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[PMID]:26752621
[Au] Autor:Agorastos A; Demiralay C; Stiedl O; Muhtz C; Wiedemann K; Kellner M
[Ad] Endereço:Departments of aPsychiatry and Psychotherapy bPsychosomatic Medicine and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany Departments of cFunctional Genomics dMolecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University Amsterdam, Amsterdam, The Netherlands.
[Ti] Título:Metabotropic glutamate2/3 receptor agonism facilitates autonomic recovery after pharmacological panic challenge in healthy humans.
[So] Source:Int Clin Psychopharmacol;31(3):176-8, 2016 May.
[Is] ISSN:1473-5857
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Group II metabotropic glutamate receptors (mGluR2/3) are suggested to modulate anxiety, arousal, and stress including autonomic control. However, no study has investigated mGluR2/3-related effects on baseline autonomic activity and reactivity to emotional challenge in humans as yet. Using a double-blind, randomized placebo-controlled, cross-over study design, we investigated the influence of a 1-week treatment with the mGluR2/3 agonist LY544344, prodrug of LY354740, on autonomic reactivity to a cholecystokinin tetrapeptide (CCK-4) panic challenge in eight healthy young men. The main outcome measures were time and frequency domain heart rate variability parameters during baseline, CCK-4 challenge, and recovery. There was no evidence for LY544344-mediated effects on baseline and CCK-4 challenge vagal activity, but a significantly lower recovery low frequency (%) and low frequency/high frequency ratio in the LY544344 group, suggesting enhanced autonomic recovery. This pilot study provides first human data indicating that mGluR2/3 agonism is involved in autonomic responsiveness, suggesting an important role of mGluR2/3 in central autonomic regulation.
[Mh] Termos MeSH primário: Alanina/análogos & derivados
Compostos Bicíclicos com Pontes/farmacologia
Frequência Cardíaca/efeitos dos fármacos
Pânico/efeitos dos fármacos
Receptores de Glutamato Metabotrópico/agonistas
Tetragastrina/farmacologia
[Mh] Termos MeSH secundário: Adulto
Alanina/farmacologia
Estudos Cross-Over
Método Duplo-Cego
Voluntários Saudáveis
Seres Humanos
Masculino
Projetos Piloto
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (2-((2'-amino)propionyl)aminobicyclo(3.1.0)hexane-2,6-dicarboxylic acid); 0 (Bridged Bicyclo Compounds); 0 (Receptors, Metabotropic Glutamate); 0 (metabotropic glutamate receptor 2); 0 (metabotropic glutamate receptor 3); 0OL293AV80 (Tetragastrin); OF5P57N2ZX (Alanine)
[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:160112
[St] Status:MEDLINE
[do] DOI:10.1097/YIC.0000000000000117


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[PMID]:26235955
[Au] Autor:Ruland T; Domschke K; Schütte V; Zavorotnyy M; Kugel H; Notzon S; Vennewald N; Ohrmann P; Arolt V; Pfleiderer B; Zwanzger P
[Ad] Endereço:Mood and Anxiety Disorders Research Unit, Department of Psychiatry and Psychotherapy, University of Muenster, Germany.
[Ti] Título:Neuropeptide S receptor gene variation modulates anterior cingulate cortex Glx levels during CCK-4 induced panic.
[So] Source:Eur Neuropsychopharmacol;25(10):1677-82, 2015 Oct.
