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
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
Clinical Neurology
Michel A. Steiner, Michael Toeroek-Schafroth, Lisa Dacome, Michela Tessari
Summary: In order to assess abuse potential, the FDA requires new drugs that penetrate the brain to be compared to approved drugs that have similar mechanisms of action and are considered to have abuse liability. For the development of the dual orexin receptor antagonist daridorexant, the FDA recommended conducting a drug discrimination study in rats using the approved DORA suvorexant. Surprisingly, rats did not learn to distinguish suvorexant from placebo even at plasma levels up to three times the maximum approved human dose.
JOURNAL OF PSYCHOPHARMACOLOGY
(2023)
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.
Article
Chemistry, Organic
Hongshun Yuan, Lei Guo, Xianhua Pan
Summary: An efficient synthetic route for suvorexant without using chiral HPLC separation, resolution, enzyme catalysis or transition metal catalysis is reported, with a total yield up to 37%.
Article
Chemistry, Multidisciplinary
Mohammed H. Alqarni, Muzaffar Iqbal, Ahmed I. Foudah, Tariq M. Aljarba, Fatma Abdel Bar, Sultan Alshehri, Faiyaz Shakeel, Prawez Alam
Summary: Suvorexant is a new sedative/hypnotic medication, and this study proposed and validated a sensitive and rapid HPTLC bioanalytical method for determining its concentration in human urine samples.
Article
Clinical Neurology
Shadab A. Rahman, Margo D. Nathan, Aleta Wiley, Sybil Crawford, Aviva Y. Cohn, Jessica A. Harder, Leilah K. Grant, Athena Erickson, Akanksha Srivastava, Kathleen McCormick, Suzanne M. Bertisch, John W. Winkelman, Hadine Joffe
Summary: This study suggests that suvorexant is a well-tolerated and effective treatment option for VMS-associated insomnia disorder, reducing nighttime VMS symptoms. However, it did not significantly improve daytime VMS symptoms or other sleep-related outcomes.
Article
Pharmacology & Pharmacy
Ishani Landry, Nancy Hall, Jagadeesh Alur, Gleb Filippov, Larisa Reyderman, Beatrice Setnik, Jack Henningfield, Margaret Moline
Summary: In this study, the effects of therapeutic and supratherapeutic doses of lemborexant, zolpidem, and suvorexant on cognition and psychomotor performance were compared. The results showed that all active doses of the drugs increased reaction time and reduced divided attention capabilities, but lemborexant caused significantly less cognitive impairment than supratherapeutic doses of zolpidem in some measures.
JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY
(2022)
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
Behavioral Sciences
Francisco J. Flores-Ramirez, Jessica M. Illenberger, Glenn E. Pascasio, Alessandra Matzeu, Barbara J. Mason, Remi Martin-Fardon
Summary: Alcohol use disorder (AUD), a treatment-resistant medical condition, was studied using a dual orexin receptor antagonist, suvorexant, which was found to decrease alcohol intake and prevent stress-induced alcohol-seeking behavior in male rats with a history of alcohol dependence. Targeting the orexin system shows promise for the treatment of substance use disorders, including AUD.
FRONTIERS IN BEHAVIORAL NEUROSCIENCE
(2022)
Article
Neurosciences
Joseph A. Clerke, Mauro Congiu, Manuel Mameli
Summary: The epithalamic lateral habenula (LHb) plays a crucial role in mental illnesses and addiction, contributing to negative affective symptoms during withdrawal. Cellular and synaptic adaptations in the LHb are linked with addictive behaviors, highlighting the potential for targeting these adaptations as a strategy for treatment. Understanding the mechanisms in the LHb can lead to clinically-relevant approaches for specific aspects of drug addiction.
Review
Clinical Neurology
Yuki Shigetsura, Satoshi Imai, Hiroki Endo, Yumi Shimizu, Keita Ueda, Toshiya Murai, Kotaro Itohara, Shunsaku Nakagawa, Atsushi Yonezawa, Yasuaki Ikemi, Sachio Fukatsu, Noriaki Kitada, Tomohiro Terada, Takayuki Nakagawa, Kazuo Matsubara
Summary: This study investigated the effectiveness of switching from benzodiazepines to suvorexant or eszopiclone in managing benzodiazepine-unresponsive insomnia in patients with major depressive disorder. The results showed that both suvorexant and eszopiclone improved the severity of insomnia and were well tolerated. This suggests that these medications could be alternative options for treating insomnia in patients with major depressive disorder.
