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[PMID]:26282513
[Au] Autor:Jeong YD; Kim MK; Suh SI; In MK; Kim JY; Paeng KJ
[Ad] Endereço:Department of Chemistry, Yonsei University, Republic of Korea.
[Ti] Título:Rapid determination of benzodiazepines, zolpidem and their metabolites in urine using direct injection liquid chromatography-tandem mass spectrometry.
[So] Source:Forensic Sci Int;257:84-92, 2015 Dec.
[Is] ISSN:1872-6283
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:Benzodiazepines and zolpidem are generally prescribed as sedative, hypnotics, anxiolytics or anticonvulsants. These drugs, however, are frequently misused in drug-facilitated crime. Therefore, a rapid and simple liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed for identification and quantification of benzodiazepines, zolpidem and their metabolites in urine using deuterium labeled internal standards (IS). Urine samples (120 µL) mixed with 80 µL of the IS solution were centrifuged. An aliquot (5 µL) of the sample solution was directly injected into the LC-MS/MS system for analysis. The mobile phases consisted of water and acetonitrile containing 2mM ammonium trifluoroacetate and 0.2% acetic acid. The analytical column was a Zorbax SB-C18 (100 mm × 2.1 mm i.d., 3.5 µm, Agilent). The separation and detection of 18 analytes were achieved within 10 min. Calibration curves were linear over the concentration ranges of 0.5-20 ng/mL (zolpidem), 1.0-40 ng/mL (flurazepam and temazepam), 2.5-100 ng/mL (7-aminoclonazepam, 1-hydroxymidazolam, midazolam, flunitrazepam and alprazolam), 5.0-200 ng/mL (zolpidem phenyl-4-carboxylic acid, α-hydroxyalprazolam, oxazepam, nordiazepam, triazolam, diazepam and α-hydroxytriazolam), 10-400 ng/mL (lorazepam and desalkylflurazepam) and 10-100 ng/mL (N-desmethylflunitrazepam) with the coefficients of determination (r(2)) above 0.9971. The dilution integrity of the analytes was examined for supplementation of short linear range. Dilution precision and accuracy were tested using two, four and ten-folds dilutions and they ranged from 3.7 to 14.4% and -12.8 to 12.5%, respectively. The process efficiency for this method was 63.0-104.6%. Intra- and inter-day precisions were less than 11.8% and 9.1%, while intra- and inter-day accuracies were less than -10.0 to 8.2%, respectively. The lower limits of quantification were lower than 10 ng/mL for each analyte. The applicability of the developed method was successfully verified with human urine samples from drug users (n=21). Direct urine sample injection and optimized mobile phases were introduced for simple sample preparation and high-sensitivity with the desired separation.
[Mh] Termos MeSH primário: Benzodiazepinas/urina
Cromatografia Líquida/métodos
Hipnóticos e Sedativos/urina
Piridinas/urina
Espectrometria de Massas em Tandem/métodos
[Mh] Termos MeSH secundário: Alprazolam/análogos & derivados
Alprazolam/urina
Flurazepam/análogos & derivados
Flurazepam/urina
Toxicologia Forense/métodos
Seres Humanos
Limite de Detecção
Triazolam/análogos & derivados
Triazolam/urina
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Hypnotics and Sedatives); 0 (Pyridines); 12794-10-4 (Benzodiazepines); 1HM943223R (Triazolam); 37115-43-8 (alpha-hydroxyalprazolam); 37115-45-0 (alpha-hydroxytriazolam); 7K383OQI23 (zolpidem); BUJ3JOD7XF (didesethylflurazepam); IHP475989U (Flurazepam); YU55MQ3IZY (Alprazolam)
[Em] Mês de entrada:1609
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150819
[St] Status:MEDLINE


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[PMID]:25839897
[Au] Autor:Blednov YA; Benavidez JM; Black M; Mayfield J; Harris RA
[Ad] Endereço:Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, TX 78712, USA.
