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Pesquisa : D03.383.679.600 [Categoria DeCS]
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PMID:29396378
Autor:Kori S; Parmar A; Goyal J; Sharma S
Endereço:Institute of Forensic Science & Criminology, Panjab University, Chandigarh 160 014, India.
Título:Cloud point extraction coupled with microwave-assisted back-extraction (CPE-MABE) for determination of Eszopiclone (Z-drug) using UV-Visible, HPLC and mass spectroscopic (MS) techniques: Spiked and in vivo analysis.
Fonte:J Chromatogr B Analyt Technol Biomed Life Sci; 1074-1075:129-138, 2018 Feb 01.
ISSN:1873-376X
País de publicação:Netherlands
Idioma:eng
Resumo:A procedure for the determination of Eszopiclone (ESZ) from complex matrices i.e. in vitro (spiked matrices), as well as in vivo (mice model) was developed using cloud point extraction coupled with microwave-assisted back-extraction (CPE-MABE). Analytical measurements have been carried using UV-Visible, HPLC and MS techniques. The proposed method has been validated according to ICH guidelines and legitimate reproducible and reliability of protocol is assessed through intraday and inter-day precision <3.61% and <4.70%, respectively. Limit of detection has been obtained as 0.083µg/mL and 0.472µg/mL respectively, for HPLC and UV-Visible techniques, corresponding to assessed linearity range. The coaservate phase in CPE was back extracted under microwaves exposure, with isooctane at pre-concentration factor ~50 when 5mL of sample solution was pre-concentrated to 0.1mL. Under optimized conditions i.e. Aqueous-Triton X-114 4% (w/v), pH4.0, NaCl 4% (w/v) and equilibrium temperature of 45°C for 20min, average extraction recovery has been obtained between 89.8 and 99.2% and 84.0-99.2% from UV-Visible and HPLC analysis, respectively. The method has been successfully applied to the pharmacokinetic estimation (post intraperitoneal administration) of ESZ in mice. MS analysis precisely depicted the presence of active N­desmethyl zopiclone in impales as well as in mice plasma.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:30IQX730WE (Polyethylene Glycols); 9036-19-5 (Nonidet P-40); UZX80K71OE (Eszopiclone)


  2 / 100 MEDLINE  
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PMID:28605546
Autor:Gerashchenko D; Pasumarthi RK; Kilduff TS
Endereço:Harvard Medical School/VA Medical Center, West Roxbury, MA.
Título:Plasticity-Related Gene Expression During Eszopiclone-Induced Sleep.
Fonte:Sleep; 40(7), 2017 Jul 01.
ISSN:1550-9109
País de publicação:United States
Idioma:eng
Resumo:Study Objectives: Experimental evidence suggests that restorative processes depend on synaptic plasticity changes in the brain during sleep. We used the expression of plasticity-related genes to assess synaptic plasticity changes during drug-induced sleep. Methods: We first characterized sleep induced by eszopiclone in mice during baseline conditions and during the recovery from sleep deprivation. We then compared the expression of 18 genes and two miRNAs critically involved in synaptic plasticity in these mice. Gene expression was assessed in the cerebral cortex and hippocampus by the TaqMan reverse transcription polymerase chain reaction and correlated with sleep parameters. Results: Eszopiclone reduced the latency to nonrapid eye movement (NREM) sleep and increased NREM sleep amounts. Eszopiclone had no effect on slow wave activity (SWA) during baseline conditions but reduced the SWA increase during recovery sleep (RS) after sleep deprivation. Gene expression analyses revealed three distinct patterns: (1) four genes had higher expression either in the cortex or hippocampus in the group of mice with increased amounts of wakefulness; (2) a large proportion of plasticity-related genes (7 out of 18 genes) had higher expression during RS in the cortex but not in the hippocampus; and (3) six genes and the two miRNAs showed no significant changes across conditions. Even at a relatively high dose (20 mg/kg), eszopiclone did not reduce the expression of plasticity-related genes during RS period in the cortex. Conclusions: These results indicate that gene expression associated with synaptic plasticity occurs in the cortex in the presence of a hypnotic medication.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Hypnotics and Sedatives); 0 (MicroRNAs); 0 (Sleep Aids, Pharmaceutical); UZX80K71OE (Eszopiclone)


