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Suvorexant

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https://www.readbyqxmd.com/read/29112763/insight-into-reduction-of-wakefulness-by-suvorexant-in-patients-with-insomnia-analysis-of-wake-bouts
#1
Vladimir Svetnik, Ellen S Snyder, Peining Tao, Thomas E Scammell, Thomas Roth, Christopher Lines, W Joseph Herring
Objectives: To examine the duration and frequency of wake bouts underlying the wakefulness-after-sleep-onset (WASO) reduction with suvorexant. Methods: We analyzed polysomnogram recordings from clinical trials involving 1518 insomnia patients receiving suvorexant (40/30mg, 20/15mg) or placebo to determine: 1) the number of, and time spent in, long or short wake bouts, 2) the association between sleep quality and bout characteristics. We also compared wake and sleep bout characteristics of suvorexant in insomnia patients versus zolpidem in healthy subjects undergoing experimentally-induced transient insomnia...
November 3, 2017: Sleep
https://www.readbyqxmd.com/read/29066641/adverse-reaction-with-suvorexant-for-insomnia-acute-worsening-of-depression-with-emergence-of-suicidal-thoughts
#2
Jeremy Petrous, Kevin Furmaga
A 59-year-old woman on daily peritoneal dialysis for end-stage renal failure received care at an outpatient psychiatric clinic for her diagnoses that include major depressive disorder, generalised anxiety disorder and insomnia disorder. Although there was partial improvement in the patient's mood and anxiety symptoms with antidepressant treatment, insomnia remained a persistent complaint despite adequate trials of different sleep medications. The novel hypnotic, suvorexant (Belsomra, Merck & Co.) was then initiated at the recommended bedtime dose of 10 mg and was followed by a 15 mg dose the following night...
October 23, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28994603/suvorexant-scientifically-interesting-utility-uncertain
#3
Nicholas A Keks, Judy Hope, Simone Keogh
OBJECTIVE: Suvorexant, a new hypnotic, is indicated for the treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance, and is used long-term. This paper will briefly review suvorexant. RESULTS: Orexin is a hypothalamic peptide which promotes wakefulness. By blocking orexin receptors, suvorexant induces sleep. Peaking 2 h after ingestion, it has a half-life of 12 h and is hepatically metabolized mainly by CYP3A. Kinetics are not affected by age but concentrations are higher in females and obese patients...
October 1, 2017: Australasian Psychiatry: Bulletin of Royal Australian and New Zealand College of Psychiatrists
https://www.readbyqxmd.com/read/28992822/therapy-update-for-insomnia-in-the-elderly
#4
Sum Lam, Lucy O Macina
OBJECTIVE: To offer an update on insomnia in older adults and treatment options. DATA SOURCES: A search of PubMed using the terms "insomnia" and "older adults" was performed. Current guidelines, review articles, and drug database and manufacturer package inserts were utilized to provide relevant information. STUDY SELECTION: All English-language articles from 2012 to February 2017 and their bibliographies were reviewed for relevance. Current guidelines from the American College of Physicians, the American Academy of Sleep Medicine, and the American Geriatrics Society's Beers criteria were reviewed...
October 1, 2017: Consultant Pharmacist: the Journal of the American Society of Consultant Pharmacists
https://www.readbyqxmd.com/read/28798520/suvorexant
#5
REVIEW
(no author information available yet)
No abstract text is available yet for this article.
June 2017: Australian Prescriber
https://www.readbyqxmd.com/read/28767209/preventive-effects-of-suvorexant-on-delirium-a-randomized-placebo-controlled-trial
#6
Kotaro Hatta, Yasuhiro Kishi, Ken Wada, Takashi Takeuchi, Shigeo Ito, Akiko Kurata, Kazunori Murakami, Manabu Sugita, Chie Usui, Hiroyuki Nakamura
OBJECTIVE: No highly effective pharmacologic interventions to prevent delirium have been identified. We examined whether suvorexant, a potent and selective orexin receptor antagonist, is effective for the prevention of delirium. METHODS: We conducted a multicenter, rater-blinded, randomized, placebo-controlled clinical trial in intensive care units and regular acute wards between April 2015 and March 2016. Eligible patients were 65 to 89 years old, newly admitted due to emergency, and able to take medicine orally and had an expected stay or life expectancy of 48 hours or more...