[Ti] Título:Role of interleukin-1 receptor signaling in the behavioral effects of ethanol and benzodiazepines.
[So] Source:Neuropharmacology;95:309-20, 2015 Aug.
[Is] ISSN:1873-7064
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Gene expression studies identified the interleukin-1 receptor type I (IL-1R1) as part of a pathway associated with a genetic predisposition to high alcohol consumption, and lack of the endogenous IL-1 receptor antagonist (IL-1ra) strongly reduced ethanol intake in mice. Here, we compared ethanol-mediated behaviors in mice lacking Il1rn or Il1r1. Deletion of Il1rn (the gene encoding IL-1ra) increases sensitivity to the sedative/hypnotic effects of ethanol and flurazepam and reduces severity of acute ethanol withdrawal. Conversely, deletion of Il1r1 (the gene encoding the IL-1 receptor type I, IL-1R1) reduces sensitivity to the sedative effects of ethanol and flurazepam and increases the severity of acute ethanol withdrawal. The sedative effects of ketamine and pentobarbital were not altered in the knockout (KO) strains. Ethanol intake and preference were not changed in mice lacking Il1r1 in three different tests of ethanol consumption. Recovery from ethanol-induced motor incoordination was only altered in female mice lacking Il1r1. Mice lacking Il1rn (but not Il1r1) showed increased ethanol clearance and decreased ethanol-induced conditioned taste aversion. The increased ethanol- and flurazepam-induced sedation in Il1rn KO mice was decreased by administration of IL-1ra (Kineret), and pre-treatment with Kineret also restored the severity of acute ethanol withdrawal. Ethanol-induced sedation and withdrawal severity were changed in opposite directions in the null mutants, indicating that these responses are likely regulated by IL-1R1 signaling, whereas ethanol intake and preference do not appear to be solely regulated by this pathway.
[Mh] Termos MeSH primário: Comportamento Animal/efeitos dos fármacos
Benzodiazepinas/farmacologia
Etanol/farmacologia
Hipnóticos e Sedativos/farmacologia
Proteína Antagonista do Receptor de Interleucina 1/metabolismo
Receptores Tipo I de Interleucina-1/metabolismo
[Mh] Termos MeSH secundário: Consumo de Bebidas Alcoólicas/metabolismo
Animais
Aprendizagem da Esquiva/efeitos dos fármacos
Aprendizagem da Esquiva/fisiologia
Comportamento Animal/fisiologia
Feminino
Flurazepam/farmacologia
Proteína Antagonista do Receptor de Interleucina 1/genética
Proteína Antagonista do Receptor de Interleucina 1/farmacologia
Ketamina/farmacologia
Masculino
Camundongos da Linhagem 129
Camundongos Endogâmicos C57BL
Camundongos Knockout
Atividade Motora/efeitos dos fármacos
Atividade Motora/fisiologia
Pentobarbital/farmacologia
Receptores Tipo I de Interleucina-1/genética
Índice de Gravidade de Doença
Síndrome de Abstinência a Substâncias/metabolismo
Percepção Gustatória/efeitos dos fármacos
Percepção Gustatória/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Hypnotics and Sedatives); 0 (IL1R1 protein, mouse); 0 (Il1rn protein, mouse); 0 (Interleukin 1 Receptor Antagonist Protein); 0 (Receptors, Interleukin-1 Type I); 12794-10-4 (Benzodiazepines); 3K9958V90M (Ethanol); 690G0D6V8H (Ketamine); I4744080IR (Pentobarbital); IHP475989U (Flurazepam)
[Em] Mês de entrada:1603
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150404
[St] Status:MEDLINE


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[PMID]:25080584
[Au] Autor:Kerti-Szigeti K; Nusser Z; Eyre MD
[Ad] Endereço:Laboratory of Cellular Neurophysiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest 1083, Hungary.
[Ti] Título:Synaptic GABAA receptor clustering without the γ2 subunit.
[So] Source:J Neurosci;34(31):10219-33, 2014 Jul 30.
