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[PMID]:28822350
[Au] Autor:Liu J; Wang LN
[Ad] Endereço:Department of Neurology, Xuanwu Hospital, Capital Medical University, Changchun Street 45, Beijing, China, 100053.
[Ti] Título:Baclofen for alcohol withdrawal.
[So] Source:Cochrane Database Syst Rev;8:CD008502, 2017 08 20.
[Is] ISSN:1469-493X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Baclofen shows potential for rapidly reducing symptoms of severe alcohol withdrawal syndrome (AWS) in people with alcoholism. Treatment with baclofen is easy to manage and rarely produces euphoria or other pleasant effects, or craving for the drug. This is an updated version of the original Cochrane Review published in 2015, Issue 4. OBJECTIVES: To assess the efficacy and safety of baclofen for people with AWS. SEARCH METHODS: We updated our searches of the following databases to March 2017: the Cochrane Drugs and Alcohol Group Specialised Register, CENTRAL, PubMed, Embase, and CINAHL. We also searched registers of ongoing trials. We handsearched the references quoted in the identified trials, and sought information from researchers, pharmaceutical companies, and relevant trial authors about unpublished or uncompleted trials. We placed no restrictions on language. SELECTION CRITERIA: We included all randomised controlled clinical trials (RCTs) evaluating baclofen versus placebo or any other treatment for people with AWS. We excluded uncontrolled, non-randomised, or quasi-randomised trials. We included both parallel group and cross-over studies. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included three RCTs with 141 randomised participants. We did not perform meta-analyses due to the different control interventions. For the comparison of baclofen and placebo (1 study, 31 participants), there was no significant difference in Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar) scores (very low quality evidence). For the comparison of baclofen and diazepam (1 study, 37 participants), there was no significant difference in CIWA-Ar scores (very low quality evidence), adverse events (risk difference (RD) 0.00, 95% confidence interval (CI) -0.10 to 0.10; very low quality evidence), dropouts (RD 0.00, 95% CI -0.10 to 0.10; very low quality evidence), and dropouts due to adverse events (RD 0.00, 95% CI -0.10 to 0.10; very low quality evidence). For the comparison of baclofen and chlordiazepoxide (1 study, 60 participants), there was no significant difference in CIWA-Ar scores (mean difference (MD) 1.00, 95% CI 0.70 to 1.30; very low quality evidence), global improvement (MD 0.10, 95% CI -0.03 to 0.23; very low quality evidence), adverse events (RD 2.50, 95% CI 0.88 to 7.10; very low quality of evidence), dropouts (RD 0.00, 95% CI -0.06 to 0.06; very low quality evidence), and dropouts due to adverse events (RD 0.00, 95% CI -0.06 to 0.06; very low quality evidence). AUTHORS' CONCLUSIONS: No conclusions can be drawn about the efficacy and safety of baclofen for the management of alcohol withdrawal because we found insufficient and very low quality evidence.
[Mh] Termos MeSH primário: Transtornos Induzidos por Álcool/tratamento farmacológico
Baclofeno/uso terapêutico
Clordiazepóxido/uso terapêutico
Diazepam/uso terapêutico
Agonistas GABAérgicos/uso terapêutico
Síndrome de Abstinência a Substâncias/tratamento farmacológico
[Mh] Termos MeSH secundário: Baclofeno/efeitos adversos
Clordiazepóxido/efeitos adversos
Diazepam/efeitos adversos
Etanol/efeitos adversos
Agonistas GABAérgicos/efeitos adversos
Seres Humanos
Ensaios Clínicos Controlados Aleatórios como Assunto
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (GABA Agonists); 3K9958V90M (Ethanol); 6RZ6XEZ3CR (Chlordiazepoxide); H789N3FKE8 (Baclofen); Q3JTX2Q7TU (Diazepam)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170919
[Lr] Data última revisão:
170919
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170820
[St] Status:MEDLINE
[do] DOI:10.1002/14651858.CD008502.pub5


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[PMID]:27328370
[Au] Autor:Costa AA; Tinós R
[Ad] Endereço:Department of Physics, FFCLRP, University of São Paulo, 14040-901 Ribeirão Preto, SP, Brazil. Electronic address: ad.andrade.costa@gmail.com.
[Ti] Título:Investigation of rat exploratory behavior via evolving artificial neural networks.