  3 / 100 MEDLINE  
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PMID:28391425
Autor:Anand S; Tong H; Besag FMC; Chan EW; Cortese S; Wong ICK
Endereço:Department of Pharmacology and Pharmacy, Centre for Safe Medication Practice and Research, The University of Hong Kong, Pok Fu Lam, Hong Kong.
Título:Safety, Tolerability and Efficacy of Drugs for Treating Behavioural Insomnia in Children with Attention-Deficit/Hyperactivity Disorder: A Systematic Review with Methodological Quality Assessment.
Fonte:Paediatr Drugs; 19(3):235-250, 2017 Jun.
ISSN:1179-2019
País de publicação:Switzerland
Idioma:eng
Resumo:OBJECTIVE: A large proportion of paediatric patients with attention-deficit/hyperactivity disorder (ADHD) have associated sleep problems which not only affect the child's wellbeing but also impact family functioning. Management of sleep problems is consequently an important aspect of overall ADHD management in paediatric patients. Although some drugs are being used off-label for the management of paediatric insomnia, there is scant clinical evidence supporting their use. Our aim was to identify and assess the quality of published studies reporting the safety, tolerability and efficacy of drugs used for treating behavioural insomnia in children with ADHD. METHODS: After an initial screen to determine which drugs were most commonly used, we conducted a systematic review of English-language publications from searches of PubMed, EMBASE, PsycINFO and two trial register databases to February 2017, using keywords 'clonidine', 'melatonin', 'zolpidem', 'eszopiclone', 'L-theanine', 'guanfacine', 'ADHD', 'sleep disorder' and 'children'. For quality assessment of included studies, we used the CONSORT checklist for randomised control trials (RCTs) and the Downs and Black checklist for non-RCTs. RESULTS: Twelve studies were included. Two case series for clonidine, two RCTs and four observational studies for melatonin and one RCT each for zolpidem, eszopiclone, L-theanine and guanfacine. Of the 12 included studies, only one on eszopiclone scored excellent for quality. The quality of the rest of the studies varied from moderate to low. For clonidine, melatonin and L-theanine, improvements in sleep-onset latency and total sleep duration were reported; however, zolpidem, eszopiclone and guanfacine failed to show any improvement when compared with placebo. Clonidine, melatonin, L-theanine, eszopiclone and guanfacine were well tolerated with mild to moderate adverse events; zolpidem was associated with neuropsychiatric adverse effects. CONCLUSION: There is generally poor evidence for prescribing drugs for behavioural insomnia in children with ADHD. Further controlled studies are warranted.
Tipo de publicação: JOURNAL ARTICLE; REVIEW
Nome de substância:0 (Glutamates); 0 (Pyridines); 30OMY4G3MK (Guanfacine); 7K383OQI23 (zolpidem); 8021PR16QO (theanine); JL5DK93RCL (Melatonin); MN3L5RMN02 (Clonidine); UZX80K71OE (Eszopiclone)


