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[PMID]:28273540
[Au] Autor:Fick J; Brodin T; Heynen M; Klaminder J; Jonsson M; Grabicova K; Randak T; Grabic R; Kodes V; Slobodnik J; Sweetman A; Earnshaw M; Barra Caracciolo A; Lettieri T; Loos R
[Ad] Endereço:Department of Chemistry, Umeå University, Sweden. Electronic address: jerker.fick@chem.umu.se.
[Ti] Título:Screening of benzodiazepines in thirty European rivers.
[So] Source:Chemosphere;176:324-332, 2017 Jun.
[Is] ISSN:1879-1298
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Pharmaceuticals as environmental contaminants have received a lot of interest over the past decade but, for several pharmaceuticals, relatively little is known about their occurrence in European surface waters. Benzodiazepines, a class of pharmaceuticals with anxiolytic properties, have received interest due to their behavioral modifying effect on exposed biota. In this study, our results show the presence of one or more benzodiazepine(s) in 86% of the analyzed surface water samples (n = 138) from 30 rivers, representing seven larger European catchments. Of the 13 benzodiazepines included in the study, we detected 9, which together showed median and mean concentrations (of the results above limit of quantification) of 5.4 and 9.6 ng L , respectively. Four benzodiazepines (oxazepam, temazepam, clobazam, and bromazepam) were the most commonly detected. In particular, oxazepam had the highest frequency of detection (85%) and a maximum concentration of 61 ng L . Temazepam and clobazam were found in 26% (maximum concentration of 39 ng L ) and 14% (maximum concentration of 11 ng L ) of the samples analyzed, respectively. Finally, bromazepam was found only in Germany and in 16 out of total 138 samples (12%), with a maximum concentration of 320 ng L . This study clearly shows that benzodiazepines are common micro-contaminants of the largest European river systems at ng L levels. Although these concentrations are more than a magnitude lower than those reported to have effective effects on exposed biota, environmental effects cannot be excluded considering the possibility of additive and sub-lethal effects.
[Mh] Termos MeSH primário: Benzodiazepinas/análise
Monitoramento Ambiental/métodos
Rios/química
Poluentes Químicos da Água/análise
[Mh] Termos MeSH secundário: Europa (Continente)
Oxazepam/análise
Temazepam/análise
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Water Pollutants, Chemical); 12794-10-4 (Benzodiazepines); 2MRO291B4U (clobazam); 6GOW6DWN2A (Oxazepam); CHB1QD2QSS (Temazepam)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170517
[Lr] Data última revisão:
170517
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170309
[St] Status:MEDLINE


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[PMID]:27534563
[Au] Autor:Wang X; Johansen SS; Zhang Y; Jia J; Rao Y; Jiang F; Linnet K
[Ad] Endereço:Section of Forensic Chemistry, Department of Forensic Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Frederik V's Vej 11, 2100, Copenhagen, Denmark. xinwangyao@163.com.
[Ti] Título:Deposition of diazepam and its metabolites in hair following a single dose of diazepam.
[So] Source:Int J Legal Med;131(1):131-141, 2017 Jan.
[Is] ISSN:1437-1596
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Only sporadic data are available on hair concentrations of diazepam and some of its metabolites (nordazepam, oxazepam, and temazepam) following a single controlled dose. The aim of this study was to investigate the deposition of diazepam and its metabolites in human hair after eight healthy volunteers (four women and four men, ages 24-26, East Asian) consumed 10 mg of diazepam. Hair was collected from all volunteers 1 month after exposure, and also 2 months post-exposure from men and 10 months post-exposure from women. Diazepam and the complete metabolite profile, including oxazepam glucuronide and temazepam glucuronide, were measured by ultra-high pressure liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) with limits of quantifications (LOQs) of 0.5-2.5 pg/mg for diazepam, nordazepam, oxazepam, and temazepam, and of 10 pg/mg for oxazepam glucuronide and temazepam glucuronide. There were no differences by gender in the amounts of diazepam or metabolites found. The concentration of the main metabolite nordazepam was consistently higher than that of diazepam at both 1 and 2 months after consumption. Oxazepam and temazepam traces were found in some volunteers' hair, but the glucuronides were not detected. Diazepam and nordazepam levels at 10 months post-exposure were extremely low (near the LOQ), indicating drug loss by personal hygiene and physical handling. To our knowledge, this is the first single-dose diazepam study using black hair and the first study to include measurements of oxazepam glucuronide and temazepam glucuronide in human hair.