[Is] ISSN:1873-7862
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:An excitatory-inhibitory neurotransmitter dysbalance has been suggested in pathogenesis of panic disorder. The neuropeptide S (NPS) system has been implicated in modulating GABA and glutamate neurotransmission in animal models and to genetically drive altered fear circuit function and an increased risk of panic disorder in humans. Probing a multi-level imaging genetic risk model of panic, in the present magnetic resonance spectroscopy (MRS) study brain glutamate+glutamine (Glx) levels in the bilateral anterior cingulate cortex (ACC) during a pharmacological cholecystokinin tetrapeptide (CCK-4) panic challenge were assessed depending on the functional neuropeptide S receptor gene (NPSR1) rs324981 A/T variant in a final sample of 35 healthy male subjects. The subjective panic response (Panic Symptom Scale; PSS) as well as cortisol and ACTH levels were ascertained throughout the experiment. CCK-4 injection was followed by a strong panic response. A significant time×genotype interaction was detected (p=.008), with significantly lower ACC Glx/Cr levels in T allele carriers as compared to AA homozygotes 5min after injection (p=.003). CCK-4 induced significant HPA axis stimulation, but no effect of genotype was discerned. The present pilot data suggests NPSR1 gene variation to modulate Glx levels in the ACC during acute states of stress and anxiety, with blunted, i.e. possibly maladaptive ACC glutamatergic reactivity in T risk allele carriers. Our results underline the notion of a genetically driven rapid and dynamic response mechanism in the neural regulation of human anxiety and further strengthen the emerging role of the NPS system in anxiety.
[Mh] Termos MeSH primário: Ácido Glutâmico/metabolismo
Glutamina/metabolismo
Giro do Cíngulo/metabolismo
Pânico/fisiologia
Receptores Acoplados a Proteínas-G/genética
[Mh] Termos MeSH secundário: Hormônio Adrenocorticotrópico/sangue
Adulto
Análise Química do Sangue
Creatina/metabolismo
Ensaio de Imunoadsorção Enzimática
Genótipo
Técnicas de Genotipagem
Seres Humanos
Hidrocortisona/sangue
Masculino
Projetos Piloto
Espectroscopia de Prótons por Ressonância Magnética
Escalas de Graduação Psiquiátrica
Tetragastrina
Fatores de Tempo
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (NPSR1 protein, human); 0 (Receptors, G-Protein-Coupled); 0OL293AV80 (Tetragastrin); 0RH81L854J (Glutamine); 3KX376GY7L (Glutamic Acid); 9002-60-2 (Adrenocorticotropic Hormone); MU72812GK0 (Creatine); WI4X0X7BPJ (Hydrocortisone)
[Em] Mês de entrada:1607
[Cu] Atualização por classe:151010
[Lr] Data última revisão:
151010
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150804
[St] Status:MEDLINE


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[PMID]:25522396
[Au] Autor:Agorastos A; Kellner M; Stiedl O; Muhtz C; Wiedemann K; Demiralay C
[Ad] Endereço:Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (Drs Agorastos, Kellner, Muhtz, Wiedemann, and Demiralay); Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus, VU University, Amsterdam, Neth
[Ti] Título:Blunted autonomic reactivity to pharmacological panic challenge under long-term escitalopram treatment in healthy men.
[So] Source:Int J Neuropsychopharmacol;18(5), 2014 Dec 11.
[Is] ISSN:1469-5111
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Central serotonergic pathways influence brain areas involved in vagal cardiovascular regulation and, thereby, influence sympathetic efferent activity. Selective serotonin reuptake inhibitors (SSRIs) affect multiple serotonergic pathways, including central autonomic pathways. However, only a few studies have assessed SSRI-mediated effects on autonomic reactivity in healthy individuals using heart rate variability (HRV). METHODS: The present study assessed the influence of long-term treatment with escitalopram (ESC) on autonomic reactivity to an intravenous application of 50 µg cholecystokinin tetrapeptide (CCK-4) in 30 healthy young men using a double-blind, placebo (PLA)-controlled, randomized, within-subject cross-over design. Main outcome measures were time- and frequency-domain HRV parameters, assessed at both baseline and immediately after CCK-4 application. RESULTS: Results showed substantial effects for the treatment × CCK-4 challenge interaction with respect to heart rate (p < 0.001; pη(2) = 0.499), SDNN (p < 0.001; pη(2) = 576), RMSSD (p = 0.015; pη(2) = 194), NN50% (p = 0.008; pη(2) = 0.224), and LF% (p = 0.014; pη(2) = 0.196), and moderate effects with respect HF% (p = 0.099; pη(2) = 0.094), with PLA subjects showing a higher increase in HR and SDNN and a higher decrease in RMSSD, NN50, LF and HF than subjects in the ESC condition. Thus, ESC treatment significantly blunted the autonomic reactivity to CCK-4. Secondary analysis indicated no effect of the 5-HTTLPR polymorphism on CCK-4-induced autonomic response. CONCLUSIONS: Our results support findings suggesting an effect of SSRI treatment on autonomic regulation and provide evidence that ESC treatment is associated with blunted autonomic reactivity in healthy men.