  4 / 100 MEDLINE  
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Registro de Ensaios Clínicos
PMID:27634790
Autor:Edwards BA; Sands SA; Owens RL; Eckert DJ; Landry S; White DP; Malhotra A; Wellman A
Endereço:Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham & Women's Hospital & Harvard Medical School, Boston, MA.
Título:The Combination of Supplemental Oxygen and a Hypnotic Markedly Improves Obstructive Sleep Apnea in Patients with a Mild to Moderate Upper Airway Collapsibility.
Fonte:Sleep; 39(11):1973-1983, 2016 Nov 01.
ISSN:1550-9109
País de publicação:United States
Idioma:eng
Resumo:STUDY OBJECTIVES: Obstructive sleep apnea (OSA) results from the interaction of several physiological traits; specifically a compromised upper airway anatomy and muscle function, and two key non-anatomical deficits: elevated loop gain and a low arousal threshold. Although continuous positive airway pressure (CPAP) is an efficacious treatment, it is often poorly tolerated. An alternative approach could involve administering therapies targeting the non-anatomic causes. However, therapies (oxygen or hypnotics) targeting these traits in isolation typically improve, but rarely resolve OSA. Therefore, our aim was to determine how the combination of oxygen and eszopiclone alters the phenotypic traits and OSA severity and to assess the baseline phenotypic characteristics of responders/nonresponders to combination therapy. METHODS: In a single-blinded randomized crossover study, 20 OSA patients received combination therapy (3 mg eszopiclone and 40% oxygen) versus placebo/sham air, with 1 w between conditions. Under each condition, we assessed the effects on OSA severity (clinical polysomnography) and the phenotypic traits causing OSA using CPAP manipulations (research polysomnography). RESULTS: Combination therapy reduced the apnea-hypopnea index (51.9 ± 6.2 vs. 29.5 ± 5.3 events/h; P < 0.001), lowered both the ventilation associated with arousal (5.7 ± 0.3 vs. 5.2 ± 0.3 L/min; P = 0.05) and loop gain (3.3 ± 0.5 vs. 2.2 ± 0.3; P = 0.025). Responders to therapy (apnea-hypopnea index reduced by > 50% to below 15 events/h; n = 9/20) had less severe OSA (P = 0.001), a less collapsible upper airway (P = 0.01) and greater upper airway muscle effectiveness (P = 0.002). CONCLUSIONS: The combination of lowering loop gain and raising the arousal threshold is an effective therapy in patients whose anatomy is not severely compromised. Our work demonstrates that combining therapies that target multiple traits can resolve OSA in selected individuals. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT01633827.
Tipo de publicação: JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
Nome de substância:0 (Hypnotics and Sedatives); UZX80K71OE (Eszopiclone)


  5 / 100 MEDLINE  
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PMID:27486533
Autor:McGuire JM; Duquette M; Burghart SM; Ferri MJ
Endereço:Belmont University College of Pharmacy, Nashville, Tennessee.
Título:New-Onset Visual Hallucinations With Eszopiclone.
Fonte:Prim Care Companion CNS Disord; 18(2), 2016.
ISSN:2155-7780
País de publicação:United States
Idioma:eng
Tipo de publicação: CASE REPORTS; JOURNAL ARTICLE
Nome de substância:0 (Hypnotics and Sedatives); UZX80K71OE (Eszopiclone)


  6 / 100 MEDLINE  
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PMID:27206891
Autor:Ando T; Goto Y; Mano K
Endereço:Department of Neurology, Japanese Red Cross Nagoya Daiichi Hospital, 3-35 Michishita-cho Nakamura-ku, Nagoya, Aichi 453-8511, Japan. Electronic address: t.ando1229@gmail.com.
Título:Upper back restlessness: Two case reports.
Fonte:J Neurol Sci; 365:137-8, 2016 Jun 15.
ISSN:1878-5883
País de publicação:Netherlands
Idioma:eng
Tipo de publicação: CASE REPORTS; LETTER
Nome de substância:0 (Hypnotics and Sedatives); UZX80K71OE (Eszopiclone)