[Mh] Termos MeSH primário: Diazepam/análise
Cabelo/química
Hipnóticos e Sedativos/análise
[Mh] Termos MeSH secundário: Adulto
Grupo com Ancestrais do Continente Asiático
Cromatografia Líquida
Diazepam/administração & dosagem
Feminino
Voluntários Saudáveis
Seres Humanos
Hipnóticos e Sedativos/administração & dosagem
Masculino
Nordazepam/análise
Oxazepam/análogos & derivados
Oxazepam/análise
Espectrometria de Massas em Tandem
Temazepam/análogos & derivados
Temazepam/análise
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Hypnotics and Sedatives); 26IK2C76NO (oxazepam glucuronide); 3703-53-5 (temazepam glucuronide); 67220MCM01 (Nordazepam); 6GOW6DWN2A (Oxazepam); CHB1QD2QSS (Temazepam); Q3JTX2Q7TU (Diazepam)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171017
[Lr] Data última revisão:
171017
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160819
[St] Status:MEDLINE
[do] DOI:10.1007/s00414-016-1429-x


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[PMID]:27434996
[Au] Autor:Mangel P; Matthews P; Levine B; Rosini J
[Ti] Título:Colonic Ischemia Leading to Colectomy in a Young Adult Prescribed Antipsychotic and Anxiolytic Medications.
[So] Source:Del Med J;88(5):146-7, 2016 May.
[Is] ISSN:0011-7781
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Ansiolíticos/efeitos adversos
Antipsicóticos/efeitos adversos
Colectomia
Megacolo/cirurgia
Isquemia Mesentérica/cirurgia
Temazepam/efeitos adversos
Cloridrato de Venlafaxina/efeitos adversos
[Mh] Termos MeSH secundário: Adulto
Seres Humanos
Masculino
Megacolo/induzido quimicamente
Isquemia Mesentérica/induzido quimicamente
Resultado do Tratamento
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Anxiety Agents); 0 (Antipsychotic Agents); 7D7RX5A8MO (Venlafaxine Hydrochloride); CHB1QD2QSS (Temazepam)
[Em] Mês de entrada:1608
[Cu] Atualização por classe:160720
[Lr] Data última revisão:
160720
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160721
[St] Status:MEDLINE


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[PMID]:26970544
[Au] Autor:Nakayama SM; Ikenaka Y; Hayami A; Mizukawa H; Darwish WS; Watanabe KP; Kawai YK; Ishizuka M
[Ad] Endereço:Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Kita-ku, Sapporo, Japan.
[Ti] Título:Characterization of equine cytochrome P450: role of CYP3A in the metabolism of diazepam.
[So] Source:J Vet Pharmacol Ther;39(5):478-87, 2016 Oct.
[Is] ISSN:1365-2885
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Research on drug metabolism and pharmacokinetics in large animal species including the horse is scarce because of the challenges in conducting in vivo studies. The metabolic reactions catalyzed by cytochrome P450s (CYPs) are central to drug pharmacokinetics. This study elucidated the characteristics of equine CYPs using diazepam (DZP) as a model compound as this drug is widely used as an anesthetic and sedative in horses, and is principally metabolized by CYPs. Diazepam metabolic activities were measured in vitro using horse and rat liver microsomes to clarify the species differences in enzyme kinetic parameters of each metabolite (temazepam [TMZ], nordiazepam [NDZ], p-hydroxydiazepam [p-OH-DZP], and oxazepam [OXZ]). In both species microsomes, TMZ was the major metabolite, but the formation rate of p-OH-DZP was significantly less in the horse. Inhibition assays with a CYP-specific inhibitors and antibody suggested that CYP3A was the main enzyme responsible for DZP metabolism in horse. Four recombinant equine CYP3A isoforms expressed in Cos-7 cells showed that CYP3A96, CYP3A94, and CYP3A89 were important for TMZ formation, whereas CYP3A97 exhibited more limited activity. Phylogenetic analysis suggested diversification of CYP3As in each mammalian order. Further study is needed to elucidate functional characteristics of each equine CYP3A isoform for effective use of diazepam in horses.
