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[PMID]:29308828
[Au] Autor:Lewis SR; Schofield-Robinson OJ; Alderson P; Smith AF
[Ad] Endereço:Patient Safety Research Department, Royal Lancaster Infirmary, Pointer Court 1, Ashton Road, Lancaster, UK, LA1 4RP.
[Ti] Título:Propofol for the promotion of sleep in adults in the intensive care unit.
[So] Source:Cochrane Database Syst Rev;1:CD012454, 2018 Jan 08.
[Is] ISSN:1469-493X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: People in the intensive care unit (ICU) experience sleep deprivation caused by environmental disruption, such as high noise levels and 24-hour lighting, as well as increased patient care activities and invasive monitoring as part of their care. Sleep deprivation affects physical and psychological health, and people perceive the quality of their sleep to be poor whilst in the ICU. Propofol is an anaesthetic agent which can be used in the ICU to maintain patient sedation and some studies suggest it may be a suitable agent to replicate normal sleep. OBJECTIVES: To assess whether the quantity and quality of sleep may be improved by administration of propofol to adults in the ICU and to assess whether propofol given for sleep promotion improves both physical and psychological patient outcomes. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 10), MEDLINE (1946 to October 2017), Embase (1974 to October 2017), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1937 to October 2017) and PsycINFO (1806 to October 2017). We searched clinical trials registers for ongoing studies, and conducted backward and forward citation searching of relevant articles. SELECTION CRITERIA: We included randomized and quasi-randomized controlled trials with adults, over the age of 16 years, admitted to the ICU with any diagnoses, given propofol versus a comparator to promote overnight sleep. We included participants who were and were not mechanically ventilated. We included studies that compared the use of propofol, given at an appropriate clinical dose with the intention of promoting night-time sleep, against: no agent; propofol at a different rate or dose; or another agent, administered specifically to promote sleep. We included only studies in which propofol was given during 'normal' sleeping hours (i.e. between 10 pm and 7 am) to promote a sleep-like state with a diurnal rhythm. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, extracted data, assessed risk of bias and synthesized findings. MAIN RESULTS: We included four studies with 149 randomized participants. We identified two studies awaiting classification for which we were unable to assess eligibility and one ongoing study.Participants differed in severity of illness as assessed by APACHE II scores in three studies and further differences existed between comparisons and methods. One study compared propofol versus no agent, one study compared different doses of propofol and two studies compared propofol versus a benzodiazepine (flunitrazepam, one study; midazolam, one study). All studies reported randomization and allocation concealment inadequately. We judged all studies to have high risk of performance bias from personnel who were unblinded. We noted that some study authors had blinded study outcome assessors and participants for relevant outcomes.It was not appropriate to combine data owing to high levels of methodological heterogeneity.One study comparing propofol with no agent (13 participants) measured quantity and quality of sleep using polysomnography; study authors reported no evidence of a difference in duration of sleep or sleep efficiency, and reported disruption to usual REM (rapid eye movement sleep) with propofol.One study comparing different doses of propofol (30 participants) measured quantity and quality of sleep by personnel using the Ramsay Sedation Scale; study authors reported that more participants who were given a higher dose of propofol had a successful diurnal rhythm, and achieved a greater sedation rhythmicity.Two studies comparing propofol with a different agent (106 participants) measured quantity and quality of sleep using the Pittsburgh Sleep Diary and the Hospital Anxiety and Depression Scale; one study reported fewer awakenings of reduced duration with propofol, and similar total sleep time between groups, and one study reported no evidence of a difference in sleep quality. One study comparing propofol with another agent (66 participants) measured quantity and quality of sleep with the Bispectral Index and reported longer time in deep sleep, with fewer arousals. One study comparing propofol with another agent (40 participants) reported higher levels of anxiety and depression in both groups, and no evidence of a difference when participants were given propofol.No studies reported adverse events.We used the GRADE approach to downgrade the certainty of the evidence for each outcome to very low. We identified sparse data with few participants, and methodological differences in study designs and comparative agents introduced inconsistency, and we noted that measurement tools were imprecise or not valid for purpose. AUTHORS' CONCLUSIONS: We found insufficient evidence to determine whether administration of propofol would improve the quality and quantity of sleep in adults in the ICU. We noted differences in study designs, methodology, comparative agents and illness severity amongst study participants. We did not pool data and we used the GRADE approach to downgrade the certainty of our evidence to very low.