  7 / 100 MEDLINE  
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PMID:26943470
Autor:Tom SE; Wickwire EM; Park Y; Albrecht JS
Endereço:Pharmaceutical Health Services Research Department, University of Maryland School of Pharmacy, Baltimore, Maryland.
Título:Nonbenzodiazepine Sedative Hypnotics and Risk of Fall-Related Injury.
Fonte:Sleep; 39(5):1009-14, 2016 05 01.
ISSN:1550-9109
País de publicação:United States
Idioma:eng
Resumo:STUDY OBJECTIVES: The objective of this study was to test the hypothesis that use of zolpidem, eszopiclone, and zaleplon would be associated with increased risk of traumatic brain injury (TBI) and hip fracture. METHODS: We conducted a case-crossover study on a 5% random sample of Medicare beneficiaries age 65 y or older hospitalized with either TBI (n = 15,031) or hip fracture (n = 37,833) during 2007-2009. Use of zolpidem, eszopiclone, or zaleplon during the 30-day period prior to injury hospitalization was compared to use during four control periods at 3, 6, 9, and 12 mo prior to injury. The primary outcome was hospitalization for TBI or hip fracture. RESULTS: Zolpidem use during the month prior to injury was associated with increased risk of TBI (odds ratio [OR] 1.87; 95% confidence interval [CI] 1.56, 2.25); however, eszopiclone use during the same period was not associated with increased risk (OR 0.67; 95% CI 0.40, 1.13). Zolpidem use during the month prior to injury was associated with increased risk of hip fracture (OR 1.59; 95% CI 1.41, 1.79); however, eszopiclone use during the same period was not associated with increased risk (OR 1.12; 95% CI 0.83, 1.50). Analysis of zaleplon use in the month prior to injury was limited by low drug utilization but was not associated with increased risk of TBI (OR 0.85; 95% CI 0.21, 3.34) or hip fracture (OR 0.92; 95% CI 0.40, 2.13) in this study. CONCLUSIONS: For the treatment of insomnia in older adults, eszopiclone may present a safer alternative to zolpidem, in terms of fall-related injuries.
Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
Nome de substância:0 (Acetamides); 0 (Hypnotics and Sedatives); 0 (Pyridines); 0 (Pyrimidines); 7K383OQI23 (zolpidem); S62U433RMH (zaleplon); UZX80K71OE (Eszopiclone)


  8 / 100 MEDLINE  
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PMID:26943466
Autor:Tannenbaum PL; Tye SJ; Stevens J; Gotter AL; Fox SV; Savitz AT; Coleman PJ; Uslaner JM; Kuduk SD; Hargreaves R; Winrow CJ; Renger JJ
Endereço:Department of Pharmacology, Merck Research Laboratories, Merck & Co., Inc., West Point, PA.
Título:Inhibition of Orexin Signaling Promotes Sleep Yet Preserves Salient Arousability in Monkeys.
Fonte:Sleep; 39(3):603-12, 2016 Mar 01.
ISSN:1550-9109
País de publicação:United States
Idioma:eng
Resumo:STUDY OBJECTIVES: In addition to enhancing sleep onset and maintenance, a desirable insomnia therapeutic agent would preserve healthy sleep's ability to wake and respond to salient situations while maintaining sleep during irrelevant noise. Dual orexin receptor antagonists (DORAs) promote sleep by selectively inhibiting wake-promoting neuropeptide signaling, unlike global inhibition of central nervous system excitation by gamma-aminobutyric acid (GABA)-A receptor (GABAaR) modulators. We evaluated the effect of DORA versus GABAaR modulators on underlying sleep architecture, ability to waken to emotionally relevant stimuli versus neutral auditory cues, and performance on a sleepiness-sensitive cognitive task upon awakening. METHODS: DORA-22 and GABAaR modulators (eszopiclone, diazepam) were evaluated in adult male rhesus monkeys (n = 34) with continuous polysomnography recordings in crossover studies of sleep architecture, arousability to a classically conditioned salient versus neutral acoustical stimulus, and psychomotor vigilance task (PVT) performance if awakened. RESULTS: All compounds decreased wakefulness, but only DORA-22 sleep resembled unmedicated sleep in terms of underlying sleep architecture, preserved ability to awaken to salient-conditioned acoustic stimuli while maintaining sleep during neutral acoustic stimuli, and no congnitive impairment in PVT performance. Although GABAaR modulators induced lighter sleep, monkeys rarely woke to salient stimuli and PVT performance was impaired if monkeys were awakened. CONCLUSIONS: In nonhuman primates, DORAs' targeted mechanism for promoting sleep protects the ability to selectively arouse to salient stimuli and perform attentional tasks unimpaired, suggesting meaningful differentiation between a hypnotic agent that works through antagonizing orexin wake signaling versus the sedative hypnotic effects of the GABAaR modulator mechanism of action.
Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
Nome de substância:0 (DORA-22); 0 (GABA Agents); 0 (Hypnotics and Sedatives); 0 (Orexin Receptor Antagonists); 0 (Orexins); 0 (Piperidines); 0 (Triazoles); Q3JTX2Q7TU (Diazepam); UZX80K71OE (Eszopiclone)