[Mh] Termos MeSH primário: Citocromo P-450 CYP3A/metabolismo
Diazepam/farmacocinética
Cavalos/metabolismo
Hipnóticos e Sedativos/farmacocinética
[Mh] Termos MeSH secundário: Animais
Células COS/enzimologia
Células COS/metabolismo
Cercopithecus aethiops
Citocromo P-450 CYP3A/genética
Diazepam/análogos & derivados
Masculino
Microssomos Hepáticos/enzimologia
Microssomos Hepáticos/metabolismo
Nordazepam/farmacocinética
Oxazepam/farmacocinética
Filogenia
Isoformas de Proteínas/metabolismo
Ratos
Ratos Sprague-Dawley
Especificidade da Espécie
Temazepam/farmacocinética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Hypnotics and Sedatives); 0 (Protein Isoforms); 17311-35-2 (4'-hydroxydiazepam); 67220MCM01 (Nordazepam); 6GOW6DWN2A (Oxazepam); CHB1QD2QSS (Temazepam); EC 1.14.14.1 (Cytochrome P-450 CYP3A); Q3JTX2Q7TU (Diazepam)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170623
[Lr] Data última revisão:
170623
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160313
[St] Status:MEDLINE
[do] DOI:10.1111/jvp.12303


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[PMID]:26779596
[Au] Autor:Plante DT; Goldstein MR; Cook JD; Smith R; Riedner BA; Rumble ME; Jelenchick L; Roth A; Tononi G; Benca RM; Peterson MJ
[Ad] Endereço:University of Wisconsin School of Medicine and Public Health, Department of Psychiatry, Madison, WI, USA. Electronic address: dplante@wisc.edu.
[Ti] Título:Effects of oral temazepam on slow waves during non-rapid eye movement sleep in healthy young adults: A high-density EEG investigation.
[So] Source:Int J Psychophysiol;101:25-32, 2016 Mar.
[Is] ISSN:1872-7697
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Slow waves are characteristic waveforms that occur during non-rapid eye movement (NREM) sleep that play an integral role in sleep quality and brain plasticity. Benzodiazepines are commonly used medications that alter slow waves, however, their effects may depend on the time of night and measure used to characterize slow waves. Prior investigations have utilized minimal scalp derivations to evaluate the effects of benzodiazepines on slow waves, and thus the topography of changes to slow waves induced by benzodiazepines has yet to be fully elucidated. This study used high-density electroencephalography (hdEEG) to evaluate the effects of oral temazepam on slow wave activity, incidence, and morphology during NREM sleep in 18 healthy adults relative to placebo. Temazepam was associated with significant decreases in slow wave activity and incidence, which were most prominent in the latter portions of the sleep period. However, temazepam was also associated with a decrease in the magnitude of high-amplitude slow waves and their slopes in the first NREM sleep episode, which was most prominent in frontal derivations. These findings suggest that benzodiazepines produce changes in slow waves throughout the night that vary depending on cortical topography and measures used to characterize slow waves. Further research that explores the relationships between benzodiazepine-induced changes to slow waves and the functional effects of these waveforms is indicated.
[Mh] Termos MeSH primário: Encéfalo/efeitos dos fármacos
Eletroencefalografia/efeitos dos fármacos
Hipnóticos e Sedativos/administração & dosagem
Sono/efeitos dos fármacos
Temazepam/administração & dosagem
[Mh] Termos MeSH secundário: Administração Oral
Adolescente
Adulto
Encéfalo/fisiologia
Feminino
Seres Humanos
Masculino
Sono/fisiologia
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Hypnotics and Sedatives); CHB1QD2QSS (Temazepam)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:170301
[Lr] Data última revisão:
170301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160119
[St] Status:MEDLINE


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[PMID]:25652266
[Au] Autor:Li J; Zhang J; Liu H; Wu L
[Ad] Endereço:Chinese Academy of Fishery Sciences, Quality and Standard Research Center, Beijing 100141, People's Republic of China.
[Ti] Título:A comparative study of primary secondary amino (PSA) and multi-walled carbon nanotubes (MWCNTs) as QuEChERS absorbents for the rapid determination of diazepam and its major metabolites in fish samples by high-performance liquid chromatography-electrospray ionisation-tandem mass spectrometry.
[So] Source:J Sci Food Agric;96(2):555-60, 2016 Jan 30.
[Is] ISSN:1097-0010
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: A simple and fast modified quick, easy, cheap, effective, rugged, and safe (QuEChERS) method is presented for the determination of diazepam and its three major metabolites, nordiazepam, temazepam and oxazepam (benzodiazepines) in fish samples by liquid chromatography-electrospray ionisation-tandem mass spectrometry. RESULTS: Muscle tissues were extracted with acetonitrile, and then cleaned with primary secondary amino (PSA) adsorbents. The cleanup effect of PSA was compared with that of multi-walled carbon nanotubes (MWCNTs) in term of extraction efficiency. The better results were obtained when PSA was used. The chromatography separation was achieved within 5.0 min on a C18 column. The limit of detection was 0.5 µg kg(-1) and the limit of quantification was 2.5 µg kg(-1). Average recoveries of diazepam and its main metabolites were in the range of 88.5-110.1%, with a relative standard deviation lower than 10.0%. CONCLUSION: The proposed method for fish samples gives good recoveries, linearity, precision and accuracy.