August 1, 2017: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/28741623/effects-of-suvorexant-a-dual-orexin-hypocretin-receptor-antagonist-on-impulsive-behavior-associated-with-cocaine
#7
Taylor A Gentile, Steven J Simmons, Mia N Watson, Krista L Connelly, Eugen Brailoiu, Yanan Zhang, John W Muschamp
Hypothalamic hypocretin (orexin) peptides mediate arousal, attention, and reward processing. Fibers containing orexins project to brain structures that govern motivated behavior, including the ventral tegmental area (VTA). A number of psychiatric conditions, including attention deficit hyperactivity disorder (ADHD) and substance use disorders, are characterized by deficits in impulse control, however the relationship between orexin and impulsive behavior is incompletely characterized. The effects of systemic or centrally administered orexin receptor (OXR) antagonists on measures of impulsive-like behavior in rats were evaluated using the five-choice serial reaction time task (5-CSRTT) and delay discounting procedures...
July 25, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28725169/postoperative-delirium-after-pharyngolaryngectomy-with-esophagectomy-a-role-for-ramelteon-and-suvorexant
#8
Eisuke Booka, Yasuhiro Tsubosa, Teruaki Matsumoto, Mari Takeuchi, Takashi Kitani, Masato Nagaoka, Atsushi Imai, Tomoyuki Kamijo, Yoshiyuki Iida, Ayako Shimada, Katsushi Takebayashi, Masahiro Niihara, Keita Mori, Tetsuro Onitsuka, Hiroya Takeuchi, Yuko Kitagawa
BACKGROUND: Postoperative delirium is common after extensive surgery, and is known to be associated with sleeping medications. In this study, we aimed to investigate the relationships between sleeping medications and postoperative delirium after pharyngolaryngectomy with esophagectomy. METHODS: We performed a retrospective analysis of 65 patients who underwent pharyngolaryngectomy with esophagectomy at Shizuoka Cancer Center Hospital between January 2012 and March 2016...
2017: Esophagus: Official Journal of the Japan Esophageal Society
https://www.readbyqxmd.com/read/28671376/insomnia-pharmacologic-therapy
#9
REVIEW
Eric Matheson, Barry L Hainer
Insomnia accounts for more than 5.5 million visits to family physicians each year. Although behavioral interventions are the mainstay of treatment, pharmacologic therapy may be necessary for some patients. Understanding the risks and benefits of insomnia medications is critical. Controlled-release melatonin and doxepin are recommended as first-line agents in older adults; the so-called z-drugs (zolpidem, eszopiclone, and zaleplon) should be reserved for use if the first-line agents are ineffective. For the general population with difficulty falling asleep, controlled-release melatonin and the z-drugs can be considered...
July 1, 2017: American Family Physician
https://www.readbyqxmd.com/read/28663311/the-use-of-physiology-based-pharmacokinetic-and-pharmacodynamic-modeling-in-the-discovery-of-the-dual-orexin-receptor-antagonist-act-541468
#10
RANDOMIZED CONTROLLED TRIAL
Alexander Treiber, Ruben de Kanter, Catherine Roch, John Gatfield, Christoph Boss, Markus von Raumer, Benno Schindelholz, Clemens Muehlan, Joop van Gerven, Francois Jenck
The identification of new sleep drugs poses particular challenges in drug discovery owing to disease-specific requirements such as rapid onset of action, sleep maintenance throughout major parts of the night, and absence of residual next-day effects. Robust tools to estimate drug levels in human brain are therefore key for a successful discovery program. Animal models constitute an appropriate choice for drugs without species differences in receptor pharmacology or pharmacokinetics. Translation to man becomes more challenging when interspecies differences are prominent...
September 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28631980/orexin-research-patent-news-from-2016
#11
REVIEW
Christoph Boss, Catherine Roch
The orexin system consists of two G-protein-coupled receptors, orexin 1 and orexin 2 and two endogenous ligands, orexin A and orexin B . It is evolutionarily highly conserved. It is involved in the promotion of wakefulness as well as in anxiety and addictive disorders. In addition, its activation via the Ox1 receptor triggers apoptosis in several cancer cell lines. Dual orexin receptor antagonists are successfully used to treat primary insomnia. The major open questions are now related to the clinical validation of Ox1 selective antagonists...
