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[PMID]:28829722
[Au] Autor:Brodin T; Nordling J; Lagesson A; Klaminder J; Hellström G; Christensen B; Fick J
[Ad] Endereço:a Department of Ecology and Environmental Science , Umeå University , Umeå , Sweden.
[Ti] Título:Environmental relevant levels of a benzodiazepine (oxazepam) alters important behavioral traits in a common planktivorous fish, (Rutilus rutilus).
[So] Source:J Toxicol Environ Health A;80(16-18):963-970, 2017.
[Is] ISSN:1528-7394
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Environmental pollution by pharmaceuticals is increasingly recognized as a major threat to aquatic ecosystems worldwide. A complex mix of pharmaceuticals enters waterways via treated wastewater effluent and many remain biochemically active after the drugs reach aquatic systems. However, to date little is known regarding the ecological effects that might arise following pharmaceutical contamination of aquatic environments. One group of particular concern is behaviorally modifying pharmaceuticals as seemingly minor changes in behavior may initiate marked ecological consequences. The aim of this study was to examine the influence of a benzodiazepine anxiolytic drug (oxazepam) on key behavioral traits in wild roach (Rutilus rutilus) at concentrations similar to those encountered in effluent surface waters. Roach exposed to water with high concentrations of oxazepam (280 µg/L) exhibited increased boldness, while roach at low treatment (0.84 µg/L) became bolder and more active compared to control fish. Our results reinforce the notion that anxiolytic drugs may be affecting fish behavior in natural systems, emphasizing the need for further research on ecological impacts of pharmaceuticals in aquatic systems and development of new tools to incorporate ecologically relevant behavioral endpoints into ecotoxicological risk assessment.
[Mh] Termos MeSH primário: Comportamento Animal/efeitos dos fármacos
Cyprinidae/fisiologia
Exposição Ambiental/efeitos adversos
Oxazepam/toxicidade
Poluentes Químicos da Água/toxicidade
[Mh] Termos MeSH secundário: Animais
Ansiolíticos/toxicidade
Determinação de Ponto Final
Águas Residuais/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Anxiety Agents); 0 (Waste Water); 0 (Water Pollutants, Chemical); 6GOW6DWN2A (Oxazepam)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170823
[St] Status:MEDLINE
[do] DOI:10.1080/15287394.2017.1352214


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[PMID]:28445845
[Au] Autor:Mináriková M; Fojtikova V; Vyskocilová E; Sedlácek J; Sikut M; Borek-Dohalska L; Stiborová M; Martinkova M
[Ad] Endereço:Department of Biochemistry, Faculty of Science, Charles University, Hlavova (Albertov) 2030-8, Prague 2, Czech Republic.
[Ti] Título:The capacity and effectiveness of diosmectite and charcoal in trapping the compounds causing the most frequent intoxications in acute medicine: A comparative study.
[So] Source:Environ Toxicol Pharmacol;52:214-220, 2017 Jun.
[Is] ISSN:1872-7077
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The aim of the study was to compare the adsorption ability of two adsorbent materials, namely diosmectite and activated charcoal towards selected model compounds that are most commonly involved in acute intoxication. Eleven model compounds were selected: acetylsalicylic acid, α-amanitin, amlodipine, digoxin, phenobarbital, ibuprofen, imipramine, carbamazepine, oxazepam, promethazine, and theophylline. Of the tested compounds, promethazine and imipramine were the most effectively adsorbed to diosmectite. Their adsorption to diosmectite (0.356±0.029mg promethazine/mg diosmectite and 0.354±0.019mg imipramine/mg diosmectite, respectively) was significantly higher than their adsorption to activated charcoal. The effect of temperature and pH on the adsorption efficiencies was also evaluated. In the case of experiments with mixture of both adsorbents, they mostly behaved in a solution independently or in a slightly antagonistic way. Using various methods such as N adsorption and thermogravimetric analysis, the structure and texture of diosmectite and activated charcoal were attained.