[Mh] Termos MeSH primário: Sistema Nervoso Autônomo/efeitos dos fármacos
Citalopram/farmacologia
Frequência Cardíaca/efeitos dos fármacos
Inibidores da Captação de Serotonina/farmacologia
[Mh] Termos MeSH secundário: Administração Intravenosa
Adulto
Sistema Nervoso Autônomo/fisiologia
Citalopram/administração & dosagem
Estudos Cross-Over
Método Duplo-Cego
Hormônios Gastrointestinais/administração & dosagem
Hormônios Gastrointestinais/farmacologia
Voluntários Saudáveis
Seres Humanos
Masculino
Distribuição Aleatória
Inibidores da Captação de Serotonina/administração & dosagem
Tetragastrina/administração & dosagem
Tetragastrina/farmacologia
Fatores de Tempo
Resultado do Tratamento
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Gastrointestinal Hormones); 0 (Serotonin Uptake Inhibitors); 0DHU5B8D6V (Citalopram); 0OL293AV80 (Tetragastrin)
[Em] Mês de entrada:1512
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:141219
[St] Status:MEDLINE


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[PMID]:25391026
[Au] Autor:Doyle JR; Harwood BN; Krishnaji ST; Krishnamurthy VM; Lin WE; Fortin JP; Kumar K; Kopin AS
[Ad] Endereço:Tufts Medical Center, Molecular Cardiology Research Institute, Molecular Pharmacology Research Center, Boston, Massachusetts, United States of America.
[Ti] Título:A two-step strategy to enhance activity of low potency peptides.
[So] Source:PLoS One;9(11):e110502, 2014.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Novel strategies are needed to expedite the generation and optimization of peptide probes targeting G protein-coupled receptors (GPCRs). We have previously shown that membrane tethered ligands (MTLs), recombinant proteins comprised of a membrane anchor, an extracellular linker, and a peptide ligand can be used to identify targeted receptor modulators. Although MTLs provide a useful tool to identify and/or modify functionally active peptides, a major limitation of this strategy is the reliance on recombinant protein expression. We now report the generation and pharmacological characterization of prototype peptide-linker-lipid conjugates, synthetic membrane anchored ligands (SMALs), which are designed as mimics of corresponding MTLs. In this study, we systematically compare the activity of selected peptides as MTLs versus SMALs. As prototypes, we focused on the precursor proteins of mature Substance P (SubP) and Cholecystokinin 4 (CCK4), specifically non-amidated SubP (SubP-COOH) and glycine extended CCK4 (CCK4-Gly-COOH). As low affinity soluble peptides these ligands each presented a challenging test case for assessment of MTL/SMAL technology. For each ligand, MTLs and corresponding SMALs showed agonist activity and comparable subtype selectivity. In addition, our results illustrate that membrane anchoring increases ligand potency. Furthermore, both MTL and SMAL induced signaling can be blocked by specific non-peptide antagonists suggesting that the anchored constructs may be orthosteric agonists. In conclusion, MTLs offer a streamlined approach for identifying low activity peptides which can be readily converted to higher potency SMALs. The ability to recapitulate MTL activity with SMALs extends the utility of anchored peptides as probes of GPCR function.