[Mh] Termos MeSH primário: Dissonias/tratamento farmacológico
Hipnóticos e Sedativos/uso terapêutico
Unidades de Terapia Intensiva
Propofol/uso terapêutico
Sono/efeitos dos fármacos
[Mh] Termos MeSH secundário: Adulto
Flunitrazepam/uso terapêutico
Seres Humanos
Midazolam/uso terapêutico
Ensaios Clínicos Controlados Aleatórios como Assunto
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Hypnotics and Sedatives); 620X0222FQ (Flunitrazepam); R60L0SM5BC (Midazolam); YI7VU623SF (Propofol)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180109
[St] Status:MEDLINE
[do] DOI:10.1002/14651858.CD012454.pub2


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[PMID]:27957675
[Au] Autor:Talarek S; Listos J; Orzelska-Gorka J; Jakobczuk M; Kotlinska J; Biala G
[Ad] Endereço:Chair and Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Chodzki 4A, 20-093, Lublin, Poland. sylwia.talarek@umlub.pl.
[Ti] Título:The Importance of L-Arginine:NO:cGMP Pathway in Tolerance to Flunitrazepam in Mice.
[So] Source:Neurotox Res;31(2):309-316, 2017 Feb.
[Is] ISSN:1476-3524
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The goal of the study was to investigate the effects of drugs modifying L-arginine:NO:cGMP pathway on the development of tolerance to flunitrazepam (FNZ)-induced motor impairment in mice. FNZ-induced motor incoordination was assessed on the 1st and 8th days of experiment, using the rotarod and chimney tests. It was found that (a) both a non-selective nitric oxide synthase (NOS) inhibitor: N -nitro-L-arginine methyl ester (L-NAME) and an unselective neuronal NOS inhibitor: 7-nitroindazole (7-NI) inhibited the development of tolerance to the motor-impairing effects of FNZ in the rotarod and the chimney tests and (b) both a NO precursor: L-arginine and a selective inhibitor of phosphodiesterase 5 (PDE5): sildenafil did not affect the development of tolerance to FNZ-induced motor impairment in mice. Those findings provided behavioural evidence that NO could contribute an important role in the development of tolerance to FNZ in mice.
[Mh] Termos MeSH primário: Arginina/farmacologia
Tolerância a Medicamentos/fisiologia
Flunitrazepam/farmacologia
Óxido Nítrico/fisiologia
Transdução de Sinais/fisiologia
[Mh] Termos MeSH secundário: Animais
GMP Cíclico/fisiologia
Interações Medicamentosas
Indazóis/farmacologia
Masculino
Camundongos
Destreza Motora/efeitos dos fármacos
NG-Nitroarginina Metil Éster/farmacologia
Transdução de Sinais/efeitos dos fármacos
Citrato de Sildenafila/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Indazoles); 31C4KY9ESH (Nitric Oxide); 620X0222FQ (Flunitrazepam); 94ZLA3W45F (Arginine); BW9B0ZE037 (Sildenafil Citrate); H2D2X058MU (Cyclic GMP); UX0N37CMVH (7-nitroindazole); V55S2QJN2X (NG-Nitroarginine Methyl Ester)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171010
[Lr] Data última revisão:
171010
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161214
[St] Status:MEDLINE
[do] DOI:10.1007/s12640-016-9688-3


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[PMID]:26990972
[Au] Autor:Ali EM; Edwards HG
[Ad] Endereço:Department of Forensic Medicine and Clinical Toxicology, Sohag Faculty of Medicine, Sohag, Egypt.
[Ti] Título:The detection of flunitrazepam in beverages using portable Raman spectroscopy.
[So] Source:Drug Test Anal;9(2):256-259, 2017 Feb.
[Is] ISSN:1942-7611
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Portable Raman spectroscopy has been used for the detection of the date-rape drug flunitrazepam in spiked beverages that may be involved in cases of drug-facilitated sexual assault. Solutions of flunitrazepam with different concentrations were prepared in water and for each beverage type. Although some bands attributable to the beverage matrix are present, they did not interfere with the identification of the drug. Definitive evidence for contamination of the spiked drink concerned can be acquired within 10 s. The data can be acquired in situ and sample extraction and/or preparation steps are unnecessary. The ability of portable Raman spectrometers to interrogate spiked alcoholic beverages with flunitrazepam has been demonstrated. Copyright © 2016 John Wiley & Sons, Ltd.