  9 / 100 MEDLINE  
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Bittencourt, Lia Rita Azeredo
Tufik, Sérgio
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PMID:26872077
Autor:Pinto Jr LR; Bittencourt LR; Treptow EC; Braga LR; Tufik S
Endereço:Departamento de Psicobiologia, Universidade Federal de São Paulo (UNIFESP), São Paulo/, SP, Brazil.
Título:Eszopiclone versus zopiclone in the treatment of insomnia.
Fonte:Clinics (Sao Paulo); 71(1):5-9, 2016 Jan.
ISSN:1980-5322
País de publicação:Brazil
Idioma:eng
Resumo:OBJECTIVE: To determine the therapeutic effects of two selective GABA-A agonists, zopiclone and eszopiclone, in the treatment of insomnia. METHODS: This study comprised a phase III, single-center, randomized, double-blind, double-dummy, parallel-group, non-inferiority trial. Patients were randomized to receive zopiclone 7.5 mg or eszopiclone 3 mg, both orally, for four weeks. In total, 199 patients were evaluated during two visits and then followed for at least six weeks. The primary endpoint was the Insomnia Severity Index after four weeks of treatment. Secondary endpoints were obtained through polysomnography data, including total sleep time, sleep latency and sleep efficiency. The frequency of adverse events was also analyzed. ClinicalTrials.gov: NCT01100164. RESULTS: The primary efficacy analysis demonstrated the non-inferiority of eszopiclone over zopiclone. Analysis of objective parameters assessed by polysomnography showed that eszopiclone increased total sleep time and also improved sleep efficiency. The safety profile of both study treatments was similar and the most common events reported in both groups were dysgeusia, headache, dizziness, irritability and nausea. Adverse events were observed in 223 patients, 109 (85.2%) in the eszopiclone group and 114 (87.7%) in the zopiclone group. CONCLUSION: Based on the Insomnia Severity Index at the end of four weeks of treatment, eszopiclone demonstrated efficacy comparable to that of zopiclone in the treatment of insomnia, increasing total sleep time as well as sleep efficiency according to polysomnography.
Tipo de publicação: CLINICAL TRIAL, PHASE III; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL; RESEARCH SUPPORT, NON-U.S. GOV'T
Nome de substância:0 (Azabicyclo Compounds); 0 (Hypnotics and Sedatives); 0 (Piperazines); 03A5ORL08Q (zopiclone); UZX80K71OE (Eszopiclone)


  10 / 100 MEDLINE  
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PMID:26147892
Título:Drugs for Insomnia.
Fonte:Med Lett Drugs Ther; 57(1472):95-8, 2015 Jul 06.
ISSN:1523-2859
País de publicação:United States
Idioma:eng
Tipo de publicação: JOURNAL ARTICLE; REVIEW
Nome de substância:0 (Acetamides); 0 (Hypnotics and Sedatives); 0 (Plant Preparations); 0 (Pyridines); 0 (Pyrimidines); 7K383OQI23 (zolpidem); S62U433RMH (zaleplon); UZX80K71OE (Eszopiclone)



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