[Is] ISSN:1529-2401
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Rapid activation of postsynaptic GABAA receptors (GABAARs) is crucial in many neuronal functions, including the synchronization of neuronal ensembles and controlling the precise timing of action potentials. Although the γ2 subunit is believed to be essential for the postsynaptic clustering of GABAARs, synaptic currents have been detected in neurons obtained from γ2(-/-) mice. To determine the role of the γ2 subunit in synaptic GABAAR enrichment, we performed a spatially and temporally controlled γ2 subunit deletion by injecting Cre-expressing viral vectors into the neocortex of GABAARγ2(77I)lox mice. Whole-cell recordings revealed the presence of miniature IPSCs in Cre(+) layer 2/3 pyramidal cells (PCs) with unchanged amplitudes and rise times, but significantly prolonged decays. Such slowly decaying currents could be evoked in PCs by action potentials in presynaptic fast-spiking interneurons. Freeze-fracture replica immunogold labeling revealed the presence of the α1 and ß3 subunits in perisomatic synapses of cells that lack the γ2 subunit. Miniature IPSCs in Cre(+) PCs were insensitive to low concentrations of flurazepam, providing a pharmacological confirmation of the lack of the γ2 subunit. Receptors assembled from only αß subunits were unlikely because Zn(2+) did not block the synaptic currents. Pharmacological experiments indicated that the αßγ3 receptor, rather than the αßδ, αßε, or αßγ1 receptors, was responsible for the slowly decaying IPSCs. Our data demonstrate the presence of IPSCs and the synaptic enrichment of the α1 and ß3 subunits and suggest that the γ3 subunit is the most likely candidate for clustering GABAARs at synapses in the absence of the γ2 subunit.
[Mh] Termos MeSH primário: Neurônios/fisiologia
Receptores de GABA-A/deficiência
Sinapses/fisiologia
[Mh] Termos MeSH secundário: Animais
Ansiolíticos/farmacologia
Carbolinas/farmacologia
Convulsivantes/farmacologia
Desoxicorticosterona/análogos & derivados
Desoxicorticosterona/farmacologia
Estimulação Elétrica
Feminino
Flurazepam/farmacologia
GABAérgicos/farmacologia
Proteínas de Fluorescência Verde/genética
Proteínas de Fluorescência Verde/metabolismo
Técnicas In Vitro
Potenciais Pós-Sinápticos Inibidores/efeitos dos fármacos
Lisina/análogos & derivados
Lisina/metabolismo
Masculino
Potenciais da Membrana/fisiologia
Camundongos
Camundongos Transgênicos
Neocórtex/citologia
Neurônios/ultraestrutura
Receptores de GABA-A/genética
Sinapses/ultraestrutura
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Anxiety Agents); 0 (Carbolines); 0 (Convulsants); 0 (GABA Agents); 0 (Receptors, GABA-A); 1309288N1J (methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate); 147336-22-9 (Green Fluorescent Proteins); 40GP35YQ49 (Desoxycorticosterone); 4AB717DP4A (tetrahydrodeoxycorticosterone); G6D6147J22 (biocytin); IHP475989U (Flurazepam); K3Z4F929H6 (Lysine)
[Em] Mês de entrada:1409
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140801
[St] Status:MEDLINE
[do] DOI:10.1523/JNEUROSCI.1721-14.2014


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[PMID]:24856286
[Au] Autor:Zhou J; Yamaguchi K; Ohno Y
[Ad] Endereço:Department of Forensic Science, Zhejiang Police College, Hangzhou, PR China; Department of Legal Medicine, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
[Ti] Título:Quantitative analysis of quazepam and its metabolites in human blood, urine, and bile by liquid chromatography-tandem mass spectrometry.
[So] Source:Forensic Sci Int;241:e5-12, 2014 Aug.