[Mh] Termos MeSH primário: Antídotos/química
Carvão Vegetal/química
Envenenamento/prevenção & controle
Silicatos/química
[Mh] Termos MeSH secundário: Adsorção
Alfa-Amanitina/química
Anlodipino/química
Aspirina/química
Carbamazepina/química
Digoxina/química
Ibuprofeno/química
Imipramina/química
Oxazepam/química
Fenobarbital/química
Prometazina/química
Teofilina/química
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Alpha-Amanitin); 0 (Antidotes); 0 (Silicates); 16291-96-6 (Charcoal); 1J444QC288 (Amlodipine); 33CM23913M (Carbamazepine); 6GOW6DWN2A (Oxazepam); 73K4184T59 (Digoxin); A3N5ZCN45C (Smectite); C137DTR5RG (Theophylline); FF28EJQ494 (Promethazine); OGG85SX4E4 (Imipramine); R16CO5Y76E (Aspirin); WK2XYI10QM (Ibuprofen); YQE403BP4D (Phenobarbital)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170427
[St] Status:MEDLINE


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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]:28242100
[Au] Autor:Sacre L; Ali SM; Villa A; Jouffroy R; Raphalen JH; Garnier R; Baud FJ
[Ad] Endereço:UMR 8257 cognitive action group, Paris Descartes university, 45, rue des Saints-Pères, 75270 Paris cedex 06, France; Paris poison control centre, hôpital Fernand-Widal, 200, rue du Faubourg-Saint-Denis, 75010 Paris, France. Electronic address: lynnsacre@hotmail.com.
[Ti] Título:Toxicodynetics in nordiazepam and oxazepam overdoses.
[So] Source:Ann Pharm Fr;75(3):163-171, 2017 May.
[Is] ISSN:0003-4509
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: Toxicodynetics aims at defining the time-course of major clinical events in drug overdose. We report the toxicodynetics in mono-intoxications with oxazepam and nordiazepam. METHODS: Cases of oxazepam or nordiazepam overdoses collected at the Paris poison control centre from 1999 to 2014 on the basis of self-report. A particular attention was paid to eliminate the concomitant alcohol or psychotropic co-ingestions. The toxicodynetic parameters were assessed as previously described. Results are expressed using 10-90 percentiles. In adults, the dose was normalized (TI, toxic Index) by dividing the supposed ingested dose by the maximal recommended dose. RESULTS: Two hundred and fifty-one and 74 cases of oxazepam and nordiazepam poisonings were included, respectively. The Emax for oxazepam and nordiazepam were sleepiness or obtundation in 106 and 36 cases, respectively. Coma was used to qualify only one oxazepam overdose. The median delay in onset of the Emax was 1.5h (0.33-15) in nordiazepam and 4h (0.5-15) in oxazepam overdose. In both overdoses, the onset of Emax occurred on an "on-off" mode. In adults, the greatest TIs in nordiazepam and oxazepam overdoses were 45 and 26.7, respectively. The TI in the oxazepam-induced coma was 26.7, the largest dose. CONCLUSION: Data collected in PCC allow determining a number of toxicodynetic parameters. Toxicodynetics showed that nordiazepam is not a cause of coma even in large overdose while oxazepam causes coma only at a very high dose. Deep coma in nordiazepam overdose whatever the dose and deep coma in overdose with oxazepam involving TI less than 20 result from unrecognized drug-drug interaction.
[Mh] Termos MeSH primário: Overdose de Drogas/metabolismo
Moduladores GABAérgicos/efeitos adversos
Moduladores GABAérgicos/farmacocinética
Nordazepam/efeitos adversos
Nordazepam/farmacocinética
Oxazepam/efeitos adversos
Oxazepam/farmacocinética
Toxicocinética
[Mh] Termos MeSH secundário: Adolescente
Adulto
Envelhecimento/metabolismo
Depressores do Sistema Nervoso Central/efeitos adversos
Criança
Pré-Escolar
Etanol/efeitos adversos
Feminino
Seres Humanos
Masculino
Meia-Idade
Estudos Retrospectivos
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (Central Nervous System Depressants); 0 (GABA Modulators); 3K9958V90M (Ethanol); 67220MCM01 (Nordazepam); 6GOW6DWN2A (Oxazepam)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170814
[Lr] Data última revisão:
170814
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170301
[St] Status:MEDLINE


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[PMID]:28160051
[Au] Autor:El Balkhi S; Chaslot M; Picard N; Dulaurent S; Delage M; Mathieu O; Saint-Marcoux F
[Ad] Endereço:Department of Pharmacology, Service de pharmacologie, toxicologie et pharmacovigilance, CHU de Limoges, Limoges University Hospital, 2 Ave Martin Luther King, 87042, Limoges Cedex, France. souleiman.elbalkhi@chu-limoges.fr.
