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https://www.readbyqxmd.com/read/27909991/the-role-of-orexins-hypocretins-in-alcohol-use-and-abuse
#1
Leigh C Walker, Andrew J Lawrence
Addiction is a chronic relapsing disorder characterized by compulsive drug seeking and drug taking despite negative consequences. Alcohol abuse and addiction have major social and economic consequences and cause significant morbidity and mortality worldwide. Currently available therapeutics are inadequate, outlining the need for alternative treatments. Detailed knowledge of the neurocircuitry and brain chemistry responsible for aberrant behavior patterns should enable the development of novel pharmacotherapies to treat addiction...
December 2, 2016: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/27909987/orexin-ox2-receptor-antagonists-as-sleep-aids
#2
Laura H Jacobson, Sui Chen, Sanjida Mir, Daniel Hoyer
The discovery of the orexin system represents the single major progress in the sleep field of the last three to four decades. The two orexin peptides and their two receptors play a major role in arousal and sleep/wake cycles. Defects in the orexin system lead to narcolepsy with cataplexy in humans and dogs and can be experimentally reproduced in rodents. At least six orexin receptor antagonists have reached Phase II or Phase III clinical trials in insomnia, five of which are dual orexin receptor antagonists (DORAs) that target both OX1 and OX2 receptors (OX2Rs)...
December 2, 2016: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/27860547/the-discovery-of-suvorexant-the-first-orexin-receptor-drug-for-insomnia
#3
Paul J Coleman, Anthony L Gotter, W Joseph Herring, Christopher J Winrow, John J Renger
Historically, pharmacological therapies have used mechanisms such as γ- aminobutyric acid A (GABAA) receptor potentiation to drive sleep through broad suppression of central nervous system activity. With the discovery of orexin signaling loss as the etiology underlying narcolepsy, a disorder associated with hypersomnolence, orexin antagonism emerged as an alternative approach to attenuate orexin-induced wakefulness more selectively. Dual orexin receptor antagonists (DORAs) block the activity of orexin 1 and 2 receptors to both reduce the threshold to transition into sleep and attenuate orexin-mediated arousal...
November 17, 2016: Annual Review of Pharmacology and Toxicology
https://www.readbyqxmd.com/read/27825624/quantification-of-suvorexant-in-urine-using-gas-chromatography-mass-spectrometry
#4
Mariah Carson, Sarah Kerrigan
Suvorexant (Belsomra(®)) is a novel sedative hypnotic drug that is prescribed to promote sleep in patients with insomnia. It is the first of a new class of drugs classified as dual orexin receptor antagonists (DORAs). Sedative hypnotics with central nervous system depressant effects feature prominently in forensic toxicology investigations. For this reason, a new analytical method was developed to identify suvorexant in urine using liquid-liquid extraction (LLE) and gas chromatography/mass spectrometry (GC/MS)...
November 2, 2016: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/27751669/review-of-safety-and-efficacy-of-sleep-medicines-in-older-adults
#5
REVIEW
Jennifer L Schroeck, James Ford, Erin L Conway, Kari E Kurtzhalts, Megan E Gee, Krista A Vollmer, Kari A Mergenhagen
PURPOSE: Insomnia is problematic for older adults. After behavioral modifications fail to show adequate response, pharmacologic options are used. The pharmacokinetics of agents used to treat insomnia may be altered. This review focuses on the safety and efficacy of medications used to treat insomnia. METHODS: A literature search of Medline, PubMed, and Embase was conducted (January 1966-June 2016). It included systematic reviews, randomized controlled trials, observational studies, and case series that had an emphasis on insomnia in an older population...