[Is] ISSN:1872-6283
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:Quazepam (QZP), which is a long-acting benzodiazepine-type hypnotic, and its 4 metabolites, 2-oxoquazepam, N-desalkyl-2-oxoquazepam (DOQ), 3-hydroxy-2-oxoquazepam (HOQ), and 3-hydroxy-N-desalkyl-2-oxoquazepam, in human blood, urine, and bile were quantitatively analyzed by liquid chromatography-tandem mass spectrometry. The analytes were extracted from blood by protein precipitation followed by solid phase extraction, and from urine and bile by liquid-liquid extraction and cleanup using a PSA solid phase extraction cartridge. This method was applied to a medico-legal autopsy case, in which the deceased had been prescribed QZP approximately 3 weeks before his death. In blood, the concentrations of free DOQ (160±7 ng/mL for heart blood and 181±12 ng/mL for femoral blood) were the highest of all the analytes and in agreement with the concentration at a steady state. This indicates that the deceased consecutively received QZP for at least several days until the concentrations reached approximately the same level as that in the steady state. An extremely high concentration of total HOQ (the sum of conjugated and free HOQ) in bile was also found (56,200±1900 ng/mL). This accumulation of HOQ in bile is probably due to enterohepatic circulation. This study demonstrates that the combination of the concentrations of QZP and its metabolites in biological matrices can provide more information about the amount and frequency of QZP administration.
[Mh] Termos MeSH primário: Benzodiazepinas/análise
Hipnóticos e Sedativos/análise
[Mh] Termos MeSH secundário: Benzodiazepinas/farmacocinética
Benzodiazepinonas/análise
Bile/química
Cromatografia Líquida
Flurazepam/análogos & derivados
Flurazepam/análise
Toxicologia Forense
Seres Humanos
Hipnóticos e Sedativos/farmacocinética
Masculino
Meia-Idade
Estrutura Molecular
Espectrometria de Massas em Tandem
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (3-hydroxy-2-oxoquazepam); 0 (Benzodiazepinones); 0 (Hypnotics and Sedatives); 12794-10-4 (Benzodiazepines); 17617-60-6 (3-hydroxy-N-desalkyl-2-oxoquazepam); 8T62S796K7 (2-oxoquazepam); IHP475989U (Flurazepam); JF8V0828ZI (quazepam); X9U41NXR6M (norflutoprazepam)
[Em] Mês de entrada:1510
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140527
[St] Status:MEDLINE


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[PMID]:24241181
[Au] Autor:Xie HB; Sha Y; Wang J; Cheng MS
[Ad] Endereço:Key Laboratory of Structure-Based Drugs Design and Discovery of Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, 110016, People's Republic of China.
[Ti] Título:Some insights into the binding mechanism of the GABAA receptor: a combined docking and MM-GBSA study.
[So] Source:J Mol Model;19(12):5489-500, 2013 Dec.
[Is] ISSN:0948-5023
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Gamma-aminobutyric type A receptor (GABAAR) is a member of the Cys-loop family of pentameric ligand gated ion channels (pLGICs). It has been identified as a key target for many clinical drugs. In the present study, we construct the structure of human 2α12ß2γ2 GABA(A)R using a homology modeling method. The structures of ten benzodiazepine type drugs and two non-benzodiazepine type drugs were then docked into the potential benzodiazepine binding site on the GABA(A)R. By analyzing the docking results, the critical residues His102 (α1), Phe77 (γ2) and Phe100 (α1) were identified in the binding site. To gain insight into the binding affinity, molecular dynamics (MD) simulations were performed for all the receptor-ligand complexes. We also examined single mutant GABA(A)R (His102A) in complexes with the three drugs (flurazepam, eszopiclone and zolpidem) to elucidate receptor-ligand interactions. For each receptor-ligand complex (with flurazepam, eszopiclone and zolpidem), we calculated the average distance between the C(α) of the mutant residue His102A (α1) to the center of mass of the ligands. The results reveal that the distance between the C(α) of the mutant residue His102A (α1) to the center of flurazepam is larger than that between His102 (α1) to flurazepam in the WT type complex. Molecular mechanic-generalized Born surface area (MM-GBSA)-based binding free energy calculations were performed. The binding free energy was decomposed into ligand-residue pairs to create a ligand-residue interaction spectrum. The predicted binding free energies correlated well (R(2) = 0.87) with the experimental binding free energies. Overall, the major interaction comes from a few groups around His102 (α1), Phe77 (γ2) and Phe100 (α1). These groups of interaction consist of at least of 12 residues in total with a binding energy of more than 1 kcal mol(-1). The simulation study disclosed herein provides a meaningful insight into GABA(A)R-ligand interactions and helps to arrive at a binding mode hypothesis with implications for drug design.