[Ti] Título:Characterization and identification of eight designer benzodiazepine metabolites by incubation with human liver microsomes and analysis by a triple quadrupole mass spectrometer.
[So] Source:Int J Legal Med;131(4):979-988, 2017 Jul.
[Is] ISSN:1437-1596
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Designer benzodiazepines (DBZDs) have become of particular importance in the past few years. The metabolite monitoring of DBZD in biological fluids could be of great interest in clinical and forensic toxicology. However, DBZD metabolites are not known or not commercially available. The identification of some DBZD metabolites has been mostly explored by self-administration studies or by in vitro studies followed by high-resolution mass spectrometry. The question arose whether a unit resolution instrument could be efficient enough to allow the identification of DBZD metabolites. In this study, we used an in vitro experiment where eight DBZDs (diclazepam, flubromazepam, etizolam, deschloroetizolam, flubromazolam, nifoxipam, meclonazepam and clonazolam) were incubated with human liver microsomes (HLMs) and metabolite identification was carried out by using a UHPLC coupled to a QTRAP triple quadrupole linear iontrap tandem mass spectrometer system. Post-mortem samples obtained from a real poisoning case, involving deschloroetizolam and diclazepam, were also analysed and discussed. Our study using HLM allowed the identification of 26 metabolites of the 8 DBZDs. These were denitro-, mono- or di-hydroxylated and desmethyl metabolites. In the forensic case, diclazepam was not detected whereas its metabolites (lormetazepam and lorazepam) were present at high concentrations in urine. We also identified hydroxy-deschloroetizolam in urine, while the parent compound was not detected in this matrix. This supports the approach that LC coupled to a simple QTRAP could be used by laboratories to identify other not-known/not-commercialized new psychoactive substance (NPS) metabolites.
[Mh] Termos MeSH primário: Benzodiazepinas/química
Drogas Desenhadas/química
Microssomos Hepáticos/química
[Mh] Termos MeSH secundário: Adulto
Benzodiazepinas/análise
Cromatografia Líquida
Drogas Desenhadas/análise
Seres Humanos
Lorazepam/análogos & derivados
Lorazepam/urina
Masculino
Oxazepam/urina
Transtornos Relacionados ao Uso de Substâncias/urina
Espectrometria de Massas em Tandem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Designer Drugs); 12794-10-4 (Benzodiazepines); 6GOW6DWN2A (Oxazepam); GU56C842ZA (lormetazepam); O26FZP769L (Lorazepam)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170205
[St] Status:MEDLINE
[do] DOI:10.1007/s00414-017-1541-6


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[PMID]:27981403
[Au] Autor:Mazzitelli JY; Bonnafe E; Klopp C; Escudier F; Geret F
[Ad] Endereço:Biochimie et Toxicologie des Substances Bioactives (BTSB), EA7417, Université de Toulouse, INU Champollion, Albi, France. jyves.maz@gmail.com.
[Ti] Título:De novo transcriptome sequencing and analysis of freshwater snail (Radix balthica) to discover genes and pathways affected by exposure to oxazepam.
[So] Source:Ecotoxicology;26(1):127-140, 2017 Jan.
[Is] ISSN:1573-3017
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Pharmaceuticals are increasingly found in aquatic ecosystems due to the non-efficiency of waste water treatment plants. Therefore, aquatic organisms are frequently exposed to a broad diversity of pharmaceuticals. Freshwater snail Radix balthica has been chosen as model to study the effects of oxazepam (psychotropic drug) on developmental stages ranging from trochophore to hatching. In order to provide a global insight of these effects, a transcriptome deep sequencing has been performed on exposed embryos. Eighteen libraries were sequenced, six libraries for three conditions: control, exposed to the lowest oxazepam concentration with a phenotypic effect (delayed hatching) (TA) and exposed to oxazepam concentration found in freshwater (TB). A total of 39,759,772 filtered raw reads were assembled into 56,435 contigs having a mean length of 1579.68 bp and mean depth of 378.96 reads. 44.91% of the contigs have at least one annotation. The differential expression analysis between the control condition and the two exposure conditions revealed 146 contigs differentially expressed of which 144 for TA and two for TB. 34.0% were annotated with biological function. There were four mainly impacted processes: two cellular signalling systems (Notch and JNK) and two biosynthesis pathways (Polyamine and Catecholamine pathways). This work reports a large-scale analysis of differentially transcribed genes of R. balthica exposed to oxazepam during egg development until hatching. In addition, these results enriched the de novo database of potential ecotoxicological models.