November 2016: Clinical Therapeutics
https://www.readbyqxmd.com/read/27631554/timed-inhibition-of-orexin-system-by-suvorexant-improved-sleep-and-glucose-metabolism-in-type-2-diabetic-db-db-mice
#6
Hiroshi Tsuneki, Kanta Kon, Hisakatsu Ito, Mitsuaki Yamazaki, Satoyuki Takahara, Naoki Toyooka, Yoko Ishii, Masakiyo Sasahara, Tsutomu Wada, Masashi Yanagisawa, Takeshi Sakurai, Toshiyasu Sasaoka
Sleep disturbances are associated with type 2 diabetes; therefore, the amelioration of sleep may improve metabolic disorders. To investigate this possibility, we here examined the effects of suvorexant, an antiinsomnia drug targeting the orexin system, on sleep and glucose metabolism in type 2 diabetic mice. Diabetic db/db mice had a longer wakefulness time during the resting period, as compared with nondiabetic db/m+ control mice. The single or 7-day administration of suvorexant at lights-on (ie, the beginning of the resting phase) increased nonrapid eye movement sleep time during the resting phase and, as a consequence, reduced awake time...
November 2016: Endocrinology
https://www.readbyqxmd.com/read/27554636/pharmacodynamic-effects-of-suvorexant-and-zolpidem-on-eeg-during-sleep-in-healthy-subjects
#7
Arie Struyk, Cynthia Gargano, Melissa Drexel, S Aubrey Stoch, Vladimir Svetnik, Junshui Ma, David Mayleben
The objective of this study was to evaluate sleep electrophysiology in healthy subjects after bedtime administration of therapeutic doses of two insomnia treatments - the orexin receptor antagonist suvorexant or the GABAergic agonist zolpidem. Eighteen healthy men received single bedtime doses of suvorexant 20mg, zolpidem 10mg, or placebo in a double-blinded, randomized, balanced 3-period crossover study. EEG power spectral densities during non-rapid eye movement (NREM) and rapid eye movement (REM) sleep were recorded in a polysomnography (PSG) laboratory using a 19-lead EEG recording array...
October 2016: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27471419/novel-class-of-medications-orexin-receptor-antagonists-in-the-treatment-of-insomnia-critical-appraisal-of-suvorexant
#8
REVIEW
Jessica L Norman, Sarah L Anderson
Insomnia, a highly prevalent disorder, can be detrimental to patients' overall health and worsen existing comorbidities. Patients may have acute episodes of insomnia related to a traumatic event, but more commonly insomnia occurs chronically. While proper sleep hygiene and behavioral therapy play important roles in the nonpharmacologic management of short-term and chronic insomnia, medications may also be required. Historically, insomnia has been treated with agents such as benzodiazepines, nonbenzodiazepine receptor agonists, and melatonin agonists...
2016: Nature and Science of Sleep
https://www.readbyqxmd.com/read/27430679/preclinical-and-clinical-results-of-dual-orexin-receptor-antagonist-suvorexant-belsomra-%C3%A2-a-novel-therapeutic-agent-for-insomnia
#9
Yoshitaka Tanaka, Ikuo Aoki, Takaaki Ishine, John J Renger, Christopher J Winrow, Satoru Hisada
No abstract text is available yet for this article.
July 2016: Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica
https://www.readbyqxmd.com/read/27424295/on-the-road-driving-performance-the-morning-after-bedtime-use-of-suvorexant-15-and-30%C3%A2-mg-in-healthy-elderly
#10
Annemiek Vermeeren, Eva Vets, Eric F P M Vuurman, Anita C M Van Oers, Stefan Jongen, Tine Laethem, Ingeborg Heirman, An Bautmans, John Palcza, Xiadong Li, Matthew D Troyer, Rebecca Wrishko, Jacqueline McCrea, Hong Sun
RATIONALE: Suvorexant is a first-in-class orexin receptor antagonist for treating insomnia. There is a general concern that hypnotics may impair next-morning driving ability. OBJECTIVE: The objective of this study was to evaluate next-morning driving performance in older adults after single and repeated doses of suvorexant. METHODS: Double-blind, randomized, placebo-controlled, 4-period crossover study in 24 healthy volunteers (10 females), aged 65-80 years...