[Mh] Termos MeSH primário: Bebidas Alcoólicas/análise
Ansiolíticos/análise
Flunitrazepam/análise
Análise Espectral Raman/métodos
[Mh] Termos MeSH secundário: Seres Humanos
Limite de Detecção
Estupro
Detecção do Abuso de Substâncias/métodos
[Pt] Tipo de publicação:EVALUATION STUDIES; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Anxiety Agents); 620X0222FQ (Flunitrazepam)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170630
[Lr] Data última revisão:
170630
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160319
[St] Status:MEDLINE
[do] DOI:10.1002/dta.1969


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[PMID]:27871507
[Au] Autor:Hertle DN; Beynon C; Neumann JO; Santos E; Sánchez-Porras R; Unterberg AW; Sakowitz OW
[Ad] Endereço:Department of Neurosurgery, University of Heidelberg, 69120 Heidelberg, Germany. Electronic address: daniel.hertle@med.uni-heidelberg.de.
[Ti] Título:Use of GABAergic sedatives after subarachnoid hemorrhage is associated with worse outcome-preliminary findings.
[So] Source:J Clin Anesth;35:118-122, 2016 Dec.
[Is] ISSN:1873-4529
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:STUDY OBJECTIVE: Recent experimental evidence identified GABAergic sedation as a possible cause for deprived neuroregeneration and poor outcome after acute brain injury. Patients with aneurysmal subarachnoid hemorrhage are often sedated, and GABAergic sedation, such as midazolam and propofol, is commonly used. DESIGN: Retrospective cohort study based on a prospectively established database. SETTING: Single-center neurointensive care unit. PATIENTS: Twenty-nine patients after subarachnoid hemorrhage. INTERVENTION: Noninterventional study. MEASUREMENTS: The relationship between mean GABAergic sedative dose during the acute phase and outcome after 6 months according to the Glasgow Outcome Scale, and initial Glasgow Coma Scale was investigated. MAIN RESULTS: Use of GABAergic sedatives was negatively correlated with Glasgow Outcome Scale (r =0.267; P=.008). Administration of sedatives was independent of the initial Glasgow Coma Scale. GABAergic sedatives flunitrazepam, midazolam, and propofol were used differently during the first 10 days after ictus. CONCLUSION: Administration of GABAergic sedation was associated with an unfavorable outcome after 6 months. To avoid bias (mainly through the indication to use sedation), additional experimental and comparative clinical investigation of, for example, non-GABAergic sedation, and clinical protocols of no sedation is necessary.
[Mh] Termos MeSH primário: Encéfalo/fisiologia
Moduladores GABAérgicos/efeitos adversos
Hipnóticos e Sedativos/efeitos adversos
Regeneração/efeitos dos fármacos
Hemorragia Subaracnóidea/tratamento farmacológico
[Mh] Termos MeSH secundário: Adulto
Idoso
Sedação Consciente/métodos
Feminino
Flunitrazepam/administração & dosagem
Flunitrazepam/efeitos adversos
Flunitrazepam/uso terapêutico
Moduladores GABAérgicos/administração & dosagem
Moduladores GABAérgicos/uso terapêutico
Escala de Coma de Glasgow
Seres Humanos
Hipnóticos e Sedativos/administração & dosagem
Hipnóticos e Sedativos/uso terapêutico
Masculino
Midazolam/administração & dosagem
Midazolam/efeitos adversos
Midazolam/uso terapêutico
Meia-Idade
Propofol/administração & dosagem
Propofol/efeitos adversos
Propofol/uso terapêutico
Estudos Retrospectivos
Hemorragia Subaracnóidea/complicações
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (GABA Modulators); 0 (Hypnotics and Sedatives); 620X0222FQ (Flunitrazepam); R60L0SM5BC (Midazolam); YI7VU623SF (Propofol)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161123
[St] Status:MEDLINE


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[PMID]:27127911
[Au] Autor:Orzelska-Gorka J; Talarek S; Listos J; Kedzierska E; Fidecka S
[Ad] Endereço:Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Lublin, Poland. Electronic address: jolanta.orzelska@umlub.pl.