October 2017: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/28584695/neuroendocrine-autonomic-and-metabolic-responses-to-an-orexin-antagonist-suvorexant-in-psychiatric-patients-with-insomnia
#12
Masaru Nakamura, Takahiko Nagamine
Aim: The aim of this study was to investigate the neuroendocrine, autonomic, and metabolic system responses to suvorexant in psychiatric subjects with insomnia. Design: This prospective study was conducted in Kusatsu Hospital in Hiroshima, Japan and included 40 psychiatric inpatients treated with suvorexant from December 2014 to April 2016. Methods: Questionnaire of Pittsburgh Sleep Quality Index (PSQI), Generalized Anxiety Disorder-7 (GAD-7), and Patient Health Questionnaire-9 (PHQ-9) scores were checked at baseline, Week 2, and Week 4, and fasting serum levels of prolactin, insulin, cortisol, noradrenaline, white blood cell count, and average pulse rate were measured at baseline and Week 4 and Week 8 after suvorexant initiation...
March 2017: Innovations in Clinical Neuroscience
https://www.readbyqxmd.com/read/28559480/in-vitro-and-in-silico-characterization-of-lemborexant-e2006-a-novel-dual-orexin-receptor-antagonist
#13
Carsten Theodor Beuckmann, Michiyuki Suzuki, Takashi Ueno, Kazuya Nagaoka, Tohru Arai, Hiroyuki Higashiyama
Orexin (hypocretin) neuropeptides have, among others, been implicated in arousal/sleep control, and antagonizing the orexin signaling pathway has been previously demonstrated to promote sleep in animals and humans. This mechanism opens up a new therapeutic approach to curb excessive wakefulness in insomnia disorder rather than to promote sleep-related signaling. Here we describe the preclinical pharmacological in vitro and in silico characterization of lemborexant ((1R,2S)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-2-(3-fluorophenyl)-N-(5-fluoropyridin-2-yl)cyclopropanecarboxamide)), a dual orexin receptor antagonist (DORA), as a novel experimental therapeutic agent for the symptomatic treatment of insomnia disorder and compare its properties to two other DORAs, almorexant and suvorexant...
August 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28520464/suvorexant-for-the-treatment-of-insomnia-in-adolescents
#14
Kentaro Kawabe, Fumie Horiuchi, Marina Ochi, Kayoko Nishimoto, Shu-Ichi Ueno, Yasunori Oka
OBJECTIVES: Suvorexant is the first dual orexin receptor antagonist for treating insomnia. This study aimed to evaluate the tolerability, efficacy, and safety of suvorexant on insomnia in adolescents. METHODS: Thirty patients (8 male and 22 female; mean standard deviation age: 15.7 ± 2.4 years; range: 10-20) with insomnia were administered suvorexant. Clinical background, persistence rate, the Clinical Global Impression (CGI), and the Athens Insomnia Scale (AIS) were compared between patients who continued and discontinued suvorexant treatment...
November 2017: Journal of Child and Adolescent Psychopharmacology
https://www.readbyqxmd.com/read/28447885/recovery-from-coma-post-cardiac-arrest-is-dependent-on-the-orexin-pathway
#15
Young-Jin Kang, Guilian Tian, Afsheen Bazrafkan, Maryam H Farahabadi, Matine Azadian, Hamidreza Abbasi, Brittany E Shamaoun, Oswald Steward, Yama Akbari
Cardiac arrest (CA) affects >550,000 people annually in the United States whereas 80-90% of survivors suffer from a comatose state. Arousal from coma is critical for recovery, but mechanisms of arousal are undefined. Orexin-A, a hypothalamic excitatory neuropeptide, has been linked to arousal deficits in various brain injuries. We investigated the orexinergic system's role in recovery from CA-related neurological impairments, including arousal deficits. Using an asphyxial CA and resuscitation model in rats, we examine neurological recovery post-resuscitation in conjunction with changes in orexin-A levels in cerebrospinal fluid (CSF) and orexin-expressing neurons...