[So] Source:J Neurosci Methods;270:102-110, 2016 09 01.
[Is] ISSN:1872-678X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Neuroevolution comprises the use of evolutionary computation to define the architecture and/or to train artificial neural networks (ANNs). This strategy has been employed to investigate the behavior of rats in the elevated plus-maze, which is a widely used tool for studying anxiety in mice and rats. NEW METHOD: Here we propose a neuroevolutionary model, in which both the weights and the architecture of artificial neural networks (our virtual rats) are evolved by a genetic algorithm. COMPARISON WITH EXISTING METHOD(S): This model is an improvement of a previous model that involves the evolution of just the weights of the ANN by the genetic algorithm. In order to compare both models, we analyzed traditional measures of anxiety behavior, like the time spent and the number of entries in both open and closed arms of the maze. RESULTS: When compared to real rat data, our findings suggest that the results from the model introduced here are statistically better than those from other models in the literature. CONCLUSIONS: In this way, the neuroevolution of architecture is clearly important for the development of the virtual rats. Moreover, this technique allowed the comprehension of the importance of different sensory units and different number of hidden neurons (performing as memory) in the ANNs (virtual rats).
[Mh] Termos MeSH primário: Ansiedade
Comportamento Exploratório
Redes Neurais (Computação)
[Mh] Termos MeSH secundário: Animais
Ansiedade/induzido quimicamente
Ansiedade/tratamento farmacológico
Ansiedade/fisiopatologia
Clordiazepóxido/farmacologia
Comportamento Exploratório/efeitos dos fármacos
Psicotrópicos
Ratos
Semicarbazidas/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Psychotropic Drugs); 0 (Semicarbazides); 37QUC23K2X (carbamylhydrazine); 6RZ6XEZ3CR (Chlordiazepoxide)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171127
[Lr] Data última revisão:
171127
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160622
[St] Status:MEDLINE


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[PMID]:27180106
[Au] Autor:Tyree SM; Munn RG; McNaughton N
[Ad] Endereço:Department of Psychology, University of Otago, Dunedin, New Zealand. Electronic address: suszie.tyree@gmail.com.
[Ti] Título:Anxiolytic-like effects of leptin on fixed interval responding.
[So] Source:Pharmacol Biochem Behav;148:15-20, 2016 Sep.
[Is] ISSN:1873-5177
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Leptin has been shown to affect energy homeostasis, learning and memory, and some models of anxiolytic action. However, leptin has produced inconsistent results in previous non-operant behavioural tests of anxiety. Here, we test the anxiolytic potential of leptin in an operant paradigm that has produced positive results across all classes of anxiolytic so far tested. Rats were tested in the Fixed Interval 60 Seconds (FI60) task following administration of 0/0.5/1.0mg/kg (i.p.) leptin or an active anxiolytic control of 5mg/kg (i.p.) chlordiazepoxide (CDP). By the end of the 14days of testing in the FI60 task, 0.5mg/kg leptin released suppressed responding in a manner similar to CDP, and 1.0mg/kg leptin produced a relative depression in responding, a similar outcome pattern to previously tested 5HT-agonist anxiolytics. This suggests that leptin behaves similarly to established serotonergic anxiolytics such as buspirone and fluoxetine; with the delay in development of effect during testing, and the inverted-U dose-response curve explaining the inconsistent behaviour of leptin in behavioural tests of anxiety, as this type of pattern is common to serotonergic anxiolytics.
[Mh] Termos MeSH primário: Ansiolíticos/farmacologia
Leptina/farmacologia
[Mh] Termos MeSH secundário: Animais
Clordiazepóxido/farmacologia
Relação Dose-Resposta a Droga
Masculino
Ratos
Ratos Sprague-Dawley
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Anxiety Agents); 0 (Leptin); 6RZ6XEZ3CR (Chlordiazepoxide)
[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:160516
[St] Status:MEDLINE


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[PMID]:27105601
[Au] Autor:Girish K; Vikram Reddy K; Pandit LV; Pundarikaksha HP; Vijendra R; Vasundara K; Manjunatha R; Nagraj M; Shruthi R
[Ad] Endereço:Department of Pharmacology, KIMS Hospital and Research Center, Bengaluru, Karnataka, India.