[Mh] Termos MeSH primário: Simulação de Acoplamento Molecular
Ligação Proteica
Receptores de GABA-A/química
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Compostos Azabicíclicos/química
Sítios de Ligação
Zopiclona
Flurazepam/química
Seres Humanos
Ligantes
Modelos Moleculares
Piperazinas/química
Piridinas/química
Receptores de GABA-A/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Azabicyclo Compounds); 0 (Ligands); 0 (Piperazines); 0 (Pyridines); 0 (Receptors, GABA-A); 7K383OQI23 (zolpidem); IHP475989U (Flurazepam); UZX80K71OE (Eszopiclone)
[Em] Mês de entrada:1407
[Cu] Atualização por classe:171013
[Lr] Data última revisão:
171013
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:131119
[St] Status:MEDLINE
[do] DOI:10.1007/s00894-013-2049-8


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[PMID]:23841956
[Au] Autor:Teixeira J; Mota T; Fernandes JC
[Ad] Endereço:Centro Hospitalar Psiquiátrico de Lisboa, Lisboa, Portugal. jteixeira2008@gmail.com
[Ti] Título:Folie à deux: a case report.
[So] Source:Clin Schizophr Relat Psychoses;7(2):93-6, 2013.
[Is] ISSN:1935-1232
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Folie à deux is a relatively rare mental disorder first described in France in 1877 by Lasègue and Falret. However, folie à deux is still a matter of study and debate today as it remains a challenge for psychiatrists. The aim of our work is to report a clinical case of folie à deux, subtype A of Gralnick, between an inducer daughter and an induced mother who lived quite socially isolated and had a strong and close relationship. In the clinical case presented, folie à deux was easily diagnosed but its treatment proved to be a higher challenge. The main diagnosis of the inducer patient was also quite interesting. Many years after it was first described, folie à deux is still an interesting and challenging disorder to psychiatrists, especially concerning its pathophysiology and treatment.
[Mh] Termos MeSH primário: Transtorno Paranoide Compartilhado/diagnóstico
Transtorno Paranoide Compartilhado/tratamento farmacológico
[Mh] Termos MeSH secundário: Adulto
Antipsicóticos/uso terapêutico
Diagnóstico Diferencial
Feminino
Flurazepam/uso terapêutico
Seres Humanos
Meia-Idade
Relações Mãe-Filho
Cooperação do Paciente
Piperazinas/uso terapêutico
Transtorno Paranoide Compartilhado/psicologia
Isolamento Social/psicologia
Tiazóis/uso terapêutico
Recusa do Paciente ao Tratamento
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antipsychotic Agents); 0 (Piperazines); 0 (Thiazoles); 6UKA5VEJ6X (ziprasidone); IHP475989U (Flurazepam)
[Em] Mês de entrada:1309
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:130712
[St] Status:MEDLINE
[do] DOI:10.3371/CSRP.TEMU.120912


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[PMID]:23713025
[Au] Autor:Vogt S; Kempf J; Buttler J; Auwärter V; Weinmann W
[Ad] Endereço:Institute of Forensic Medicine, University Medical Center Freiburg, Albertstr. 9, D 79104, Freiburg, Germany.
[Ti] Título:Desalkylflurazepam found in patients' samples after high-dose midazolam treatment.
[So] Source:Drug Test Anal;5(9-10):745-7, 2013 Sep-Oct.