[Mh] Termos MeSH primário: Peptídeos/química
Receptores Acoplados a Proteínas-G/química
[Mh] Termos MeSH secundário: Glicina/química
Células HEK293
Seres Humanos
Ligantes
Piperidinas/química
Plasmídeos/metabolismo
Estrutura Terciária de Proteína
Receptores da Neurocinina-1/química
Proteínas Recombinantes/química
Transdução de Sinais
Substância P/química
Tetragastrina/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Ligands); 0 (Peptides); 0 (Piperidines); 0 (Receptors, G-Protein-Coupled); 0 (Receptors, Neurokinin-1); 0 (Recombinant Proteins); 0OL293AV80 (Tetragastrin); 136982-36-0 (3-(2-methoxybenzylamino)-2-phenylpiperidine); 33507-63-0 (Substance P); TE7660XO1C (Glycine)
[Em] Mês de entrada:1507
[Cu] Atualização por classe:161019
[Lr] Data última revisão:
161019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:141113
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0110502


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[PMID]:25106129
[Au] Autor:Desai SJ; Borkar CD; Nakhate KT; Subhedar NK; Kokare DM
[Ad] Endereço:Department of Anatomy & Cell Biology, University of Western Ontario, Ontario, Canada.
[Ti] Título:Neuropeptide Y attenuates anxiety- and depression-like effects of cholecystokinin-4 in mice.
[So] Source:Neuroscience;277:818-30, 2014 Sep 26.
[Is] ISSN:1873-7544
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We investigated the involvement of neuropeptide Y (NPY) in the modulation of cholecystokinin-4 (CCK-4)-evoked anxiety and depression. Adult male mice were injected with vehicle, CCK-4, NPY, NPY Y1 receptor agonist [Leu(31), Pro(34)]-NPY or antagonist BIBP3226, via intracerebroventricular route, and subjected to social interaction or forced swim test (FST) for the evaluation of anxiety- and depression-like phenotypes, respectively. To assess the interactions between the two systems, if any, NPYergic agents were administered prior to CCK-4 and the animals were subjected to these behavioral tests. Treatment with CCK-4 or BIBP3226 dose-dependently reduced social interaction time, while NPY or [Leu(31), Pro(34)]-NPY produced opposite effect. CCK-4 treatment increased immobility time in FST. This effect was reversed by NPY and [Leu(31), Pro(34)]-NPY, although BIBP3226 per se did not alter the immobility time. In a combination study, the anxiogenic or depressive effects of CCK-4 were attenuated by NPY or [Leu(31), Pro(34)]-NPY and potentiated by BIBP3226. The brains of CCK-4 treated rats were processed for NPY immunohistochemistry. Following CCK-4 treatment, the nucleus accumbens shell (AcbSh), ventral part of lateral division of the bed nucleus of stria terminalis (BSTLV), hypothalamic paraventricular nucleus and locus coeruleus showed a reduction in NPY-immunoreactive fibers. Population of NPY-immunopositive cells was also decreased in the AcbSh, BSTLV, prefrontal cortex and hypothalamic arcuate nucleus (ARC). However, NPY-immunoreaction in the fibers of the ARC and cells of the central nucleus of amygdala was unchanged. We conclude that, inhibition of NPY signaling in the brain by CCK-4 might be causal to anxiety- and depression-like behaviors.
[Mh] Termos MeSH primário: Ansiedade/fisiopatologia
Encéfalo/fisiopatologia
Depressão/fisiopatologia
Neuropeptídeo Y/metabolismo
Receptores de Neuropeptídeo Y/metabolismo
Tetragastrina/metabolismo
[Mh] Termos MeSH secundário: Animais
Ansiolíticos/farmacologia
Ansiedade/tratamento farmacológico
Arginina/análogos & derivados
Arginina/farmacologia
Encéfalo/efeitos dos fármacos
Depressão/tratamento farmacológico
Modelos Animais de Doenças
Relação Dose-Resposta a Droga
Imuno-Histoquímica
Masculino
Camundongos
Atividade Motora/efeitos dos fármacos
Atividade Motora/fisiologia
Neuropeptídeo Y/administração & dosagem
Testes Neuropsicológicos
Psicotrópicos/administração & dosagem
Receptores de Neuropeptídeo Y/agonistas
Receptores de Neuropeptídeo Y/antagonistas & inibidores
Comportamento Social
Natação
Tetragastrina/administração & dosagem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Anxiety Agents); 0 (BIBP 3226); 0 (Neuropeptide Y); 0 (Npy1r protein, mouse); 0 (Psychotropic Drugs); 0 (Receptors, Neuropeptide Y); 0OL293AV80 (Tetragastrin); 94ZLA3W45F (Arginine)
[Em] Mês de entrada:1506
[Cu] Atualização por classe:140915
[Lr] Data última revisão:
140915
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140810
[St] Status:MEDLINE


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[PMID]:24342768
[Au] Autor:Agorastos A; Kellner M; Stiedl O; Muhtz C; Becktepe JS; Wiedemann K; Demiralay C
[Ad] Endereço:Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Martini Str. 52, D-20246 Hamburg, Germany. Electronic address: aagorast@uke.uni-hamburg.de.