[Ti] Título:A randomized, open-label, standard controlled, parallel group study of efficacy and safety of baclofen, and chlordiazepoxide in uncomplicated alcohol withdrawal syndrome.
[So] Source:Biomed J;39(1):72-80, 2016 Feb.
[Is] ISSN:2320-2890
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Alcohol withdrawal syndrome (AWS) is a distressing condition, generally controlled by benzodiazepines (BZD's). Baclofen, a gamma-aminobutyric acid-B (GABAB) agonist, has also shown promising results in controlling AWS. As there are few studies comparing the efficacy and tolerability of chlordiazepoxide with baclofen, the present study was taken up. The objective of this study was to compare efficacy and tolerability of baclofen with chlordiazepoxide in uncomplicated AWS. METHODS: Sixty subjects with uncomplicated AWS were randomized into two groups of 30 each, to receive baclofen (30 mg) or chlordiazepoxide (75 mg) in decremented fixed dose regime for 9 days. Clinical efficacy was assessed by Clinical Institute Withdrawal Assessment for Alcohol-Revised Scale (CIWA-Ar) and tolerability by the nature and severity of adverse events. Lorazepam was used as rescue medication. Secondary efficacy parameters were Clinical Global Impression scores, symptom-free days, and subject satisfaction as assessed by visual analog scale. This study was registered with Clinical Trial Registry-India (CTRI/2013/04/003588), also subsequently registered with WHO's ICTRP clinical trial portal. RESULTS: Both baclofen and chlordiazepoxide showed a consistent reduction in the total CIWA-Ar scores. However, chlordiazepoxide showed a faster and a more effective control of anxiety and agitation requiring lesser lorazepam supplementation, and also showed a better subject satisfaction compared to baclofen. Both the drugs showed good tolerability with mild self-limiting adverse events. CONCLUSION: The present study demonstrates that baclofen is not as good as chlordiazepoxide in the treatment of uncomplicated AWS. However, baclofen might be considered as an alternative.
[Mh] Termos MeSH primário: Baclofeno/uso terapêutico
Clordiazepóxido/uso terapêutico
Síndrome de Abstinência a Substâncias/tratamento farmacológico
[Mh] Termos MeSH secundário: Adulto
Consumo de Bebidas Alcoólicas
Baclofeno/administração & dosagem
Baclofeno/efeitos adversos
Clordiazepóxido/efeitos adversos
Diazepam/uso terapêutico
Seres Humanos
Lorazepam/uso terapêutico
Masculino
Meia-Idade
Síndrome de Abstinência a Substâncias/diagnóstico
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
6RZ6XEZ3CR (Chlordiazepoxide); H789N3FKE8 (Baclofen); O26FZP769L (Lorazepam); Q3JTX2Q7TU (Diazepam)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160424
[St] Status:MEDLINE


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[PMID]:26922279
[Au] Autor:Askgaard G; Hallas J; Fink-Jensen A; Molander AC; Madsen KG; Pottegård A
[Ad] Endereço:Department of Hepatology, Copenhagen University Hospital, Rigshospitalet, Denmark. Electronic address: gask@dadlnet.dk.
[Ti] Título:Phenobarbital compared to benzodiazepines in alcohol withdrawal treatment: A register-based cohort study of subsequent benzodiazepine use, alcohol recidivism and mortality.
[So] Source:Drug Alcohol Depend;161:258-64, 2016 Apr 01.