[Mh] Termos MeSH primário: Diazepam/análise
Peixes
Contaminação de Alimentos/análise
Nanotubos de Carbono/química
Alimentos Marinhos/análise
[Mh] Termos MeSH secundário: Adsorção
Animais
Cromatografia Líquida de Alta Pressão/métodos
Diazepam/metabolismo
Nordazepam/análise
Oxazepam/análise
Sensibilidade e Especificidade
Espectrometria de Massas por Ionização por Electrospray/métodos
Espectrometria de Massas em Tandem/métodos
Temazepam/análise
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Nanotubes, Carbon); 67220MCM01 (Nordazepam); 6GOW6DWN2A (Oxazepam); CHB1QD2QSS (Temazepam); Q3JTX2Q7TU (Diazepam)
[Em] Mês de entrada:1609
[Cu] Atualização por classe:151223
[Lr] Data última revisão:
151223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150206
[St] Status:MEDLINE
[do] DOI:10.1002/jsfa.7123


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[PMID]:26195197
[Au] Autor:Plante DT; Goldstein MR; Cook JD; Smith R; Riedner BA; Rumble ME; Jelenchick L; Roth A; Tononi G; Benca RM; Peterson MJ
[Ad] Endereço:University of Wisconsin-Madison, Department of Psychiatry, Madison, WI, United States. Electronic address: dplante@wisc.edu.
[Ti] Título:Effects of oral temazepam on sleep spindles during non-rapid eye movement sleep: A high-density EEG investigation.
[So] Source:Eur Neuropsychopharmacol;25(10):1600-10, 2015 Oct.
[Is] ISSN:1873-7862
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Benzodiazepines are commonly used medications that alter sleep spindles during non-rapid eye movement (NREM) sleep, however the topographic changes to these functionally significant waveforms have yet to be fully elucidated. This study utilized high-density electroencephalography (hdEEG) to investigate topographic changes in sleep spindles and spindle-range activity caused by temazepam during NREM sleep in 18 healthy adults. After an accommodation night, sleep for all participants was recorded on two separate nights after taking either placebo or oral temazepam 15 mg. Sleep was monitored using 256-channel hdEEG. Spectral analysis and spindle waveform detection of sleep EEG data were performed for each participant night. Global and topographic data were subsequently compared between temazepam and placebo conditions. Temazepam was associated with significant increases in spectral power from 10.33 to 13.83 Hz. Within this frequency band, temazepam broadly increased sleep spindle duration, and topographically increased spindle amplitude and density in frontal and central-posterior regions, respectively. Higher frequency sleep spindles demonstrated increased spindle amplitude and a paradoxical decrease in spindle density in frontal and centroparietal regions. Further analysis demonstrated temazepam both slowed the average frequency of spindle waveforms and increased the relative proportion of spindles at peak frequencies in frontal and centroparietal regions. These findings suggest that benzodiazepines have diverse effects on sleep spindles that vary by frequency and cortical topography. Further research that explores the relationships between topographic and frequency-dependent changes in pharmacologically-induced sleep spindles and the functional effects of these waveforms is indicated.
[Mh] Termos MeSH primário: Encéfalo/efeitos dos fármacos
Encéfalo/fisiologia
Hipnóticos e Sedativos/administração & dosagem
Fases do Sono/efeitos dos fármacos
Fases do Sono/fisiologia
Temazepam/administração & dosagem
[Mh] Termos MeSH secundário: Administração Oral
Adolescente
Adulto
Eletroencefalografia
Feminino
Seres Humanos
Masculino
Polissonografia
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Hypnotics and Sedatives); CHB1QD2QSS (Temazepam)
[Em] Mês de entrada:1607
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150722
[St] Status:MEDLINE


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[PMID]:26066943
[Au] Autor:Hansen RN; Boudreau DM; Ebel BE; Grossman DC; Sullivan SD
[Ad] Endereço:Ryan N. Hansen, Denise M. Boudreau, and Sean D. Sullivan are with the Pharmaceutical Outcomes Research and Policy Program, School of Pharmacy, University of Washington, Seattle. Denise M. Boudreau is also with and David C. Grossman is with the Group Health Research Institute, Seattle. Beth E. Ebel i
[Ti] Título:Sedative Hypnotic Medication Use and the Risk of Motor Vehicle Crash.