[Ti] Título:l-NAME differential effects on diazepam and flunitrazepam responses of rats in the object recognition test.
[So] Source:Pharmacol Rep;68(4):728-32, 2016 Aug.
[Is] ISSN:1734-1140
[Cp] País de publicação:Poland
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The present study was undertaken to better understand possible interaction(s) between a non-selective nitric oxide inhibitor: N(G)-nitro-l-arginine methyl ester (l-NAME) and benzodiazepines (BZs) in recognition memory. METHODS: The study was carried out on adult male albino Wistar rats. A novel object recognition (NOR) task was used to evaluate memory process. RESULTS: Combined administration of l-NAME (50mg/kg, ip) with a threshold dose of DZ (0.25mg/kg) induced amnesic effects in rats, participating in the NOR test. On the other hand, following a combined administration of l-NAME (100mg/kg, ip) with flunitrazepam (FNZ; 0.1mg/kg), it was found out that l-NAME inhibited the amnesic effects of FNZ on rats in the NOR test. CONCLUSIONS: The obtained results suggest that suppressed NO synthesis may lead to a facilitation of DZ-induced memory impairment but surprisingly may prevent amnesic effect after FNZ in rats, submitted to NOR task.
[Mh] Termos MeSH primário: Diazepam/farmacologia
Flunitrazepam/farmacologia
NG-Nitroarginina Metil Éster/farmacologia
Recognição (Psicologia)/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Relação Dose-Resposta a Droga
Interações Medicamentosas
Masculino
Ratos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
620X0222FQ (Flunitrazepam); Q3JTX2Q7TU (Diazepam); V55S2QJN2X (NG-Nitroarginine Methyl Ester)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170619
[Lr] Data última revisão:
170619
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160430
[St] Status:MEDLINE


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[PMID]:27051273
[Au] Autor:Svob Strac D; Vlainic J; Samardzic J; Erhardt J; Krsnik Z
[Ad] Endereço:Laboratory for Molecular Neuropsychiatry, Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, Croatia.
[Ti] Título:Effects of acute and chronic administration of neurosteroid dehydroepiandrosterone sulfate on neuronal excitability in mice.
[So] Source:Drug Des Devel Ther;10:1201-15, 2016.
[Is] ISSN:1177-8881
[Cp] País de publicação:New Zealand
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Neurosteroid dehydroepiandrosterone sulfate (DHEAS) has been associated with important brain functions, including neuronal survival, memory, and behavior, showing therapeutic potential in various neuropsychiatric and cognitive disorders. However, the antagonistic effects of DHEAS on γ-amino-butyric acidA receptors and its facilitatory action on glutamatergic neurotransmission might lead to enhanced brain excitability and seizures and thus limit DHEAS therapeutic applications. The aim of this study was to investigate possible age and sex differences in the neuronal excitability of the mice following acute and chronic DHEAS administration. METHODS: DHEAS was administered intraperitoneally in male and female adult and old mice either acutely or repeatedly once daily for 4 weeks in a 10 mg/kg dose. To investigate the potential proconvulsant properties of DHEAS, we studied the effects of acute and chronic DHEAS treatment on picrotoxin-, pentylentetrazole-, and N-methyl-D-aspartate-induced seizures in mice. The effects of acute and chronic DHEAS administration on the locomotor activity, motor coordination, and body weight of the mice were also studied. We also investigated the effects of DHEAS treatment on [(3)H]flunitrazepam binding to the mouse brain membranes. RESULTS: DHEAS did not modify the locomotor activity, motor coordination, body weight, and brain [(3)H]flunitrazepam binding of male and female mice. The results failed to demonstrate significant effects of single- and long-term DHEAS treatment on the convulsive susceptibility in both adult and aged mice of both sexes. However, small but significant changes regarding sex differences in the susceptibility to seizures were observed following DHEAS administration to mice. CONCLUSION: Although our findings suggest that DHEAS treatment might be safe for various potential therapeutic applications in adult as well as in old age, they also support subtle interaction of DHEAS with male and female hormonal status, which may underline observed sex differences in the relationship between DHEAS and various health outcomes.