[Is] ISSN:1942-7611
[Cp] País de publicação:England
[La] Idioma:eng
[Mh] Termos MeSH primário: Flurazepam/análogos & derivados
Hipnóticos e Sedativos/sangue
Hipnóticos e Sedativos/urina
Midazolam/uso terapêutico
Entorpecentes/uso terapêutico
[Mh] Termos MeSH secundário: Feminino
Flurazepam/sangue
Flurazepam/urina
Parada Cardíaca/etiologia
Parada Cardíaca/terapia
Seres Humanos
Lactente
Midazolam/administração & dosagem
Entorpecentes/administração & dosagem
Ressuscitação
[Pt] Tipo de publicação:CASE REPORTS; LETTER
[Nm] Nome de substância:
0 (Hypnotics and Sedatives); 0 (Narcotics); BUJ3JOD7XF (didesethylflurazepam); IHP475989U (Flurazepam); R60L0SM5BC (Midazolam)
[Em] Mês de entrada:1405
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:130529
[St] Status:MEDLINE
[do] DOI:10.1002/dta.1484


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[PMID]:23624775
[Au] Autor:Hassanzadeh P; Hassanzadeh A
[Ad] Endereço:Nanomedicine and Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Evin, P.O. Box: 19835-187, Tehran, Iran, Pari_has@yahoo.com.
[Ti] Título:Implication of NGF and endocannabinoid signaling in the mechanism of action of sesamol: a multi-target natural compound with therapeutic potential.
[So] Source:Psychopharmacology (Berl);229(4):571-8, 2013 Oct.
[Is] ISSN:1432-2072
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Sesamol, a natural compound with anti-inflammatory, antioxidant and neuroprotective properties, has shown promising antidepressant-like effects. However, its molecular target(s) have not been well defined, which merits further investigation. OBJECTIVES: Based on the interaction between the neurotrophin and endocannabinoid (eCB) systems and their contribution to emotional reactivity and antidepressant action, we aimed to investigate the involvement of nerve growth factor (NGF) and eCB signalling in the mechanism of action of sesamol. METHODS: Following acute and 4-week intraperitoneal (i.p.) administration of sesamol (40, 80 and 100 mg/kg), the classical antidepressant amitriptyline (2.5, 5 and 10 mg/kg) or the benzodiazepine flurazepam (5, 10 and 20 mg/kg), brain regional levels of NGF and eCB contents were quantified in rats by Bio-Rad protein assay and isotope-dilution liquid chromatography/mass spectrometry, respectively. In the case of any significant change, the cannabinoid CB1 and CB2 receptor antagonists (AM251 and SR144528) were administered i.p. 30 min prior to the injection of sesamol, amitriptyline or flurazepam. RESULTS: Following the chronic treatment, sesamol, similar to amitriptyline, resulted in the sustained elevation of NGF and eCB contents in dose-dependent and brain region-specific fashion. Neither acute nor chronic treatment with flurazepam altered brain NGF or eCB contents. Pretreatment with 3 mg/kg AM251, but not SR144528, prevented the elevation of NGF protein levels. AM251 exerted no effect by itself. CONCLUSIONS: Sesamol, similar to amitriptyline, is able to affect brain NGF and eCB signalling under the regulatory drive of the CB1 receptors.