[Is] ISSN:1879-0046
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Long-acting benzodiazepines such as chlordiazepoxide are recommended as first-line treatment for alcohol withdrawal. These drugs are known for their abuse liability and might increase alcohol consumption among problem drinkers. Phenobarbital could be an alternative treatment option, possibly with the drawback of a more pronounced acute toxicity. We evaluated if phenobarbital compared to chlordiazepoxide decreased the risk of subsequent use of benzodiazepines, alcohol recidivism and mortality. METHODS: The study was a register-based cohort study of patients admitted for alcohol withdrawal 1998-2013 and treated with either phenobarbital or chlordiazepoxide. Patients were followed for one year. We calculated hazard ratios (HR) for benzodiazepine use, alcohol recidivism and mortality associated with alcohol withdrawal treatment, while adjusting for confounders. RESULTS: A total of 1063 patients treated with chlordiazepoxide and 1365 patients treated with phenobarbital were included. After one year, the outcome rates per 100 person-years in the phenobarbital versus the chlordiazepoxide cohort were 9.20 vs. 5.13 for use of benzodiazepine, 37.9 vs. 37.9 for alcohol recidivism and 29 vs. 59 for mortality. Comparing phenobarbital to chlordiazepoxide treated, the HR of subsequent use of benzodiazepines was 1.56 (95%CI 1.05-2.30). Similarly, the HR for alcohol recidivism was 0.99 (95%CI 0.84-1.16). Lastly, the HR for 30-days and 1 year mortality was 0.25 (95%CI 0.08-0.78) and 0.51 (95%CI 0.31-0.86). CONCLUSION: There was no decreased risk of subsequent benzodiazepine use or alcohol recidivism in patients treated with phenobarbital compared to chlordiazepoxide. Phenobarbital treatment was associated with decreased mortality, which might be confounded by somatic comorbidity among patients receiving chlordiazepoxide.
[Mh] Termos MeSH primário: Alcoolismo/tratamento farmacológico
Benzodiazepinas/uso terapêutico
Clordiazepóxido/uso terapêutico
Etanol/efeitos adversos
Moduladores GABAérgicos/uso terapêutico
Fenobarbital/uso terapêutico
Síndrome de Abstinência a Substâncias/tratamento farmacológico
[Mh] Termos MeSH secundário: Adulto
Estudos de Coortes
Feminino
Hospitalização
Seres Humanos
Tempo de Internação
Masculino
Meia-Idade
Sistema de Registros
Resultado do Tratamento
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (GABA Modulators); 12794-10-4 (Benzodiazepines); 3K9958V90M (Ethanol); 6RZ6XEZ3CR (Chlordiazepoxide); YQE403BP4D (Phenobarbital)
[Em] Mês de entrada:1611
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160229
[St] Status:MEDLINE


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[PMID]:26655106
[Au] Autor:Pebdani AA; Khodadoust S; Talebianpoor MS; Zargar HR; Zarezade V
[Ad] Endereço:Behbahan Faculty of Medical Sciences, Behbahan, Iran.
[Ti] Título:Preconcentration and determination of chlordiazepoxide and diazepam drugs using dispersive nanomaterial-ultrasound assisted microextraction method followed by high performance liquid chromatography.
[So] Source:J Chromatogr B Analyt Technol Biomed Life Sci;1008:146-155, 2016 Jan 01.
[Is] ISSN:1873-376X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Benzodiazepines (BDs) are used widely in clinical practice, due to their multiple pharmacological functions. In this study a dispersive nanomaterial-ultrasound assisted- microextraction (DNUM) method followed by high performance liquid chromatography (HPLC) was used for the preconcentration and determination of chlordiazepoxide and diazepam drugs from urine and plasma samples. Various parameters such as amount of adsorbent (mg: ZnS-AC), pH and ionic strength of sample solution, vortex and ultrasonic time (min), and desorption volume (mL) were investigated by fractional factorial design (FFD) and central composite design (CCD). Regression models and desirability functions (DF) were applied to find the best experimental conditions for providing the maximum extraction recovery (ER). Under the optimal conditions a linear calibration curve were obtained in the range of 0.005-10µgmL(-1) and 0.006-10µgmL(-1) for chlordiazepoxide and diazepam, respectively. To demonstrate the analytical performance, figures of merits of the proposed method in urine and plasma spiked with chlordiazepoxide and diazepam were investigated. The limits of detection of chlordiazepoxide and diazepam in urine and plasma were ranged from 0.0012 to 0.0015µgmL(-1), respectively.
[Mh] Termos MeSH primário: Clordiazepóxido/análise
Cromatografia Líquida de Alta Pressão/métodos
Diazepam/análise
Nanoestruturas
[Mh] Termos MeSH secundário: Clordiazepóxido/sangue
Clordiazepóxido/urina
Diazepam/sangue
Diazepam/urina
Seres Humanos
Microscopia Eletrônica de Transmissão
Difração de Raios X
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; VALIDATION STUDIES
[Nm] Nome de substância:
6RZ6XEZ3CR (Chlordiazepoxide); Q3JTX2Q7TU (Diazepam)
[Em] Mês de entrada:1608
[Cu] Atualização por classe:170816
[Lr] Data última revisão:
170816
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151215
[St] Status:MEDLINE


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[PMID]:26562180
[Au] Autor:Lotfy HM; Fayez YM; Michael AM; Nessim CK
[Ad] Endereço:Pharmaceutical Chemistry Department, Faculty of Pharmaceutical Sciences & Pharmaceutical Industries, Future University, 12311 Cairo, Egypt.