[Mh] Termos MeSH primário: Encéfalo/efeitos dos fármacos
Sulfato de Desidroepiandrosterona/farmacologia
Atividade Motora/efeitos dos fármacos
Neurônios/efeitos dos fármacos
[Mh] Termos MeSH secundário: Fatores Etários
Animais
Encéfalo/metabolismo
Sulfato de Desidroepiandrosterona/administração & dosagem
Esquema de Medicação
Feminino
Flunitrazepam/metabolismo
Masculino
Camundongos
Camundongos Endogâmicos CBA
Neurônios/metabolismo
Convulsões/etiologia
Fatores Sexuais
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
57B09Q7FJR (Dehydroepiandrosterone Sulfate); 620X0222FQ (Flunitrazepam)
[Em] Mês de entrada:1610
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160407
[St] Status:MEDLINE
[do] DOI:10.2147/DDDT.S102102


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[PMID]:27013620
[Au] Autor:Vindenes V; Strand DH; Koksæter P; Gjerde H
[Ad] Endereço:Division of Forensic Sciences, Norwegian Institute of Public Health, PO Box 4404 Nydalen, NO-0403 Oslo, Norway Norwegian Centre for Addiction Research (SERAF), University of Oslo, PO Box 1039, Blindern, NO-0315 Oslo, Norway vigdis.vindenes@fhi.no.
[Ti] Título:Detection of Nitrobenzodiazepines and Their 7-Amino Metabolites in Oral Fluid.
[So] Source:J Anal Toxicol;40(4):310-2, 2016 May.
[Is] ISSN:1945-2403
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Clonazepam, nitrazepam and flunitrazepam are frequently used benzodiazepines, both as prescribed medication and as drugs of abuse. Little is, however, known about how these drugs are excreted in oral fluid. It has been claimed that the parent drugs are more likely to be detected in oral fluid than the 7-amino metabolites. The aim of this study was to investigate whether the parent drugs or the 7-amino metabolites of the nitrobenzodiazepines were most frequently detected in authentic oral fluid samples. Oral fluid samples were collected from patients undergoing opioid maintenance treatment. Cases where clonazepam, nitrazepam, flunitrazepam and/or their metabolites were detected were included. The samples were collected using the Intercept Oral Specimen Collection Device. A cutoff concentration of 1 nM (∼0.3 ng/mL) in oral fluid-buffer mixture was applied for all the substances. A total of 1,001 oral fluid samples were positive for clonazepam and/or 7-aminoclonazepam; both substances were detected in 707 samples, only the parent drug in 64 cases and only the metabolite in 230 cases. For nitrazepam, both substances were detected in 139 samples; only the parent drug in 16 cases and only the metabolite in 56 cases. Flunitrazepam only was not detected in any sample; both substances were detected in one of these cases, and only the metabolite in three cases. This study revealed that 7-amino metabolites were more likely to be detected in oral fluid than the parent drugs.
[Mh] Termos MeSH primário: Benzodiazepinas/análise
Saliva/química
[Mh] Termos MeSH secundário: Benzodiazepinas/metabolismo
Clonazepam/análogos & derivados
Clonazepam/análise
Flunitrazepam/análise
Seres Humanos
Nitrazepam/análise
Tratamento de Substituição de Opiáceos
Detecção do Abuso de Substâncias/métodos
Espectrometria de Massas em Tandem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
12794-10-4 (Benzodiazepines); 17D6640Q7Y (7-aminoclonazepam); 5PE9FDE8GB (Clonazepam); 620X0222FQ (Flunitrazepam); 9CLV70W7HS (Nitrazepam)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170119
[Lr] Data última revisão:
170119
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160326
[St] Status:MEDLINE
[do] DOI:10.1093/jat/bkw020


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[PMID]:26634646
[Au] Autor:Famiglini G; Termopoli V; Palma P; Cappiello A
[Ad] Endereço:Department SPeA, LC-MS Laboratory, University of Urbino Carlo Bo, Urbino, Italy.
[Ti] Título:Liquid chromatography-electron ionization tandem mass spectrometry with the Direct-EI interface in the fast determination of diazepam and flunitrazepam in alcoholic beverages.
[So] Source:Electrophoresis;37(7-8):1048-54, 2016 Apr.