[Mh] Termos MeSH primário: Expressão Gênica/efeitos dos fármacos
Oxazepam/toxicidade
Psicotrópicos/toxicidade
Caramujos/genética
[Mh] Termos MeSH secundário: Animais
Água Doce
Perfilação da Expressão Gênica
Sequenciamento de Nucleotídeos em Larga Escala
Transcriptoma
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Psychotropic Drugs); 6GOW6DWN2A (Oxazepam)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:171019
[Lr] Data última revisão:
171019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161217
[St] Status:MEDLINE
[do] DOI:10.1007/s10646-016-1748-1


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[PMID]:27862608
[Au] Autor:Salvatore S; Røislien J; Baz-Lomba JA; Bramness JG
[Ad] Endereço:Norwegian Centre for Addiction Research, University of Oslo, Oslo, Norway.
[Ti] Título:Assessing prescription drug abuse using functional principal component analysis (FPCA) of wastewater data.
[So] Source:Pharmacoepidemiol Drug Saf;26(3):320-326, 2017 Mar.
[Is] ISSN:1099-1557
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Wastewater-based epidemiology is an alternative method for estimating the collective drug use in a community. We applied functional data analysis, a statistical framework developed for analysing curve data, to investigate weekly temporal patterns in wastewater measurements of three prescription drugs with known abuse potential: methadone, oxazepam and methylphenidate, comparing them to positive and negative control drugs. METHODS: Sewage samples were collected in February 2014 from a wastewater treatment plant in Oslo, Norway. The weekly pattern of each drug was extracted by fitting of generalized additive models, using trigonometric functions to model the cyclic behaviour. From the weekly component, the main temporal features were then extracted using functional principal component analysis. Results are presented through the functional principal components (FPCs) and corresponding FPC scores. RESULTS: Clinically, the most important weekly feature of the wastewater-based epidemiology data was the second FPC, representing the difference between average midweek level and a peak during the weekend, representing possible recreational use of a drug in the weekend. Estimated scores on this FPC indicated recreational use of methylphenidate, with a high weekend peak, but not for methadone and oxazepam. CONCLUSION: The functional principal component analysis uncovered clinically important temporal features of the weekly patterns of the use of prescription drugs detected from wastewater analysis. This may be used as a post-marketing surveillance method to monitor prescription drugs with abuse potential. Copyright © 2016 John Wiley & Sons, Ltd.
[Mh] Termos MeSH primário: Uso Indevido de Medicamentos sob Prescrição/estatística & dados numéricos
Esgotos/análise
Transtornos Relacionados ao Uso de Substâncias/epidemiologia
Águas Residuais/análise
[Mh] Termos MeSH secundário: Monitoramento Ambiental/métodos
Seres Humanos
Metadona/administração & dosagem
Metilfenidato/administração & dosagem
Modelos Teóricos
Noruega/epidemiologia
Oxazepam/administração & dosagem
Análise de Componente Principal
Detecção do Abuso de Substâncias/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Sewage); 0 (Waste Water); 207ZZ9QZ49 (Methylphenidate); 6GOW6DWN2A (Oxazepam); UC6VBE7V1Z (Methadone)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171004
[Lr] Data última revisão:
171004
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161119
[St] Status:MEDLINE
[do] DOI:10.1002/pds.4127


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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]:27658223
[Au] Autor:Heynen M; Backström T; Fick J; Jonsson M; Klaminder J; Brodin T
[Ad] Endereço:Department of Ecology and Environmental Science, Umeå University, Sweden; Department of Chemistry, Umeå University, Sweden. Electronic address: martina_heynen@web.de.
[Ti] Título:Home alone-The effects of isolation on uptake of a pharmaceutical contaminant in a social fish.
[So] Source:Aquat Toxicol;180:71-77, 2016 Nov.