[Mh] Termos MeSH primário: Benzodioxóis/farmacologia
Endocanabinoides/metabolismo
Fator de Crescimento Neural/metabolismo
Fenóis/farmacologia
Receptor CB1 de Canabinoide/metabolismo
[Mh] Termos MeSH secundário: Amitriptilina/administração & dosagem
Amitriptilina/farmacologia
Animais
Antidepressivos Tricíclicos/administração & dosagem
Antidepressivos Tricíclicos/farmacologia
Antioxidantes/administração & dosagem
Antioxidantes/farmacologia
Benzodioxóis/administração & dosagem
Bornanos/farmacologia
Encéfalo/efeitos dos fármacos
Encéfalo/metabolismo
Relação Dose-Resposta a Droga
Flurazepam/administração & dosagem
Flurazepam/farmacologia
Injeções Intraperitoneais
Masculino
Terapia de Alvo Molecular
Fenóis/administração & dosagem
Piperidinas/farmacologia
Pirazóis/farmacologia
Ratos
Ratos Wistar
Receptor CB2 de Canabinoide/metabolismo
Transdução de Sinais/efeitos dos fármacos
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antidepressive Agents, Tricyclic); 0 (Antioxidants); 0 (Benzodioxoles); 0 (Bornanes); 0 (Endocannabinoids); 0 (Phenols); 0 (Piperidines); 0 (Pyrazoles); 0 (Receptor, Cannabinoid, CB1); 0 (Receptor, Cannabinoid, CB2); 0 (SR 144528); 1806D8D52K (Amitriptyline); 3I4FA44MAI (AM 251); 9061-61-4 (Nerve Growth Factor); 94IEA0NV89 (sesamol); IHP475989U (Flurazepam)
[Em] Mês de entrada:1405
[Cu] Atualização por classe:170920
[Lr] Data última revisão:
170920
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:130430
[St] Status:MEDLINE
[do] DOI:10.1007/s00213-013-3111-z


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[PMID]:22830051
[Au] Autor:Earl DE; Das P; Gunning WT; Tietz EI
[Ad] Endereço:Department of Physiology and Pharmacology, The University of Toledo College of Medicine, Health Science Campus, 3000 Arlington Avenue, Mailstop 1008, Toledo, OH 43614, USA.
[Ti] Título:Regulation of Ca²âº/calmodulin-dependent protein kinase II signaling within hippocampal glutamatergic postsynapses during flurazepam withdrawal.
[So] Source:Neural Plast;2012:405926, 2012.
[Is] ISSN:1687-5443
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cessation of one-week oral administration of the benzodiazepine flurazepam (FZP) to rats results in withdrawal anxiety after 1 day of withdrawal. FZP withdrawal is correlated with synaptic incorporation of homomeric GluA1-containing α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors (AMPARs) in the proximal stratum radiatum of CA1 neurons. After 2 days of withdrawal, Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) phosphorylates GluA1 subunits at Ser(831), increasing channel conductance. Secondary to AMPAR potentiation, GluN2B-containing N-methyl-D-aspartate receptors (NMDARs), known binding partners of CaMKII, are selectively removed from the postsynaptic density (PSD). While activation of synaptic CaMKII is known to involve translocation to the PSD, CaMKII bound to NMDARs may be removed from the PSD. To distinguish these possibilities, the current studies used postembedding immunogold electron microscopy to investigate alterations in CaMKII signaling at CA1 stratum radiatum synapses after 2 days of FZP withdrawal. These studies revealed decreased total, but not autophosphorylated (Thr(286)) CaMKIIα expression in CA1 PSDs. The removal of CaMKII-GluN2B complexes from the PSD during drug withdrawal may serve as a homeostatic mechanism to limit AMPAR-mediated CA1 neuron hyperexcitability and benzodiazepine withdrawal anxiety.
[Mh] Termos MeSH primário: Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/fisiologia
Flurazepam/efeitos adversos
Glutamatos/fisiologia
Hipocampo/fisiologia
Hipnóticos e Sedativos/efeitos adversos
Transdução de Sinais/fisiologia
Síndrome de Abstinência a Substâncias/fisiopatologia
Sinapses/fisiologia
[Mh] Termos MeSH secundário: Animais
Região CA1 Hipocampal/fisiologia
Espinhas Dendríticas/fisiologia
Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos
Homeostase/fisiologia
Imuno-Histoquímica
Masculino
Microscopia Eletrônica
Fosforilação
Terminações Pré-Sinápticas/fisiologia
Ratos
Ratos Sprague-Dawley
Receptores de N-Metil-D-Aspartato/fisiologia
Treonina/metabolismo
Inclusão do Tecido
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Glutamates); 0 (Hypnotics and Sedatives); 0 (Receptors, N-Methyl-D-Aspartate); 2ZD004190S (Threonine); EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2); IHP475989U (Flurazepam)
[Em] Mês de entrada:1211
[Cu] Atualização por classe:161019
[Lr] Data última revisão:
161019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:120726
[St] Status:MEDLINE
[do] DOI:10.1155/2012/405926


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[PMID]:22607251
[Au] Autor:Verster JC; Roth T
[Ad] Endereço:Utrecht Institute for Pharmaceutical Sciences, Division of Pharmacology, Utrecht University, Utrecht, The Netherlands. j.c.verster@uu.nl
[Ti] Título:Gender differences in highway driving performance after administration of sleep medication: a review of the literature.