[Is] ISSN:1522-2683
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:This is the first application based on electron ionization (EI) using a Direct-EI LC interface and MS/MS to detect unequivocally target compounds in a very small real sample. The determination and quantification of benzodiazepines in very small residues of beverages, collected at the scene of drug-facilitated crimes are mandatory in legal procedures. A specific and sensitive analytical instrumentation is needed, involving little or no sample preparation. Here, a direct flow injection analysis of alcoholic beverages spiked with commercially available drugs containing diazepam and flunitrazepam is presented. The method proposed is very fast and requires neither sample preparation nor chromatographic separation. Linearity (R(2) ) was between 0.9977 and 0.9992; LOD and LOQ spanned from 0.01 to 0.02 ng/µL and from 0.1 to 0.5 ng/µL, respectively; intra- and interday repeatabilities were between 1 and 8%. No matrix effects were observed from the comparison of the linear regression curves obtained in real fortified samples and in pure ethanol. Vodka, whisky, and white wine specimens were fortified with commercial drugs, Valium(®) and Rohypnol(®) , at two different concentrations (20 and 50 ng/µL) to simulate the typical amounts found in adulterated real samples and analyzed to demonstrate the method applicability to forensic analyses.
[Mh] Termos MeSH primário: Bebidas Alcoólicas/análise
Cromatografia Líquida/métodos
Diazepam/análise
Flunitrazepam/análise
Espectrometria de Massas por Ionização por Electrospray/métodos
Espectrometria de Massas em Tandem/métodos
[Mh] Termos MeSH secundário: Cromatografia Líquida/instrumentação
Desenho de Equipamento
Limite de Detecção
Modelos Lineares
Reprodutibilidade dos Testes
Espectrometria de Massas por Ionização por Electrospray/instrumentação
Espectrometria de Massas em Tandem/instrumentação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
620X0222FQ (Flunitrazepam); Q3JTX2Q7TU (Diazepam)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151205
[St] Status:MEDLINE
[do] DOI:10.1002/elps.201500517


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[PMID]:26173614
[Au] Autor:Hasegawa K; Wurita A; Minakata K; Gonmori K; Nozawa H; Yamagishi I; Watanabe K; Suzuki O
[Ad] Endereço:Department of Legal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan. Electronic address: 07484771@hama-med.ac.jp.
[Ti] Título:Postmortem distribution of flunitrazepam and its metabolite 7-aminoflunitrazepam in body fluids and solid tissues in an autopsy case: Usefulness of bile for their detection.
[So] Source:Leg Med (Tokyo);17(5):394-400, 2015 Sep.
[Is] ISSN:1873-4162
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:We experienced an autopsy case of a woman in her 70s, in which the direct cause of her death was judged as asphyxia due to the occlusion of food in the trachea. The postmortem interval was estimated at about 2days. The specimens dealt with were femoral vein blood, right heart blood, left heart blood, bile, brain, lung, heart muscle, liver, spleen, kidney, pancreas, skeletal muscle, and adipose tissue. By tentative drug screening, we found a high concentration of 7-aminoflunitrazepam in the femoral vein blood, which lead us to examine the postmortem distribution of flunitrazepam and its metabolite 7-aminoflunitrazepam in her body fluids and solid tissues. The extraction of flunitrazepam, 7-aminoflunitrazepam and internal standard nimetazepam was performed by a modified QuEChERS method, followed by the analysis by liquid chromatography-tandem mass spectrometry. Because this study included various kinds of human matrices with quite different properties, we used the standard additional method to overcome the matrix effects. The concentration of 7-aminoflunitrazepam were generally much higher than those of the parent drug flunitrazepam for most specimens except for the adipose tissue, showing that flunitrazepam is readily metabolized to its 7-amino metabolite after absorption into the body both antemortem and postmortem. The outstandingly highest concentration of 7-animoflunitrazepam was found in the bile, followed by the kidney, pancreas, left heart blood, spleen and liver. Although a majority of flunitrazepam was converted to 7-aminoflunitrazepam, the flunitrazepam concentration was highest in the pancreas, followed by the spleen, bile, left heart blood, and brain. In contrast to the results on synthetic cannabinoids, the levels of flunitrazepam and 7-animoflunitrazepam in the adipose tissue were relatively low. The present study showed that the bile may be a useful specimen for detection of unchanged benzodiazepines/their metabolites to be collected at autopsy.