[So] Source:Am J Public Health;105(8):e64-9, 2015 Aug.
[Is] ISSN:1541-0048
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: We sought to estimate the association between sedative hypnotic use and motor vehicle crash risk. METHODS: We conducted a new user cohort study of 409 171 adults in an integrated health care system. Health plan data were linked to driver license and collision records. Participants were aged 21 years or older, licensed to drive in Washington State, had at least 1 year of continuous enrollment between 2003 and 2008, and were followed until death, disenrollment, or study end. We used proportional hazards regression to estimate the risk of crash associated with 3 sedatives. RESULTS: We found 5.8% of patients received new sedative prescriptions, with 11 197 person-years of exposure. New users of sedatives were associated with an increased risk of crash relative to nonuse: temazepam hazard ratio (HR) = 1.27 (95% confidence interval [CI] = 0.85, 1.91), trazodone HR = 1.91 (95% CI = 1.62, 2.25), and zolpidem HR = 2.20 (95% CI = 1.64, 2.95). These risk estimates are equivalent to blood alcohol concentration levels between 0.06% and 0.11%. CONCLUSIONS: New use of sedative hypnotics is associated with increased motor vehicle crash risk. Clinicians initiating sedative hypnotic treatment should consider length of treatment and counseling on driving risk.
[Mh] Termos MeSH primário: Acidentes de Trânsito/estatística & dados numéricos
Hipnóticos e Sedativos/efeitos adversos
[Mh] Termos MeSH secundário: Adulto
Feminino
Seres Humanos
Masculino
Meia-Idade
Medicamentos sob Prescrição/efeitos adversos
Modelos de Riscos Proporcionais
Piridinas/efeitos adversos
Fatores de Risco
Temazepam/efeitos adversos
Trazodona/efeitos adversos
Washington/epidemiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Hypnotics and Sedatives); 0 (Prescription Drugs); 0 (Pyridines); 7K383OQI23 (zolpidem); CHB1QD2QSS (Temazepam); YBK48BXK30 (Trazodone)
[Em] Mês de entrada:1604
[Cu] Atualização por classe:170801
[Lr] Data última revisão:
170801
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:150613
[St] Status:MEDLINE
[do] DOI:10.2105/AJPH.2015.302723


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[PMID]:25922426
[Au] Autor:Arbon EL; Knurowska M; Dijk DJ
[Ad] Endereço:Surrey Sleep Research Centre, University of Surrey, Guildford, UK.
[Ti] Título:Randomised clinical trial of the effects of prolonged-release melatonin, temazepam and zolpidem on slow-wave activity during sleep in healthy people.
[So] Source:J Psychopharmacol;29(7):764-76, 2015 Jul.
[Is] ISSN:1461-7285
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Current pharmacological treatments for insomnia include benzodiazepine and non-benzodiazepine hypnotics targeting γ-aminobutyric acid (GABA)A receptors, as well as agonists of the melatonin receptors MT1 and MT2. Melatonin, temazepam and zolpidem are thought to exert their effect through different mechanisms of action, but whether this leads to differential effects on electroencephalogram (EEG) power spectra during sleep in middle-aged people is currently not known. To establish whether the effects of prolonged-release melatonin (2 mg) on the nocturnal sleep EEG are different to those of temazepam (20 mg) and zolpidem (10 mg). Sixteen healthy men and women aged 55-64 years participated in a double-blind, placebo-controlled, four-way cross-over trial. Nocturnal sleep was assessed with polysomnography and spectral analysis of the EEG. The effects of single oral doses of prolonged-release melatonin, temazepam and zolpidem on EEG slow-wave activity (SWA, 0.75-4.5 Hz) and other frequencies during nocturnal non-rapid eye movement (NREM) sleep were compared. In an entire night analysis prolonged-release melatonin did not affect SWA, whereas temazepam and zolpidem significantly reduced SWA compared with placebo. Temazepam significantly reduced SWA compared with prolonged-release melatonin. Prolonged-release melatonin only reduced SWA during the first third of the night compared with placebo. These data show that the effects of prolonged-release melatonin on the nocturnal sleep EEG are minor and are different from those of temazepam and zolpidem; this is likely due to the different mechanisms of action of the medications.