[Is] ISSN:1879-1514
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:A wide range of biologically active pharmaceutical residues is present in aquatic systems worldwide. As uptake potential and the risk of effects in aquatic wildlife are directly coupled, the aim of this study was to investigate the relationships between stress by isolation, uptake and effects of the psychiatric pharmaceutical oxazepam in fish. To do this, we measured cortisol levels, behavioral stress responses, and oxazepam uptake under different stress and social conditions, in juvenile perch (Perca fluviatilis) that were either exposed (1.03µgl ) or not exposed to oxazepam. We found single exposed individuals to take up more oxazepam than individuals exposed in groups, likely as a result of stress caused by isolation. Furthermore, the bioconcentration factor (BCF) was significantly negatively correlated with fish weight in both social treatments. We found no effect of oxazepam exposure on body cortisol concentration or behavioral stress response. Most laboratory experiments, including standardized bioconcentration assays, are designed to minimize stress for the test organisms, however wild animals experience stress naturally. Hence, differences in stress levels between laboratory and natural environments can be one of the reasons why predictions from artificial laboratory experiments largely underestimate uptake of oxazepam, and other pharmaceuticals, in the wild.
[Mh] Termos MeSH primário: Oxazepam/farmacocinética
Percas/metabolismo
Isolamento Social
Estresse Psicológico/metabolismo
Poluentes Químicos da Água/farmacocinética
[Mh] Termos MeSH secundário: Animais
Comportamento Animal/efeitos dos fármacos
Biomarcadores/metabolismo
Carga Corporal (Radioterapia)
Hidrocortisona/metabolismo
Oxazepam/toxicidade
Poluentes Químicos da Água/toxicidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Water Pollutants, Chemical); 6GOW6DWN2A (Oxazepam); WI4X0X7BPJ (Hydrocortisone)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170917
[Lr] Data última revisão:
170917
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160923
[St] Status:MEDLINE


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[PMID]:27485488
[Au] Autor:Spence AL; Guerin GF; Goeders NE
[Ad] Endereço:Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center - Shreveport, Shreveport, LA 71130, United States. Electronic address: aspen4@lsuhsc.edu.
[Ti] Título:The differential effects of alprazolam and oxazepam on methamphetamine self-administration in rats.
[So] Source:Drug Alcohol Depend;166:209-17, 2016 Sep 01.
[Is] ISSN:1879-0046
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Methamphetamine is the second most commonly used illicit drug in the world, and despite recent attempts by the Drug Enforcement Administration to combat this epidemic, methamphetamine use is still on the rise. As methamphetamine use increases so does polydrug use, particularly that involving methamphetamine and benzodiazepines. The present study was designed to examine the effects of two benzodiazepines on methamphetamine self-administration. METHODS: Five doses of methamphetamine (0.0075, 0.015, 0.03, 0.09, and 0.12mg/kg/infusion) were tested, producing an inverted U-shaped dose-response curve. Rats were then pretreated with oxazepam, alprazolam, or vehicle prior to methamphetamine self-administration. To determine if the effects of these drugs were due to the GABAA receptor and/or translocator protein (TSPO), we also pretreated rats with an antagonist for the benzodiazepine-binding site on the GABAA receptor (i.e., flumazenil) and a TSPO antagonist (i.e., PK11195) prior to alprazolam or oxazepam administration. RESULTS: Oxazepam significantly reduced methamphetamine self-administration as demonstrated by a downward shift of the dose-response curve. In contrast, alprazolam significantly enhanced methamphetamine self-administration as evidenced by a leftward shift of the dose-response curve. Flumazenil completely blocked the effects of alprazolam on methamphetamine self-administration. When administered individually, both flumazenil and PK11195 partially reversed the effects of oxazepam on methamphetamine self-administration. However, when these two antagonists were combined, the effects of oxazepam were completely reversed. CONCLUSIONS: The GABAA receptor is responsible for the alprazolam-induced enhancement of methamphetamine self-administration, while the activation of both the GABAA receptor and TSPO are responsible for the oxazepam-induced reduction of methamphetamine self-administration.
[Mh] Termos MeSH primário: Alprazolam/farmacologia
Transtornos Relacionados ao Uso de Anfetaminas/psicologia
Metanfetamina
Oxazepam/farmacologia
Autoadministração/psicologia
[Mh] Termos MeSH secundário: Animais
Relação Dose-Resposta a Droga
Flumazenil/farmacologia
Isoquinolinas/farmacologia
Masculino
Metanfetamina/farmacologia
Pré-Medicação
Ratos
Ratos Wistar
Receptores de GABA-A/efeitos dos fármacos
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Isoquinolines); 0 (Receptors, GABA-A); 40P7XK9392 (Flumazenil); 44RAL3456C (Methamphetamine); 6GOW6DWN2A (Oxazepam); YNF83VN1RL (PK 11195); YU55MQ3IZY (Alprazolam)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160804
[St] Status:MEDLINE



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