[Mh] Termos MeSH primário: Bile/química
Flunitrazepam/análogos & derivados
Flunitrazepam/análise
[Mh] Termos MeSH secundário: Tecido Adiposo/química
Idoso
Autopsia
Líquidos Corporais/química
Cromatografia Líquida
Feminino
Flunitrazepam/envenenamento
Homicídio
Seres Humanos
Mudanças Depois da Morte
Espectrometria de Massas em Tandem
Fatores de Tempo
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
620X0222FQ (Flunitrazepam); 7T03QW0G7C (7-aminoflunitrazepam)
[Em] Mês de entrada:1607
[Cu] Atualização por classe:161125
[Lr] Data última revisão:
161125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150716
[St] Status:MEDLINE


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[PMID]:26027828
[Au] Autor:Tsutsui R; Shinomiya K; Sendo T; Kitamura Y; Kamei C
[Ad] Endereço:Department of Clinical Pharmacy, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University.
[Ti] Título:Effects of the 5-HT(1A) Receptor Agonist Tandospirone on ACTH-Induced Sleep Disturbance in Rats.
[So] Source:Biol Pharm Bull;38(6):884-8, 2015.
[Is] ISSN:1347-5215
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:The aim of this study was to compare the effect of the serotonin (5-HT)1A receptor agonist tandospirone versus that of the benzodiazepine hypnotic flunitrazepam in a rat model of long-term adrenocorticotropic hormone (ACTH)-induced sleep disturbance. Rats implanted with electrodes for recording electroencephalogram and electromyogram were injected with ACTH once daily at a dose of 100 µg/rat. Administration of ACTH for 10 d caused a significant increase in sleep latency, decrease in non-rapid eye movement (non-REM) sleep time, and increase in wake time. Tandospirone caused a significant decrease in sleep latency and increase in non-REM sleep time in rats treated with ACTH. The effect of tandospirone on sleep patterns was antagonized by the 5-HT1A receptor antagonist WAY-100635. In contrast, flunitrazepam had no significant effect on sleep parameters in ACTH-treated rats. These results clearly indicate that long-term administration of ACTH causes sleep disturbance, and stimulating the 5-HT1A receptor by tandospirone may be efficacious for improving sleep in cases in which benzodiazepine hypnotics are ineffective.
[Mh] Termos MeSH primário: Hipnóticos e Sedativos/uso terapêutico
Isoindóis/uso terapêutico
Piperazinas/uso terapêutico
Pirimidinas/uso terapêutico
Receptor 5-HT1A de Serotonina/metabolismo
Agonistas de Receptores 5-HT1 de Serotonina/uso terapêutico
Transtornos do Sono-Vigília/tratamento farmacológico
Sono/efeitos dos fármacos
[Mh] Termos MeSH secundário: Hormônio Adrenocorticotrópico
Animais
Modelos Animais de Doenças
Eletroencefalografia
Flunitrazepam/farmacologia
Flunitrazepam/uso terapêutico
Moduladores GABAérgicos/farmacologia
Moduladores GABAérgicos/uso terapêutico
Hipnóticos e Sedativos/farmacologia
Isoindóis/farmacologia
Masculino
Piperazinas/farmacologia
Piridinas/farmacologia
Pirimidinas/farmacologia
Ratos Wistar
Serotonina/metabolismo
Agonistas de Receptores 5-HT1 de Serotonina/farmacologia
Antagonistas da Serotonina/farmacologia
Transtornos do Sono-Vigília/induzido quimicamente
Transtornos do Sono-Vigília/metabolismo
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (GABA Modulators); 0 (Hypnotics and Sedatives); 0 (Isoindoles); 0 (Piperazines); 0 (Pyridines); 0 (Pyrimidines); 0 (Serotonin 5-HT1 Receptor Agonists); 0 (Serotonin Antagonists); 112692-38-3 (Receptor, Serotonin, 5-HT1A); 190230I669 (tandospirone); 333DO1RDJY (Serotonin); 620X0222FQ (Flunitrazepam); 71IH826FEG (N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide); 9002-60-2 (Adrenocorticotropic Hormone)
[Em] Mês de entrada:1602
[Cu] Atualização por classe:150601
[Lr] Data última revisão:
150601
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150602
[St] Status:MEDLINE
[do] DOI:10.1248/bpb.b14-00887



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