Article
Clinical Neurology
Tobias Di Marco, Thomas E. Scammell, Michael Meinel, Dalma Seboek Kinter, Alexandre N. Datta, Gary Zammit, Yves Dauvilliers
Summary: The study aimed to explore the effect of daridorexant, a dual orexin receptor antagonist, on nighttime wake bouts and their correlation with daytime functioning. Results showed that daridorexant reduced the number and duration of long wake bouts during the night compared with placebo, corresponding with improved daytime functioning.
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.
Review
Psychiatry
Habibolah Khazaie, Masoud Sadeghi, Sepideh Khazaie, Max Hirshkowitz, Amir Sharafkhaneh
Summary: The study conducted a systematic review and meta-analysis on the treatment of insomnia with suvorexant and lemborexant, showing that both drugs are effective and safe for patients with insomnia.
FRONTIERS IN PSYCHIATRY
(2022)
Article
Clinical Neurology
Mike Ufer, Debra Kelsh, Kerri A. Schoedel, Jasper Dingemanse
Summary: This study evaluated the abuse potential of daridorexant in healthy recreational sedative drug users. The results showed dose-related drug-liking effects of daridorexant, with lower effects at the highest dose and similar effects at higher doses compared to supratherapeutic doses of suvorexant and zolpidem. The safety and pharmacokinetics of daridorexant were consistent with earlier trials, with quick absorption and elimination.
Review
Neurosciences
Catherine Roch, Giorgio Bergamini, Michel A. Steiner, Martine Clozel
Summary: Dual orexin receptor antagonists (DORAs), such as daridorexant, offer a novel type of sleep medication with benefits in insomnia treatment and improvement in daytime functioning, without the risk of tolerance or physical dependence. This new DORA inhibits the wake-promoting orexin neuropeptides specifically, avoiding widespread inhibition of neuronal pathways and associated side effects typical of positive allosteric GABA-A receptor modulators.
PSYCHOPHARMACOLOGY
(2021)
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
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)
Review
Pharmacology & Pharmacy
Tao Xue, Xin Wu, Jiaxuan Li, Shujun Chen, Zilan Wang, Xin Tan, Zhong Wang, Jianguo Zhang
Summary: Systematic comparisons of FDA-approved dual orexin receptor antagonists (DORAs) revealed that suvorexant (20 mg and 40 mg) and daridorexant (10 mg and 50 mg) were most effective in reducing latency to persistent sleep (LPS). Lemborexant at 5 mg and 10 mg showed the most effectiveness in reducing subjective sleep onset time (sTSO). Overall, suvorexant, lemborexant, and daridorexant represent suitable approaches for the treatment of insomnia.
FRONTIERS IN PHARMACOLOGY
(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
Shunpei Moriya, Hitoshi Takahashi, Daiki Masukawa, Makiko Yamada, Jun Ishigooka, Katsuji Nishimura
Summary: The orexinergic system is crucial in regulating proper sleep/wake maintenance, and the dual orexin receptor antagonist (DORA) is commonly used for treating insomnia symptoms. DORA treatment significantly impacts the expression levels of monoamine-related genes in the hippocampus, contributing to the regulation of noradrenalin-related gene expression in the central nervous system.
JOURNAL OF PHARMACOLOGICAL SCIENCES
(2021)
Article
Clinical Neurology
Marie-Laure Boof, Mike Ufer, Ingo Fietze, Jean-Louis Pepin, Anne-Sophie Guern, Vincent Lemoine, Jasper Dingemanse
Summary: The study found that daridorexant can be safely used in patients with mild to moderate obstructive sleep apnea, with similar effects on respiration and sleep as placebo, but with an increase in some respiratory events.
Article
Pharmacology & Pharmacy
Daiji Kambe, Sayaka Hasegawa, Yumiko Imadera, Yoko Mano, Isao Matsushita, Yoshihiro Konno, Hiroki Ogo, Naohisa Uchimura, Makoto Uchiyama
Summary: The pharmacokinetics, pharmacodynamics and safety profile of vornorexant were investigated in healthy Japanese participants. Vornorexant was rapidly absorbed and eliminated, with a time to maximum plasma concentration of 0.5-3.0 h and elimination half-life of 1.32-3.25 h. Dose increments of vornorexant were associated with increased sleepiness-related pharmacodynamic outcome changes, but no consistent dose-related changes were observed the next morning.
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
(2023)
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)
Review
Clinical Neurology
Donghao Wang, Yongkang Tang, Yanghang Chen, Sun Zhang, Danjie Ma, Yateng Luo, Shiwei Li, Xiaofen Su, Xinni Wang, Chunli Liu, Nuofu Zhang
Summary: The meta-analysis showed that non-benzodiazepine sedative hypnotics, especially eszopiclone, may increase CPAP adherence in OSA patients. Further investigation is needed to confirm the effects of zolpidem and zaleplon on CPAP adherence through larger scale, randomized, controlled trials.
Article
Psychiatry
Shoki Okuda, Zaina P. Qureshi, Yukiko Yanagida, Chie Ito, Yuji Homma, Shigeru Tokita
Summary: This study analyzed the prescribing patterns of hypnotics for treating insomnia in Japan using a claims database. The results showed that new users were mostly prescribed GABA(A)-receptor agonists, while long-term users preferred melatonin receptor agonists and orexin receptor antagonists. The findings suggest that more clinical evidence is needed to guide physicians in making optimal treatment decisions.
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)