A. Grafe, Jane Dobkin, Anthony L. Gotter, John J. Renger, Christopher J. Winrow, Seema Bhatnagar
BEHAVIOURAL BRAIN RESEARCH
(2019)
Article
Geriatrics & Gerontology
Paige E. Cramer, Renee C. Gentzel, Keith Q. Tanis, Joshua Vardigan, Yi Wang, Brett Connolly, Philip Manfre, Kenneth Lodge, John J. Renger, Celina Zerbinatti, Jason M. Uslaner
NEUROBIOLOGY OF AGING
(2018)
Article
Multidisciplinary Sciences
Joseph R. Scarpa, Peng Jiang, Vance D. Gao, Karrie Fitzpatrick, Joshua Millstein, Christopher Olker, Anthony Gotter, Christopher J. Winrow, John J. Renger, Andrew Kasarskis, Fred W. Turek, Martha H. Vitaterna
Article
Immunology
Susana S. Correia, Guang Liu, Sarah Jacobson, Sylvie G. Bernier, Jenny V. Tobin, Chad D. Schwartzkopf, Emily Atwater, Elisabeth Lonie, Sam Rivers, Andrew Carvalho, Peter Germano, Kim Tang, Rajesh R. Iyengar, Mark G. Currie, John R. Hadcock, Christopher J. Winrow, Juli E. Jones
Summary: CYR119, a CNS-penetrant sGC stimulator, attenuates neuroinflammation by increasing cGMP production and shows neuroprotective effects in vivo models.
JOURNAL OF NEUROINFLAMMATION
(2021)
Article
Pharmacology & Pharmacy
Susana S. Correia, Rajesh R. Iyengar, Peter Germano, Kim Tang, Sylvie G. Bernier, Chad D. Schwartzkopf, Jenny Tobin, Thomas W. -H. Lee, Guang Liu, Sarah Jacobson, Andrew Carvalho, Glen R. Rennie, Joon Jung, Paul A. Renhowe, Elisabeth Lonie, Christopher J. Winrow, John R. Hadcock, Juli E. Jones, Mark G. Currie
Summary: Effective treatments for neurodegenerative diseases are urgently needed as the global population ages. CY6463, a brain-penetrant sGC stimulator, has shown promise in preclinical models by improving neuronal activity, mediating neuroprotection, and enhancing cognitive performance.
FRONTIERS IN PHARMACOLOGY
(2021)
Letter
Genetics & Heredity
Katy Phelan, Luigi Boccuto, Craig M. Powell, Tobias M. Boeckers, Conny van Ravenswaaij-Arts, R. Curtis Rogers, Carlo Sala, Chiara Verpelli, Audrey Thurm, William E. Bennett, Christopher J. Winrow, Sheldon R. Garrison, Roberto Toro, Thomas Bourgeron
Summary: Phelan-McDermid syndrome, initially known as 22q13 deletion syndrome, is now recognized to be associated with SHANK3 gene. To reduce confusion, a simple classification system has been proposed, dividing PMS into PMS-SHANK3 related and PMS-SHANK3 unrelated cases.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Meeting Abstract
Medicine, Research & Experimental
Emmanuel S. Buys, Susana S. Correia, Guang Liu, Joon Jung, John R. Hadcock, Peter Germano, Christopher J. Winrow, Juli E. Jones
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Meeting Abstract
Medicine, Research & Experimental
Christopher J. Winrow
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Meeting Abstract
Neurosciences
Stacey Versavel, Rachel Gurrell, Ih Chang, Ann Dandurand, Sridhar Duvvuri, Amy Giugliano, Gina Pastino, Theresa Pham, Gabriel Jacobs, Koshar Safai Pour, Rob Zuiker, Raymond Sanchez, John Renger
NEUROPSYCHOPHARMACOLOGY
(2022)
Article
Medicine, General & Internal
John H. Krystal, John M. Kane, Christoph U. Correll, David P. Walling, Matthew Leoni, Sridhar Duvvuri, Shrinal Patel, Ih Chang, Philip Iredale, Lillian Frohlich, Stacey Versavel, Pamela Perry, Raymond Sanchez, John Renger
Summary: The trial involved two parts with a total of 167 schizophrenia patients. The results showed that emraclidine once-daily treatment had good safety and tolerability, demonstrating potential for further investigation as a treatment for schizophrenia.
Meeting Abstract
Neurosciences
Sridhar Duvvuri, Philip Iredale, Matthew Leoni, Vasily Belov, Nicolas Guehl, Sung-Hyun Moon, Maeva Dhaynaut, Peter Rice, Daniel Yokell, Georges El Fakhri, Marc Normandin, John Renger
NEUROPSYCHOPHARMACOLOGY
(2021)
Meeting Abstract
Neurosciences
John Krystal, John Kane, Christoph Correll, David Walling, Matthew Leoni, Sridhar Duvvuri, Ih Chang, Philip Iredale, Stacey Versavel, Lillian Frohlich, Shrinal PatelPamela Perry, Raymond Sanchez, John Renger
NEUROPSYCHOPHARMACOLOGY
(2021)
Meeting Abstract
Endocrinology & Metabolism
Vasily Belov, Nicolas J. Guehl, Sridhar Duvvuri, Philip Iredale, Sung-Hyun Moon, Maeva Dhaynaut, Peter A. Rice, Daniel L. Yokell, John Renger, Georges El Fakhri, Marc D. Normandin
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2021)
Article
Medicine, Research & Experimental
Rahul Sasane, Amy Bartels, Michelle Field, Maria I. Sierra, Sridhar Duvvuri, David L. Gray, Sokhom S. Pin, John J. Renger, David J. Stone
Summary: The study found that tamsulosin users had a significantly higher incidence of Parkinson's disease compared to terazosin/alfuzosin/doxazosin users and matched controls. There was no significant difference in Parkinson's disease risk between terazosin/alfuzosin/doxazosin users and matched controls. These results suggest that tamsulosin may exacerbate Parkinson's disease progression.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