[Mh] Termos MeSH primário: Melatonina/farmacologia
Piridinas/farmacologia
Sono/efeitos dos fármacos
Temazepam/farmacologia
[Mh] Termos MeSH secundário: Estudos Cross-Over
Preparações de Ação Retardada
Método Duplo-Cego
Eletroencefalografia
Feminino
Moduladores GABAérgicos/administração & dosagem
Moduladores GABAérgicos/farmacologia
Seres Humanos
Hipnóticos e Sedativos/administração & dosagem
Hipnóticos e Sedativos/farmacologia
Masculino
Melatonina/administração & dosagem
Meia-Idade
Polissonografia
Piridinas/administração & dosagem
Temazepam/administração & dosagem
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Delayed-Action Preparations); 0 (GABA Modulators); 0 (Hypnotics and Sedatives); 0 (Pyridines); 7K383OQI23 (zolpidem); CHB1QD2QSS (Temazepam); JL5DK93RCL (Melatonin)
[Em] Mês de entrada:1603
[Cu] Atualização por classe:150616
[Lr] Data última revisão:
150616
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150430
[St] Status:MEDLINE
[do] DOI:10.1177/0269881115581963


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[PMID]:25458535
[Au] Autor:Klein S; Bankstahl M; Gramer M; Hausknecht M; Löscher W
[Ad] Endereço:Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, Hannover, Germany; Center for Systems Neuroscience, Hannover, Germany.
[Ti] Título:Low doses of ethanol markedly potentiate the anti-seizure effect of diazepam in a mouse model of difficult-to-treat focal seizures.
[So] Source:Epilepsy Res;108(10):1719-27, 2014 Dec.
[Is] ISSN:1872-6844
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Ethanol is commonly used as a solvent in injectable formulations of poorly water-soluble drugs. The concentrations of ethanol in such formulations are generally considered reasonably safe. It is long known that ethanol can potentiate central effects of sedatives and tranquillizers, particularly the benzodiazepines, most likely as a result of a synergistic interaction at the GABAA receptor. However, whether this occurs at the low systemic doses of ethanol resulting from its use as solvent in parenteral formulations of benzodiazepines is not known. In the present study we evaluated whether a commercial ethanol-containing aqueous solution of diazepam exerts more potent anti-seizure effects than an aqueous solution of diazepam hydrochloride or an aqueous emulsion of this drug in the intrahippocampal kainate model of temporal lobe epilepsy in mice. Spontaneous epileptic seizures in this model are known to be resistant to major antiepileptic drugs. Administration of the ethanol-containing formulation of diazepam caused an almost complete suppression of seizures. This was not seen when the same dose (5 mg/kg) of diazepam was administered as aqueous solution or emulsion, although all three diazepam formulations resulted in similar drug and metabolite concentrations in plasma. Our data demonstrate that ethanol-containing solutions of diazepam are superior to block difficult-to-treat seizures to other formulations of diazepam. To our knowledge, this has not been demonstrated before and, if this finding can be translated to humans, may have important consequences for emergency treatment of acute seizures, series of seizures, and initial treatment of status epilepticus in patients.
[Mh] Termos MeSH primário: Anticonvulsivantes/administração & dosagem
Diazepam/administração & dosagem
Etanol
Convulsões/tratamento farmacológico
Solventes
[Mh] Termos MeSH secundário: Animais
Anticonvulsivantes/sangue
Anticonvulsivantes/química
Encéfalo/efeitos dos fármacos
Encéfalo/fisiopatologia
Diazepam/sangue
Diazepam/química
Modelos Animais de Doenças
Composição de Medicamentos
Sinergismo Farmacológico
Eletroencefalografia
Epilepsia do Lobo Temporal/tratamento farmacológico
Epilepsia do Lobo Temporal/fisiopatologia
Etanol/administração & dosagem
Etanol/sangue
Feminino
Ácido Caínico
Camundongos
Nordazepam/sangue
Oxazepam/sangue
Convulsões/fisiopatologia
Solventes/química
Solventes/farmacocinética
Temazepam/sangue
Água/química
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anticonvulsants); 0 (Solvents); 059QF0KO0R (Water); 3K9958V90M (Ethanol); 67220MCM01 (Nordazepam); 6GOW6DWN2A (Oxazepam); CHB1QD2QSS (Temazepam); Q3JTX2Q7TU (Diazepam); SIV03811UC (Kainic Acid)
[Em] Mês de entrada:1508
[Cu] Atualização por classe:141209
[Lr] Data última revisão:
141209
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:141203
[St] Status:MEDLINE



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