[So] Source:Traffic Inj Prev;13(3):286-92, 2012.
[Is] ISSN:1538-957X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: It is generally assumed that there are minimal gender differences in the safety and efficacy of central nervous system drugs, as is evidenced by men and women receiving the same drug dosage. There is, however, evidence that drugs may have a differential effect on performance in men and women, given reported differences in pharmacokinetics as well as the presence or absence and severity of adverse effects. It is especially important to verify whether gender differences in performance exist in case of activities that have potentially dangerous outcomes such as driving a car. This review summarizes the current scientific evidence on gender differences in driving performance after treatment with hypnotic drugs. METHODS: A literature search was conducted to obtain all studies that conducted on-road driving tests to examine the effects hypnotic drugs on driving. Cross-references were checked and technical reports and raw data were obtained, if possible. RESULTS: Fourteen studies were evaluated. Many studies did not allow analyses of gender effects because only women were included. Others did not report data on gender analyses. Technical reports and additional data analyses revealed significant gender differences in driving performance the morning following bedtime administration of flurazepam (30 mg) and after middle-of-the-night administration of zolpidem (10 mg). No significant gender differences were found for ramelteon (8 mg), lormetazepam (1 and 2 mg), zaleplon (10 and 20 mg), and zopiclone (7.5 mg). CONCLUSIONS: Although the available data are limited, the results show that significant gender differences have been found for some drugs but not others. Therefore, in the future more research is needed to reveal potential gender differences and to determine what mediates them.
[Mh] Termos MeSH primário: Condução de Veículo/psicologia
Hipnóticos e Sedativos/farmacologia
Desempenho Psicomotor/efeitos dos fármacos
Fatores Sexuais
[Mh] Termos MeSH secundário: Acetamidas/administração & dosagem
Acetamidas/farmacologia
Compostos Azabicíclicos/administração & dosagem
Compostos Azabicíclicos/farmacologia
Planejamento Ambiental/estatística & dados numéricos
Feminino
Flurazepam/administração & dosagem
Flurazepam/farmacologia
Seres Humanos
Hipnóticos e Sedativos/administração & dosagem
Indenos/administração & dosagem
Indenos/farmacologia
Lorazepam/administração & dosagem
Lorazepam/análogos & derivados
Lorazepam/farmacologia
Masculino
Piperazinas/administração & dosagem
Piperazinas/farmacologia
Piridinas/administração & dosagem
Piridinas/farmacologia
Pirimidinas/administração & dosagem
Pirimidinas/farmacologia
Transtornos do Sono-Vigília/tratamento farmacológico
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Acetamides); 0 (Azabicyclo Compounds); 0 (Hypnotics and Sedatives); 0 (Indenes); 0 (Piperazines); 0 (Pyridines); 0 (Pyrimidines); 03A5ORL08Q (zopiclone); 7K383OQI23 (zolpidem); 901AS54I69 (ramelteon); GU56C842ZA (lormetazepam); IHP475989U (Flurazepam); O26FZP769L (Lorazepam); S62U433RMH (zaleplon)
[Em] Mês de entrada:1208
[Cu] Atualização por classe:161125
[Lr] Data última revisão:
161125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:120522
[St] Status:MEDLINE
[do] DOI:10.1080/15389588.2011.652751



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