CLINICAL NEUROPHARMACOLOGY
(2022)
Article
Behavioral Sciences
Amy C. Beckenstrom, Preciosa M. Coloma, Gerard R. Dawson, Ailidh K. Finlayson, Asad Malik, Anke Post, Michel Alexander Steiner, Marc N. Potenza
Summary: Despite progress in understanding the pathological mechanisms underlying psychiatric disorders, translating from animal models into clinical use remains challenging. This article reviews outcome measures that may serve as markers of efficacy of orexin receptor modulators in humans as a potential treatment for psychiatric disorders. Challenges include the development, validation, and operationalization of these measures. Collaborative networks may help facilitate the validation of experimental medicine approaches in translational research and implementation in clinical practice.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2023)
Article
Pharmacology & Pharmacy
Ishani Landry, Nancy Hall, Jagadeesh Aluri, Gleb Filippov, Larisa Reyderman, Beatrice Setnik, Jack Henningfield, Margaret Moline
Summary: The study aimed to evaluate the abuse potential of Lemborexant, and the results showed that Lemborexant demonstrated similar abuse potential to other drugs and was well tolerated.
JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY
(2022)
Article
Oncology
Lars Guelen, Thierry O. Fischmann, Jerelyn Wong, Smita Mauze, Marco Guadagnoli, Nikolina Babala, Jozef Wagenaars, Veronica Juan, David Rosen, Winnie Prosise, Maurice Habraken, Imke Lodewijks, Danling Gu, Judith Stammen-Vogelzangs, Ying Yu, Jeanne Baker, David Lutje Hulsik, Lilian Driessen-Engels, Dan Malashock, Joost Kreijtz, Astrid Bertens, Evert de Vries, Astrid Bovens, Arne Bramer, Yiwei Zhang, Richard Wnek, Sean Troth, Elliot Chartash, Konstantin Dobrenkov, Svetlana Sadekova, Andrea van Elsas, Jason K. Cheung, Laurence Fayadat-Dilman, Jannie Borst, Amy M. Beebe, Hans Van Eenennaam
Summary: MK-5890, a novel CD27 agonistic antibody, has the potential to complement PD-1 checkpoint inhibition in cancer immunotherapy and is currently undergoing clinical evaluation.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Medicine, Legal
Fiona Sewell, Ian Ragan, Graham Horgan, David Andrew, Thomas Holmes, Irene Manou, Boris P. Mueller, Tim Rowan, Barbara G. Schmitt, Marco Corvaro
Summary: There are currently three test guidelines for acute oral toxicity studies, but the subjectivity of one guideline may be hindering its wider use. In order to address this, the NC3Rs and EPAA collaborated to analyze historical data and provide recommendations on the recognition of 'evident toxicity'.
REGULATORY TOXICOLOGY AND PHARMACOLOGY
(2024)
Article
Medicine, Legal
Michael DeVito, Bas Bokkers, Majorie B. M. van Duursen, Karin van Ede, Mark Feeley, Elsa Antunes Fernandes Gaspar, Laurie Haws, Sean Kennedy, Richard E. Peterson, Ron Hoogenboom, Keiko Nohara, Kim Petersen, Cynthia Rider, Martin Rose, Stephen Safe, Dieter Schrenk, Matthew W. Wheeler, Daniele S. Wikoff, Bin Zhao, Martin van den Berg
Summary: In October 2022, the World Health Organization reevaluated the toxic equivalency factors (TEFs) for chlorinated dioxin-like compounds in a panel convened in Lisbon. This effort utilized an updated database, Bayesian dose response modeling, and meta-analysis to derive Best-Estimate TEFs. Applying these new TEFs may result in lower total toxic equivalents for dioxin-like chemicals.
REGULATORY TOXICOLOGY AND PHARMACOLOGY
(2024)