September 2016: Psychopharmacology
https://www.readbyqxmd.com/read/27397664/suvorexant-in-patients-with-insomnia-pooled-analyses-of-three-month-data-from-phase-3-randomized-controlled-clinical-trials
#11
W Joseph Herring, Kathleen M Connor, Ellen Snyder, Duane B Snavely, Ying Zhang, Jill Hutzelmann, Deborah Matzura-Wolfe, Ruth M Benca, Andrew D Krystal, James K Walsh, Christopher Lines, Thomas Roth, David Michelson
STUDY OBJECTIVES: Suvorexant is an orexin receptor antagonist approved for treating insomnia at a maximum dose of 20 mg. Phase-3 trials evaluated two age-adjusted (non-elderly/elderly) dose-regimes of 40/30 mg and 20/15 mg with the primary focus on 40/30 mg. We report here results from pooled analyses of the 20/15 mg dose-regime, which was evaluated as a secondary objective in the trials. METHODS: Prespecified analysis of pooled data from two identical randomized, double-blind, placebo-controlled, parallel-group, 3-month trials in non-elderly (18-64 years) and elderly (≥ 65 years) patients with insomnia...
2016: Journal of Clinical Sleep Medicine: JCSM: Official Publication of the American Academy of Sleep Medicine
https://www.readbyqxmd.com/read/27390287/discovery-of-highly-potent-dual-orexin-receptor-antagonists-via-a-scaffold-hopping-approach
#12
Bibia Heidmann, John Gatfield, Catherine Roch, Alexander Treiber, Simone Tortoioli, Christine Brotschi, Jodi T Williams, Martin H Bolli, Stefan Abele, Thierry Sifferlen, François Jenck, Christoph Boss
Starting from suvorexant (trade name Belsomra), we successfully identified interesting templates leading to potent dual orexin receptor antagonists (DORAs) via a scaffold-hopping approach. Structure-activity relationship optimization allowed us not only to improve the antagonistic potency on both orexin 1 and orexin 2 receptors (Ox1 and Ox2, respectively), but also to increase metabolic stability in human liver microsomes (HLM), decrease time-dependent inhibition of cytochrome P450 (CYP) 3A4, and decrease P-glycoprotein (Pgp)-mediated efflux...
July 8, 2016: ChemMedChem
https://www.readbyqxmd.com/read/27340374/implications-of-recent-drug-approvals-for-older-adults
#13
Christine Eisenhower, Michael Koronkowski, Zachary Marcum
More than 100 medications were approved by the US Food and Drug Administration as new drugs or for new indications in 2014 and 2015. Several of the new drugs may benefit older adults, but adverse events and pharmacokinetic changes due to aging must be considered. This article will focus on three recently approved drugs that are marketed for chronic conditions that can affect older adults: suvorexant, for treatment of insomnia; edoxaban, for prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation and for treatment of venous thromboembolism; and droxidopa, for treatment of symptomatic neurogenic orthostatic hypotension...
January 2016: Annals of Long-term Care: the Official Journal of the American Medical Directors Association
https://www.readbyqxmd.com/read/27322687/mechanism-of-action-of-suvorexant
#14
Stephen M Stahl
Suovrexant is a novel hypnotic and is the only agent clinically available that works by blocking orexin-ergic mechanisms.
June 2016: CNS Spectrums
https://www.readbyqxmd.com/read/27304771/suvorexant-belsomra-for-insomnia
#15
Andrea R Gauld
No abstract text is available yet for this article.
June 15, 2016: American Family Physician
https://www.readbyqxmd.com/read/27253658/assessment-of-the-abuse-potential-of-the-orexin-receptor-antagonist-suvorexant-compared-with-zolpidem-in-a-randomized-crossover-study
#16
Kerri A Schoedel, Hong Sun, Edward M Sellers, Janice Faulknor, Naama Levy-Cooperman, Xiaodong Li, William P Kennedy, Jang-Ho Cha, Nicole M Lewis, Wen Liu, Phung Bondiskey, Jacqueline B McCrea, Deborah L Panebianco, Matthew D Troyer, John A Wagner
Suvorexant is a dual orexin receptor antagonist approved in the United States and Japan for the treatment of insomnia at a maximum dose of 20 mg. This randomized double-blind crossover study evaluated the abuse potential of suvorexant in 36 healthy recreational polydrug users with a history of sedative and psychedelic drug use. Single doses of suvorexant (40, 80, and 150 mg: 2-7.5 × maximum dose), zolpidem (15 and 30 mg: 1.5-3 × maximum dose), and placebo were administered, with a 10-day washout between treatments...