October 1, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28427826/suvorexant-in-elderly-patients-with-insomnia-pooled-analyses-of-data-from-phase-iii-randomized-controlled-clinical-trials
#16
W Joseph Herring, Kathryn 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
OBJECTIVE: Suvorexant is an orexin receptor antagonist approved for treating insomnia at doses of 10-20 mg. Previously reported phase III results showed that suvorexant was effective and well-tolerated in a combined-age population (elderly and nonelderly adults). The present analysis evaluated the clinical profile of suvorexant specifically in the elderly. METHODS: Prespecified subgroup analyses of pooled 3-month data from two (efficacy) and three (safety) randomized, double-blind, placebo-controlled, parallel-group trials...
July 2017: American Journal of Geriatric Psychiatry
https://www.readbyqxmd.com/read/28419646/suvorexant-an-orexin-hypocretin-receptor-antagonist-attenuates-motivational-and-hedonic-properties-of-cocaine
#17
Taylor A Gentile, Steven J Simmons, David J Barker, Jessica K Shaw, Rodrigo A España, John W Muschamp
Orexins ('hypocretins') are peptides produced by neurons of the hypothalamus that project to structures implicated in reward and emotion processing. Converging evidence demonstrates functional roles of orexin signaling in arousal, sleep/wakefulness and motivated behaviors for natural and drug rewards. Suvorexant, a dual orexin receptor antagonist, recently received approval from the US Food and Drug Administration to treat insomnia. In Experiment 1, rats self-administered cocaine under a progressive-ratio schedule of reinforcement and the effects of suvorexant on motivation to self-administer cocaine were measured...
April 17, 2017: Addiction Biology
https://www.readbyqxmd.com/read/28376227/simple-and-highly-sensitive-uplc-esi-ms-ms-assay-for-rapid-determination-of-suvorexant-in-plasma
#18
Muzaffar Iqbal, Essam Ezzeldin, Nasr Y Khalil, Sara T A Al-Rashood, Khalid A Al-Rashood
Suvorexant is a dual orexin receptor antagonist, recently approved by USFDA for the treatment of insomnia. It is drug-of-abuse and listed in Schedule IV drug of the Controlled Substances Act. In this study, a simple and highly sensitive UPLC-MS/MS assay was developed and fully validated for the determination of suvorexant in rat plasma. Both suvorexant and internal standard (rivaroxaban; IS) were separated on Aquity BEHTM C18 column after the extraction form plasma using diethyl ether as extracting agent. An isocratic mobile phase, consisting of acetonitrile and 10 mM ammonium acetate in composition ratio of 85:15 was eluted at flow rate of 0...
March 1, 2017: Journal of Analytical Toxicology
https://www.readbyqxmd.com/read/28365447/suvorexant-for-the-treatment-of-primary-insomnia-a-systematic-review-and-meta-analysis
#19
REVIEW
Akira Kuriyama, Hiromitsu Tabata
Suvorexant is a dual orexin receptor agonist and is currently approved for the treatment of insomnia in the United States and Japan. We conducted a systematic review and meta-analysis to assess the efficacy and safety of suvorexant for the treatment of primary insomnia. We searched PubMed, EMBASE, and the Cochrane central register of controlled trials, contacted a relevant pharmaceutical company, and accessed websites of the U.S. Food and Drug Administration (FDA) and Pharmaceuticals and Medical Devices Agency (PMDA) for published and unpublished data...
October 2017: Sleep Medicine Reviews
https://www.readbyqxmd.com/read/28279667/preclinical-assessment-of-the-abuse-potential-of-the-orexin-receptor-antagonist-suvorexant
#20
Stephanie Born, David V Gauvin, Suman Mukherjee, Richard Briscoe
Suvorexant (Belsomra(®)) is a dual orexin receptor antagonist approved for the treatment of insomnia. Because of its pharmacology within the central nervous system, intended therapeutic indication, and first-in-class status, an assessment of suvorexant abuse liability potential was required prior to marketing approval. The nonclinical abuse liability potential studies for suvorexant included: 1) rat drug-dependence model to assess physical dependence following abrupt cessation; 2) rat drug-discrimination model to examine the potential similarity of the interoceptive or subjective effects of suvorexant to those elicited by zolpidem and morphine; 3) self-administration model to assess the relative reinforcing efficacy of suvorexant in rhesus monkeys conditioned to self-administer methohexital...
June 2017: Regulatory Toxicology and Pharmacology: RTP
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