[Ti] Título:Simultaneous determination of mebeverine hydrochloride and chlordiazepoxide in their binary mixture using novel univariate spectrophotometric methods via different manipulation pathways.
[So] Source:Spectrochim Acta A Mol Biomol Spectrosc;155:11-20, 2016 Feb 15.
[Is] ISSN:1873-3557
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Smart, sensitive, simple and accurate spectrophotometric methods were developed and validated for the quantitative determination of a binary mixture of mebeverine hydrochloride (MVH) and chlordiazepoxide (CDZ) without prior separation steps via different manipulating pathways. These pathways were applied either on zero order absorption spectra namely, absorbance subtraction (AS) or based on the recovered zero order absorption spectra via a decoding technique namely, derivative transformation (DT) or via ratio spectra namely, ratio subtraction (RS) coupled with extended ratio subtraction (EXRS), spectrum subtraction (SS), constant multiplication (CM) and constant value (CV) methods. The manipulation steps applied on the ratio spectra are namely, ratio difference (RD) and amplitude modulation (AM) methods or applying a derivative to these ratio spectra namely, derivative ratio (DD(1)) or second derivative (D(2)). Finally, the pathway based on the ratio spectra of derivative spectra is namely, derivative subtraction (DS). The specificity of the developed methods was investigated by analyzing the laboratory mixtures and was successfully applied for their combined dosage form. The proposed methods were validated according to ICH guidelines. These methods exhibited linearity in the range of 2-28µg/mL for mebeverine hydrochloride and 1-12µg/mL for chlordiazepoxide. The obtained results were statistically compared with those of the official methods using Student t-test, F-test, and one way ANOVA, showing no significant difference with respect to accuracy and precision.
[Mh] Termos MeSH primário: Anticonvulsivantes/análise
Clordiazepóxido/análise
Hipnóticos e Sedativos/análise
Fenetilaminas/análise
Espectrofotometria/métodos
[Mh] Termos MeSH secundário: Análise de Variância
Combinação de Medicamentos
Limite de Detecção
[Pt] Tipo de publicação:JOURNAL ARTICLE; VALIDATION STUDIES
[Nm] Nome de substância:
0 (Anticonvulsants); 0 (Drug Combinations); 0 (Hypnotics and Sedatives); 0 (Phenethylamines); 6RZ6XEZ3CR (Chlordiazepoxide); 7F80CC3NNV (mebeverine)
[Em] Mês de entrada:1610
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151113
[St] Status:MEDLINE


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[PMID]:26139659
[Au] Autor:Fossat P; Bacqué-Cazenave J; De Deurwaerdère P; Cattaert D; Delbecque JP
[Ad] Endereço:Université de Bordeaux, 33400 Talence, France Centre National de la Recherche Scientifique (CNRS), UMR 5287, Institut des Neurosciences Cognitives et Intégratives d'Aquitaine, Avenue des Facultés, 33405 Talence Cedex, France.
[Ti] Título:Serotonin, but not dopamine, controls the stress response and anxiety-like behavior in the crayfish Procambarus clarkii.
[So] Source:J Exp Biol;218(Pt 17):2745-52, 2015 Sep.