[Ti] Título:The 5-HTTLPR genotype modulates heart rate variability and its adjustment by pharmacological panic challenge in healthy men.
[So] Source:J Psychiatr Res;50:51-8, 2014 Mar.
[Is] ISSN:1879-1379
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Abnormal serotonin transporter (5-HTT) function and autonomic nervous system (ANS) dysregulation has been proposed in panic disorder. However, in contrast to hypothalamo-pituitary-adrenocortical (HPA) functioning, ANS reactivity during panic response has yet not been investigated in humans with respect to the 5-HTT genotype. The present study assessed the influence of challenging by cholecystokinin tetrapeptide (CCK-4) on heart rate variability (HRV) measures, to monitor autonomic reactivity and its relationship to 5-HTT-linked polymorphic region (5-HTTLPR) genotypes. We hypothesized substantial effects of the 5-HTTLPR genotype on autonomic reactivity. We studied 30 healthy young men, 15 of each with the long/long (l/l) or short/short (s/s) genotype for the 5-HTTLPR. All participants received an intravenous application of 50 µg CCK-4. HRV measures were assessed in both groups at baseline and immediately after CCK-4 application. Our results indicated lower parasympathetic activity in s/s carriers during baseline, time and frequency domain measures. CCK-4 application significantly enhanced the sympathetic tone in both groups, leading to diminished group differences. A significant treatment by genotype effect indicated reduced autonomic reactivity to CCK-4 challenge in the s/s compared to l/l carriers. Our findings show enhanced sympathetic and/or diminished cardiac vagal activity under basal conditions and blunted autonomic reactivity in s/s vs. l/l carriers. Our study provides novel data supporting claims that the s/s genotype represents a genetic vulnerability factor associated with inadequate hyporeactivity to stress and extends current knowledge on the impact of the central serotonergic activity on the sympathoadrenal pathway.
[Mh] Termos MeSH primário: Fármacos do Sistema Nervoso Autônomo/farmacologia
Frequência Cardíaca/efeitos dos fármacos
Frequência Cardíaca/genética
Proteínas da Membrana Plasmática de Transporte de Serotonina/genética
Tetragastrina/farmacologia
[Mh] Termos MeSH secundário: Análise de Variância
Eletrocardiografia
Genótipo
Seres Humanos
Masculino
Pânico
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Autonomic Agents); 0 (SLC6A4 protein, human); 0 (Serotonin Plasma Membrane Transport Proteins); 0OL293AV80 (Tetragastrin)
[Em] Mês de entrada:1410
[Cu] Atualização por classe:140124
[Lr] Data última revisão:
140124
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:131218
[St] Status:MEDLINE


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[PMID]:24397028
[Au] Autor:Gudasheva TA; Lezina VP; Kir'ianova EP; Deeva OA; Kolik LG; Seredenin SB
[Ti] Título:[The study of biologically active conformation of cholecystokinin-4 dipeptide analog GB-115].
[So] Source:Bioorg Khim;39(3):293-302, 2013 May-Jun.
