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Suvorexant

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https://www.readbyqxmd.com/read/28725169/postoperative-delirium-after-pharyngolaryngectomy-with-esophagectomy-a-role-for-ramelteon-and-suvorexant
#1
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
#2
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-pk-and-pd-modeling-in-the-discovery-of-the-dual-orexin-receptor-antagonist-act-541468
#3
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 due 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 in case inter-species differences are prominent...
June 29, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28631980/orexin-research-patent-news-from-2016
#4
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...
June 28, 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
#5
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
#6
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 (E2006: (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 for the symptomatic treatment of insomnia disorder, and compare its properties to two other DORAs, almorexant and suvorexant...
May 30, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28520464/suvorexant-for-the-treatment-of-insomnia-in-adolescents
#7
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...
May 18, 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
#8
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...
June 16, 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
#9
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
#10
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
#11
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
#12
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 28, 2016: Sleep Medicine Reviews
https://www.readbyqxmd.com/read/28279667/preclinical-assessment-of-the-abuse-potential-of-the-orexin-receptor-antagonist-suvorexant
#13
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...
March 6, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/28270270/a-review-of-suvorexant-doxepin-ramelteon-and-tasimelteon-for-the-treatment-of-insomnia-in-geriatric-patients
#14
REVIEW
Chelsey Edmonds, Michael Swanoski
Geriatric patients often experience insomnia because of physiological and neurological changes that occur during the aging process. Use of benzodiazepines, nonbenzodiazepine hypnotics, and diphenhydramine for the treatment of insomnia pose an increased risk of cognitive impairment, falls, and fractures in this patient population. Therapeutic alternatives approved by the Food and Drug Administration include suvorexant, doxepin, ramelteon, and tasimelteon, which have shown efficacy and safety in various studies...
March 1, 2017: Consultant Pharmacist: the Journal of the American Society of Consultant Pharmacists
https://www.readbyqxmd.com/read/28265715/clinical-profile-of-suvorexant-for-the-treatment-of-insomnia-over-3%C3%A2-months-in-women-and-men-subgroup-analysis-of-pooled-phase-3-data
#15
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
RATIONALE: Sex-related differences in the clinical profiles of some insomnia medications have been previously reported. OBJECTIVE: To evaluate the clinical profile of suvorexant, a novel orexin receptor antagonist approved for treating insomnia at doses up to 20 mg, by sex subgroups. METHODS: Efficacy analyses by sex were based on pooled data from two similar phase 3, randomized, double-blind, placebo-controlled, 3-month trials in elderly (≥65 years) and non-elderly (18-64 years) insomnia patients...
June 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28216404/discovery-of-novel-substituted-octahydropyrrolo-3-4-c-pyrroles-as-dual-orexin-receptor-antagonists-for-insomnia-treatment
#16
Songliang Wu, Yu Sun, Yi Hu, Hongmei Zhang, Lijuan Hou, Xing Liu, Yufeng Li, Haiying He, Zhi Luo, Yuan Chen, Yuhe Wang, Weihua Shi, Liang Shen, Changqing Cao, Wei Liang, Qing Xu, Qiang Lv, Jiong Lan, Jian Li, Shuhui Chen
A series of octahydropyrrolo[3,4-c]pyrroles were synthesized and evaluated by orexin 1 and 2 receptor (OX1 & 2 R) antagonists assays. Compound 14l with potent OXR antagonist activity and suitable pharmacokinetic behavior was chosen to be investigated in an EEG study, which demonstrated effects of sleep promotion comparable to Suvorexant. Furthermore, the di-fluro substituted analogs exhibited reduced hERG inhibition while maintaining moderate potency.
January 28, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28212694/suvorexant-induced-dream-enactment-behavior-in-parkinson-disease-a-case-report
#17
Hiromitsu Tabata, Akira Kuriyama, Fusae Yamao, Hiroshi Kitaguchi, Katsuro Shindo
Suvorexant is a new insomnia drug, and it is generally safe and well tolerated. Here, we report a rare but potentially important adverse effect of suvorexant in a patient with Parkinson disease.
May 15, 2017: Journal of Clinical Sleep Medicine: JCSM: Official Publication of the American Academy of Sleep Medicine
https://www.readbyqxmd.com/read/28075519/an-update-of-management-of-insomnia-in-patients-with-chronic-orofacial-pain
#18
REVIEW
Galit Almoznino, Yaron Haviv, Yair Sharav, Rafael Benoliel
In this review we discuss the management of chronic orofacial pain (COFP) patients with insomnia. Diagnostic work-up and follow-up routines of COFP patients should include assessment of sleep problems. Management is based on a multidisciplinary approach, addressing the factors that modulate the pain experience as well as insomnia and including both non-pharmacological and pharmacological modalities. Parallel to treatment, patients should receive therapy for co-morbid medical and psychiatric disorders, and possible substance abuse that may be that may trigger or worsen the COFP and/or their insomnia...
January 11, 2017: Oral Diseases
https://www.readbyqxmd.com/read/28035034/identification-of-suvorexant-in-urine-using-liquid-chromatography-quadrupole-time-of-flight-mass-spectrometry-lc-q-tof-ms
#19
Sydney Sullinger, Kelsie Bryand, Sarah Kerrigan
Suvorexant (Belsomra®) is a new hypnotic drug with a novel mechanism of action. In prescribed doses of 10 mg before bedtime, the drug produces rapid onset of sleep by inhibiting the orexin neurons of the arousal system, promoting decreased wakefulness. Suvorexant is a potent and highly selective dual orexin receptor antagonist. Sedative hypnotics are of forensic importance due to their widespread use, potential for additive effects with other central nervous system depressants, impairing effects and potential for misuse...
April 1, 2017: Journal of Analytical Toxicology
https://www.readbyqxmd.com/read/28012090/a-decade-of-orexin-hypocretin-and-addiction-where-are-we-now
#20
Morgan H James, Stephen V Mahler, David E Moorman, Gary Aston-Jones
One decade ago, our laboratory provided the first direct evidence linking orexin/hypocretin signaling with drug seeking by showing that activation of these neurons promotes conditioned morphine-seeking behavior. In the years since, contributions from many investigators have revealed roles for orexins in addiction for all drugs of abuse tested, but only under select circumstances. We recently proposed that orexins play a fundamentally unified role in coordinating "motivational activation" under numerous behavioral conditions, and here we unpack this hypothesis as it applies to drug addiction...
December 24, 2016: Current Topics in Behavioral Neurosciences
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