[Is] ISSN:1477-9145
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:In the animal kingdom, biogenic amines are widespread modulators of the nervous system that frequently interact to control mood. Our previous investigations in crayfish (Procambarus clarkii) have established that stress induces changes in brain serotonin (5-HT) concentrations that are responsible for the appearance of anxiety-like behavior (ALB). Here, we further analyze the roles of 5-HT and another biogenic amine, dopamine (DA), on the crayfish response to stress. We show that the intensity of crayfish ALB depends on the intensity of stressful stimulation and is associated with increased concentrations of 5-HT in the brain. These 5-HT levels were significantly correlated, before, as well as after stress, with those of DA, which were approximately 3- to 5-times less abundant. However, whereas the degree of ALB was clearly correlated with brain 5-HT concentrations, it was not significantly correlated with DA. Moreover, in contrast to injections of 5-HT, DA injections were not able to elicit a stress response or ALB. In addition, 5-HT and DA levels were not modified by treatment with the anxiolytic chlordiazepoxide, confirming that suppression of ALB by this GABA-A receptor ligand acts downstream and is independent of changes in crayfish bioamine levels. Our study also provides evidence that the anxiogenic effect of 5-HT injections can be prevented by a preliminary injection of 5-HT antagonists. Altogether, our results emphasize that the rises in brain concentrations of 5-HT, but not DA, play a role in controlling the induction and the intensity of crayfish ALB.
[Mh] Termos MeSH primário: Astacoidea/efeitos dos fármacos
Astacoidea/fisiologia
Dopamina/farmacologia
Serotonina/farmacologia
[Mh] Termos MeSH secundário: Animais
Comportamento Animal/efeitos dos fármacos
Química Encefálica
Clordiazepóxido/farmacologia
Dopamina/metabolismo
Estimulação Elétrica
Masculino
Receptores de GABA-A
Serotonina/metabolismo
Antagonistas da Serotonina/farmacologia
Estresse Fisiológico
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Receptors, GABA-A); 0 (Serotonin Antagonists); 333DO1RDJY (Serotonin); 6RZ6XEZ3CR (Chlordiazepoxide); VTD58H1Z2X (Dopamine)
[Em] Mês de entrada:1607
[Cu] Atualização por classe:150903
[Lr] Data última revisão:
150903
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150704
[St] Status:MEDLINE
[do] DOI:10.1242/jeb.120550


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[PMID]:26133736
[Au] Autor:Varga J; Fodor A; Klausz B; Zelena D
[Ad] Endereço:Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
[Ti] Título:Anxiogenic role of vasopressin during the early postnatal period: maternal separation-induced ultrasound vocalization in vasopressin-deficient Brattleboro rats.
[So] Source:Amino Acids;47(11):2409-18, 2015 Nov.
[Is] ISSN:1438-2199
[Cp] País de publicação:Austria
[La] Idioma:eng
[Ab] Resumo:Both animal and human studies suggest that in adulthood, plasma vasopressin level correlates well with anxiety. Little is known about the mood regulation during the perinatal period. Here, we aim to investigate the influence of vasopressin on anxiety during the early postnatal age. As a sign of distress, rat pups emit ultrasonic vocalizations (USVs) when they are separated from their mother. This USV was detected in 7- to 8-day-old vasopressin-deficient Brattleboro pups, and they were compared to their heterozygote littermates and wild-type pups. The results were confirmed by V1b antagonist treatment (SSR149415 10 mg/kg ip 30 min before test) in wild-types. Chlordiazepoxide (3 mg/kg ip 30 min before test)-an anxiolytic-was used to test the interaction with the GABAergic system. At the end of the test, stress-hormone levels were measured by radioimmunoassay. Vasopressin-deficient pups vocalized substantially less than non-deficient counterparts. Treatment with V1b antagonist resulted in similar effect. Chlordiazepoxide reduced the frequency and duration of the vocalization only in wild-types. Reduced vocalization was accompanied by smaller adrenocorticotropin levels but the level of corticosterone was variable. Our results indicate that the anxiolytic effect of vasopressin deficiency (both genetic and pharmacological) exists already during the early postnatal age. Vasopressin interacts with the GABAergic system. As mood regulation does not go parallel with glucocorticoid levels, we suggest that vasopressin might have a direct effect on special brain areas.