[Is] ISSN:0132-3423
[Cp] País de publicação:Russia (Federation)
[La] Idioma:rus
[Ab] Resumo:The conformational analysis with 1H NMR spectroscopy method in solution and the structure-activity relationship study of a series sterically restricted analogs allowed to detect the possible biologically active conformation of N-(6-phenylhexanoyl)glycyl-tryptophan amide (GB-115), a highly active dipeptide cholecystokinin-4 analog with anxiolytic activity. The structure-activity relationship study of GB-115 and the series of its' glycine- and proline-containing analogs with different C-terminal substitute detected the anxiolytic activity of compounds with beta-turn like conformation and inactivity of compounds with gamma-turn like conformation. So, the GB-115 biologically active conformation is beta-turn. The results of nuclear Overhauser effect study permitted to qualify the betaII-turn conformation as GB-115 biologically active conformation. The following synthesis of sterically restricted GB-115 analogs (2S)-2-{(3R)-3-[(6-phenylhexanoyl)amino]-2-oxopyrrolidin-1-yl}-3-(1H-indol-3-yl)propionic acid ethyl ester, N-(6-phenylhexanoyl)glycyl-N(alpha)(methyl)-tryptophan ethyl ester, (2S)-2-[10,11-dihydro-5H-dibenzo[b,f] azepin-5-carbonyl)-amino]-3-(1H-indol-3-yl)propionic acid methyl ester and (2S)-2-[({3-[(ethoxycarbonyl)amino]-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl}carbonyl)amino]-3-(1H-indol-3-yl)propionic acid methyl ester confirmed the estimated type of GB-115 biologically active conformation.
[Mh] Termos MeSH primário: Ansiedade/tratamento farmacológico
Dipeptídeos/química
Relação Estrutura-Atividade
Tetragastrina/química
[Mh] Termos MeSH secundário: Animais
Ansiolíticos/química
Ansiolíticos/farmacologia
Ansiedade/patologia
Dipeptídeos/síntese química
Dipeptídeos/farmacologia
Glicina/química
Seres Humanos
Espectroscopia de Ressonância Magnética
Prolina/química
Estrutura Secundária de Proteína
Ratos
Tetragastrina/análogos & derivados
Tetragastrina/farmacologia
Triptofano/química
[Pt] Tipo de publicação:ENGLISH ABSTRACT; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Anxiety Agents); 0 (Dipeptides); 0 (GB-115); 0OL293AV80 (Tetragastrin); 8DUH1N11BX (Tryptophan); 9DLQ4CIU6V (Proline); TE7660XO1C (Glycine)
[Em] Mês de entrada:1402
[Cu] Atualização por classe:140108
[Lr] Data última revisão:
140108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140109
[St] Status:MEDLINE


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[PMID]:24130989
[Au] Autor:Kolik LG; Konstantinopolsky MA; Ryibina IV; Povarnina PY; Gudasheva TA; Seredenin SB
[Ad] Endereço:V. V. Zakusov Institute of Pharmacology, Russian Academy of Medical Sciences, Moscow, Russia. lgkolik@mail.ru.
[Ti] Título:Anxiolytic activity of dipeptide GB-115 after oral administration.
[So] Source:Bull Exp Biol Med;155(2):200-3, 2013 Jun.
[Is] ISSN:1573-8221
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The anxiolytic effects of GB-115, a retroanalogue of cholecystokinin-4, administered orally to outbred and inbred animals with different level of emotionality, were studied in the open field test and elevated plus-maze test. The anxiolytic effect of talanax was observed in outbred mice (0.1-0.5 mg/kg) and in inbred BALB/c mice (0.1 and 5.0 mg/kg) in the open field test. GB-115 increased the time of entries into open arms in outbred rats (0.5-0.7 mg/kg) and in BALB/c mice (0.1 mg/kg). These data confirmed the dependence of GB-115 effect on the phenotype of emotional stress response and demonstrated a shift of anxiolytic doses of the preparation from 0.006-0.100 mg/kg in intraperitoneal administration to 0.1-5.0 mg/kg in oral treatment.