August 2016: Journal of Clinical Psychopharmacology
https://www.readbyqxmd.com/read/27198953/effects-of-suvorexant-on-sleep-architecture-and-power-spectral-profile-in-patients-with-insomnia-analysis-of-pooled-phase-3-data
#17
Ellen Snyder, Junshui Ma, Vladimir Svetnik, Kathryn M Connor, Christopher Lines, David Michelson, W Joseph Herring
BACKGROUND: The orexin receptor antagonist, suvorexant, is approved for treating insomnia at a maximum dose of 20 mg. We evaluated its effects on sleep architecture. METHODS: The analyses included pooled polysomnography data from two similar randomized, double-blind, placebo-controlled, 3-month trials evaluating two age-adjusted (non-elderly/elderly) dose regimes of 20/15 mg and 40/30 mg in 1482 patients with insomnia. Polysomnography was recorded at baseline and on three nights during the treatment: Night-1, Month-1, and Month-3...
March 2016: Sleep Medicine
https://www.readbyqxmd.com/read/27191770/induced-next-day-somnolence-in-an-elderly-patient-taking-suvorexant-concomitantly-with-diltiazem
#18
Atsuko Shihyakugari, Satoko Hori, Akiko Miki, Yasufumi Sawada
OBJECTIVE: To present the first case of induced next-day somnolence in a patient taking suvorexant concomitantly with diltiazem. CASE SUMMARY: The patient was an 88-year-old female who had suffered from insomnia and anorexia, for which a psychiatric clinic had prescribed 1.5 mg/day aripiprazole and 15 mg/day suvorexant (both once daily at bedtime), which cured her insomnia. Subsequently, a different hospital prescribed diltiazem hydrochloride (100 mg, sustained-release, daily after breakfast) for treatment of hypertension...
August 2016: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27136278/pharmacologic-treatment-of-insomnia-disorder-an-evidence-report-for-a-clinical-practice-guideline-by-the-american-college-of-physicians
#19
Timothy J Wilt, Roderick MacDonald, Michelle Brasure, Carin M Olson, Maureen Carlyle, Erika Fuchs, Imran S Khawaja, Susan Diem, Erin Koffel, Jeannine Ouellette, Mary Butler, Robert L Kane
BACKGROUND: Pharmacologic interventions are often prescribed for insomnia disorder. PURPOSE: To assess the benefits, harms, and comparative effectiveness of pharmacologic treatments for adults with insomnia disorder. DATA SOURCES: Several electronic databases (2004-September 2015), reference lists, and U.S. Food and Drug Administration (FDA) documents. STUDY SELECTION: 35 randomized, controlled trials of at least 4 weeks' duration that evaluated pharmacotherapies available in the United States and that reported global or sleep outcomes; 11 long-term observational studies that reported harm information; FDA review data for nonbenzodiazepine hypnotics and orexin receptor antagonists; and product labels for all agents...
July 19, 2016: Annals of Internal Medicine
https://www.readbyqxmd.com/read/26955275/suvorexant-a-promising-novel-treatment-for-insomnia
#20
REVIEW
Joyce K Lee-Iannotti, James M Parish
Suvorexant a novel, orexin receptor antagonist was recently approved by the US Food and Drug Administration for the treatment of sleep onset and sleep maintenance insomnia in August 2014. Multiple animal and human studies support the efficacy, safety, and tolerability of suvorexant for patients of various profiles. Current recommendations advocate for a starting dose of 10 mg and a maximum dose of 20 mg, with cautious use in women, obese patients, and patients taking other CYP3A4 inhibitors. More head-to-head studies comparing suvorexant to other sedative-hypnotic therapies are needed to further delineate which patients will benefit the most from this medication over others...
2016: Neuropsychiatric Disease and Treatment
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