[Mh] Termos MeSH primário: Afeto/efeitos dos fármacos
Ansiedade/metabolismo
Período Pós-Parto/metabolismo
Vasopressinas
Vocalização Animal/efeitos dos fármacos
[Mh] Termos MeSH secundário: Hormônio Adrenocorticotrópico/metabolismo
Animais
Clordiazepóxido/farmacologia
Corticosterona/metabolismo
Feminino
Seres Humanos
Ratos
Ratos Brattleboro
Vasopressinas/metabolismo
Vasopressinas/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
11000-17-2 (Vasopressins); 6RZ6XEZ3CR (Chlordiazepoxide); 9002-60-2 (Adrenocorticotropic Hormone); W980KJ009P (Corticosterone)
[Em] Mês de entrada:1608
[Cu] Atualização por classe:151027
[Lr] Data última revisão:
151027
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150703
[St] Status:MEDLINE
[do] DOI:10.1007/s00726-015-2034-x


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[PMID]:25823809
[Au] Autor:Kato T; Takata M; Kitaichi M; Kassai M; Inoue M; Ishikawa C; Hirose W; Yoshida K; Shimizu I
[Ad] Endereço:Drug Development Research Laboratories, Sumitomo Dainippon Pharma Co., Ltd., 33-94 Enoki-cho, Suita, Osaka 564-0053, Japan. Electronic address: taro-kato@ds-pharma.co.jp.
[Ti] Título:DSR-98776, a novel selective mGlu5 receptor negative allosteric modulator with potent antidepressant and antimanic activity.
[So] Source:Eur J Pharmacol;757:11-20, 2015 Jun 15.
[Is] ISSN:1879-0712
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Modulation of monoaminergic systems has been the main stream of treatment for patients with mood disorders. However, recent evidence suggests that the glutamatergic system plays an important role in the pathophysiology of these disorders. This study pharmacologically characterized a structurally novel metabotropic glutamate 5 (mGlu5) receptor negative allosteric modulator, DSR-98776, and evaluated its effect on rodent models of depression and mania. First, DSR-98776 in vitro profile was assessed using intracellular calcium and radioligand binding assays. This compound showed dose-dependent inhibitory activity for mGlu5 receptors by binding to the same allosteric site as 2-methyl-6-(phenylethynyl)-pyridine (MPEP), a known mGlu5 inhibitor. The in vivo therapeutic benefits of DSR-98776 were evaluated in common rodent models of depression and mania. In the rat forced swimming test, DSR-98776 (1-3mg/kg) significantly reduced rats immobility time after treatment for 7 consecutive days, while paroxetine (3 and 10mg/kg) required administration for 2 consecutive weeks to reduce rats immobility time. In the mouse forced swimming test, acute administration of DSR-98776 (10-30 mg/kg) significantly reduced immobility time. This effect was not influenced by 4-chloro-DL-phenylalanine methyl ester hydrochloride-induced 5-HT depletion. Finally, DSR-98776 (30 mg/kg) significantly decreased methamphetamine/chlordiazepoxide-induced hyperactivity in mice, which reflects this compound antimanic-like effect. These results indicate that DSR-98776 acts as an orally potent antidepressant and antimanic in rodent models and can be a promising therapeutic option for the treatment of a broad range of mood disorders with depressive and manic states.
[Mh] Termos MeSH primário: Antidepressivos/farmacologia
Antimaníacos/farmacologia
Di-Hidropiridinas/farmacologia
Oxazóis/farmacologia
Piridinas/farmacologia
Receptor de Glutamato Metabotrópico 5/metabolismo
[Mh] Termos MeSH secundário: Regulação Alostérica/efeitos dos fármacos
Animais
Antidepressivos/uso terapêutico
Antimaníacos/uso terapêutico
Cálcio/metabolismo
Clordiazepóxido/farmacologia
Di-Hidropiridinas/uso terapêutico
Células HEK293
Seres Humanos
Espaço Intracelular/efeitos dos fármacos
Espaço Intracelular/metabolismo
Masculino
Metanfetamina/farmacologia
Camundongos
Oxazóis/uso terapêutico
Agitação Psicomotora/tratamento farmacológico
Agitação Psicomotora/etiologia
Piridinas/metabolismo
Piridinas/uso terapêutico
Ratos
Serotonina/deficiência
Natação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (3-methoxy-5-pyridin-2-ylethynylpyridine); 0 (Antidepressive Agents); 0 (Antimanic Agents); 0 (DSR-98776); 0 (Dihydropyridines); 0 (Oxazoles); 0 (Pyridines); 0 (Receptor, Metabotropic Glutamate 5); 333DO1RDJY (Serotonin); 44RAL3456C (Methamphetamine); 6RZ6XEZ3CR (Chlordiazepoxide); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1602
[Cu] Atualização por classe:150429
[Lr] Data última revisão:
150429
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150401
[St] Status:MEDLINE



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