[Mh] Termos MeSH primário: Ansiolíticos/farmacologia
Colecistocinina/farmacologia
Dipeptídeos/farmacologia
Estresse Psicológico/tratamento farmacológico
Tetragastrina/farmacologia
[Mh] Termos MeSH secundário: Administração Oral
Animais
Comportamento Animal/efeitos dos fármacos
Colecistocinina/análogos & derivados
Masculino
Aprendizagem em Labirinto/efeitos dos fármacos
Camundongos
Camundongos Endogâmicos BALB C
Camundongos Endogâmicos C57BL
Ratos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Anxiety Agents); 0 (Dipeptides); 0 (GB-115); 0OL293AV80 (Tetragastrin); 9011-97-6 (Cholecystokinin)
[Em] Mês de entrada:1407
[Cu] Atualização por classe:131016
[Lr] Data última revisão:
131016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:131017
[St] Status:MEDLINE


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[PMID]:23463151
[Au] Autor:Zwanzger P; Zavorotnyy M; Gencheva E; Diemer J; Kugel H; Heindel W; Ruland T; Ohrmann P; Arolt V; Domschke K; Pfleiderer B
[Ad] Endereço:Mood and Anxiety Disorders Research Unit, Department of Psychiatry and Psychotherapy, University of Muenster, Muenster, Germany. zwanzger@ukmuenster.de
[Ti] Título:Acute shift in glutamate concentrations following experimentally induced panic with cholecystokinin tetrapeptide--a 3T-MRS study in healthy subjects.
[So] Source:Neuropsychopharmacology;38(9):1648-54, 2013 Aug.
[Is] ISSN:1740-634X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:According to preclinical studies, glutamate has been implicated in the pathogenesis of anxiety. In order to elucidate the role of glutamate in anxiety and panic in humans, brain glutamate+glutamine (Glx) levels were measured during cholecystokinin-tetrapeptide (CCK-4)-induced panic using magnetic resonance spectroscopy (MRS). Eighteen healthy subjects underwent a CCK-4 challenge. MR spectra were obtained from the anterior cingulate cortex (ACC) using a single voxel point-resolved spectroscopy method and analyzed using LCModel. A combined fitting of Glx was performed. Panic was assessed using the Acute Panic Inventory (API) and Panic Symptom Scale (PSS) scores. Moreover, hypothalamic-pituitary-adrenal axis stimulation was monitored throughout the challenge. There was a significant panic response following CCK-4 as revealed by a marked increase in both the panic scores (API: F(1,17)=149.41; p<0.0001; PSS: F(1,17)=88.03; p<0.0001) and heart rate (HR: F(1,17)=72.79; p<0.0001). MRS measures showed a significant increase of brain Glx/creatine (Glx/Cr) levels peaking at 2-10 min after challenge (F(1,17)=15.94; p=0.001). There was also a significant increase in CCK-4-related cortisol release (F(6,11)=8.68; p=0.002). Finally, significant positive correlations were found between baseline Glx/Cr and both APImax (r=0.598; p=0.009) and maximum heart rate (HR(max)) during challenge (r=0.519; p=0.027). Our results suggest that CCK-4-induced panic is accompanied by a significant glutamate increase in the bilateral ACC. The results add to the hypothesis of a disturbance of the inhibitory-excitatory equilibrium and suggest that apart from static alterations rapid and dynamic neurochemical changes might also be relevant for the neural control of panic attacks.
[Mh] Termos MeSH primário: Ácido Glutâmico/metabolismo
Transtorno de Pânico/metabolismo
[Mh] Termos MeSH secundário: Hormônio Adrenocorticotrópico/sangue
Adulto
Creatina/metabolismo
Neuroimagem Funcional
Glutamina/metabolismo
Giro do Cíngulo/metabolismo
Frequência Cardíaca
Seres Humanos
Hidrocortisona/sangue
Sistema Hipotálamo-Hipofisário/metabolismo
Masculino
Transtorno de Pânico/sangue
Transtorno de Pânico/induzido quimicamente
Sistema Hipófise-Suprarrenal/metabolismo
Escalas de Graduação Psiquiátrica
Tetragastrina
[Pt] Tipo de publicação:CLINICAL TRIAL; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0OL293AV80 (Tetragastrin); 0RH81L854J (Glutamine); 3KX376GY7L (Glutamic Acid); 9002-60-2 (Adrenocorticotropic Hormone); MU72812GK0 (Creatine); WI4X0X7BPJ (Hydrocortisone)
[Em] Mês de entrada:1404
[Cu] Atualização por classe:150311
[Lr] Data última revisão:
150311
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:130307
[St] Status:MEDLINE
[do] DOI:10.1038/npp.2013.61


  10 / 535 MEDLINE  
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[PMID]:23059050
[Au] Autor:Leicht G; Mulert C; Eser D; Sämann PG; Ertl M; Laenger A; Karch S; Pogarell O; Meindl T; Czisch M; Rupprecht R
[Ad] Endereço:Psychiatry Neuroimaging Branch, University Medical Center Hamburg-Eppendorf, Department of Psychiatry and Psychotherapy, Psychiatry Neuroimiaging Branch, Hamburg, Germany. g.leicht@uke.de
[Ti] Título:Benzodiazepines counteract rostral anterior cingulate cortex activation induced by cholecystokinin-tetrapeptide in humans.
[So] Source:Biol Psychiatry;73(4):337-44, 2013 Feb 15.
[Is] ISSN:1873-2402
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Benzodiazepines modulate γ-aminobutyric acid type A (GABA(A)) receptors throughout the brain. However, it is not fully understood which brain regions within anxiety-related brain circuits are really responsible for their anxiolytic effects and how these regions interact. METHODS: We investigated whether the benzodiazepine alprazolam affects activity in distinct brain regions within anxiety-related circuits during an experimental anxiety paradigm by means of functional magnetic resonance imaging (fMRI). Panic symptoms were elicited by a bolus injection of the neuropeptide cholecystokinin-tetrapeptide (CCK-4) in 16 healthy male subjects in a double-blind, placebo-controlled design. Functional brain activation patterns were determined before and during the CCK-4-challenge without pretreatment and after treatment with either placebo or 1 mg alprazolam. RESULTS: The CCK-4 induced anxiety and elicited widely distributed activation patterns in anxiety-related brain circuits, especially in the rostral anterior cingulate cortex (rACC), which was attenuated after alprazolam treatment. In contrast to placebo, alprazolam abolished the activation of the rACC after challenge with CCK-4 (p<.005, corrected for multiple comparisons) and increased functional connectivity between the rACC and other anxiety-related brain regions such as amygdala and prefrontal cortex. Moreover, the reduction in the CCK-4 induced activation of the rACC correlated with the anxiolytic effect of alprazolam (r(p) = .52; p = .04). CONCLUSIONS: These findings put forward the rACC as a target for benzodiazepines and suggest that the CCK-4/fMRI paradigm might represent a human translational model for the investigation of anxiolytic drugs.
[Mh] Termos MeSH primário: Alprazolam/farmacologia
Ansiolíticos/farmacologia
Ansiedade/tratamento farmacológico
Moduladores GABAérgicos/farmacologia
Giro do Cíngulo/efeitos dos fármacos
[Mh] Termos MeSH secundário: Adulto
Alprazolam/uso terapêutico
Ansiolíticos/uso terapêutico
Ansiedade/induzido quimicamente
Ansiedade/fisiopatologia
Encéfalo/efeitos dos fármacos
Encéfalo/fisiopatologia
Mapeamento Encefálico
Método Duplo-Cego
Moduladores GABAérgicos/uso terapêutico
Giro do Cíngulo/fisiopatologia
Seres Humanos
Processamento de Imagem Assistida por Computador
Imagem por Ressonância Magnética
Masculino
Tetragastrina
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Anxiety Agents); 0 (GABA Modulators); 0OL293AV80 (Tetragastrin); YU55MQ3IZY (Alprazolam)
[Em] Mês de entrada:1307
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:121013
[St] Status:MEDLINE



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