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Registro de Ensaios Clínicos
Registro de Ensaios Clínicos
Registro de Ensaios Clínicos
Registro de Ensaios Clínicos
Registro de Ensaios Clínicos
Registro de Ensaios Clínicos
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[PMID]:29318278
[Au] Autor:Atri A; Frölich L; Ballard C; Tariot PN; Molinuevo JL; Boneva N; Windfeld K; Raket LL; Cummings JL
[Ad] Endereço:Ray Dolby Brain Health Center, California Pacific Medical Center, San Francisco.
[Ti] Título:Effect of Idalopirdine as Adjunct to Cholinesterase Inhibitors on Change in Cognition in Patients With Alzheimer Disease: Three Randomized Clinical Trials.
[So] Source:JAMA;319(2):130-142, 2018 01 09.
[Is] ISSN:1538-3598
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Importance: New therapeutic approaches for Alzheimer disease (AD) are needed. Objective: To assess whether idalopirdine, a selective 5-hydroxytryptamine-6 receptor antagonist, is effective for symptomatic treatment of mild to moderate AD. Design, Setting, and Participants: Three randomized clinical trials that included 2525 patients aged 50 years or older with mild to moderate AD (study 1: n = 933 patients at 119 sites; study 2: n = 858 at 158 sites; and study 3: n = 734 at 126 sites). The 24-week studies were conducted from October 2013 to January 2017; final follow-up on January 12, 2017. Interventions: Idalopirdine (10, 30, or 60 mg/d) or placebo added to cholinesterase inhibitor treatment (donepezil in studies 1 and 2; donepezil, rivastigmine, or galantamine in study 3). Main Outcomes and Measures: Primary end point in all 3 studies: change in cognition total score (range, 0-70; a lower score indicates less impairment) from baseline to 24 weeks measured by the 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog); key secondary end points: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Scale and 23-item Activities of Daily Living Inventory scores. Dose group efficacy required a significant benefit over placebo for the primary end point and 1 or more key secondary end points. Safety data and adverse event profiles were recorded. Results: Among 2525 patients randomized in the 3 trials (mean age, 74 years; mean baseline ADAS-Cog total score, 26; between 62% and 65% of participants were women), 2254 (89%) completed the studies. In study 1, the mean change in ADAS-Cog total score between baseline and 24 weeks was 0.37 for the 60-mg dose of idalopirdine group, 0.61 for the 30-mg dose group, and 0.41 for the placebo group (adjusted mean difference vs placebo, 0.05 [95% CI, -0.88 to 0.98] for the 60-mg dose group and 0.33 [95% CI, -0.59 to 1.26] for the 30-mg dose group). In study 2, the mean change in ADAS-Cog total score between baseline and 24 weeks was 1.01 for the 30-mg dose of idalopirdine group, 0.53 for the 10-mg dose group, and 0.56 for the placebo group (adjusted mean difference vs placebo, 0.63 [95% CI, -0.38 to 1.65] for the 30-mg dose group; given the gated testing strategy and the null findings at the 30-mg dose, statistical comparison of the 10-mg dose was not performed). In study 3, the mean change in ADAS-Cog total score between baseline and 24 weeks was 0.38 for the 60-mg dose of idalopirdine group and 0.82 for the placebo group (adjusted mean difference vs placebo, -0.55 [95% CI, -1.45 to 0.36]). Treatment-emergent adverse events occurred in between 55.4% and 69.7% of participants in the idalopirdine groups vs between 56.7% and 61.4% of participants in the placebo groups. Conclusions and Relevance: In patients with mild to moderate AD, the use of idalopirdine compared with placebo did not improve cognition over 24 weeks of treatment. These findings do not support the use of idalopirdine for the treatment of AD. Trial Registration: clinicaltrials.gov Identifiers: NCT01955161, NCT02006641, and NCT02006654.
[Mh] Termos MeSH primário: Doença de Alzheimer/tratamento farmacológico
Benzilaminas/uso terapêutico
Inibidores da Colinesterase/uso terapêutico
Indóis/uso terapêutico
Antagonistas da Serotonina/uso terapêutico
[Mh] Termos MeSH secundário: Acidentes por Quedas
Idoso
Idoso de 80 Anos ou mais
Doença de Alzheimer/psicologia
Benzilaminas/administração & dosagem
Benzilaminas/efeitos adversos
Inibidores da Colinesterase/efeitos adversos
Cognição/efeitos dos fármacos
Relação Dose-Resposta a Droga
Método Duplo-Cego
Quimioterapia Combinada
Feminino
Galantamina/uso terapêutico
Seres Humanos
Indanos/uso terapêutico
Indóis/administração & dosagem
Indóis/efeitos adversos
Masculino
Meia-Idade
Piperidinas/uso terapêutico
Rivastigmina/uso terapêutico
Antagonistas da Serotonina/administração & dosagem
Antagonistas da Serotonina/efeitos adversos
Falha de Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 ((2-(6-fluoro-1H-indol-3-yl)-ethyl)-(3-(2,2,3,3-tetrafluoropropoxy)benzyl)amine); 0 (Benzylamines); 0 (Cholinesterase Inhibitors); 0 (Indans); 0 (Indoles); 0 (Piperidines); 0 (Serotonin Antagonists); 0D3Q044KCA (Galantamine); 8SSC91326P (donepezil); PKI06M3IW0 (Rivastigmine)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180311
[Lr] Data última revisão:
180311
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180111
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1001/jama.2017.20373


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[PMID]:29467153
[Au] Autor:Le Couteur DG; Bateman B; Brayne C
[Ad] Endereço:Centre for Education and Research on Ageing, Concord Hospital and University of Sydney, Sydney, Australia.
[Ti] Título:Idalopirdine: another disappointment for people with dementia.
[So] Source:BMJ;360:k753, 2018 02 21.
[Is] ISSN:1756-1833
[Cp] País de publicação:England
[La] Idioma:eng
[Mh] Termos MeSH primário: Benzilaminas/uso terapêutico
Demência/tratamento farmacológico
Indóis/uso terapêutico
Antagonistas da Serotonina/uso terapêutico
[Mh] Termos MeSH secundário: Ensaios Clínicos como Assunto
Seres Humanos
Falha de Tratamento
[Pt] Tipo de publicação:EDITORIAL
[Nm] Nome de substância:
0 ((2-(6-fluoro-1H-indol-3-yl)-ethyl)-(3-(2,2,3,3-tetrafluoropropoxy)benzyl)amine); 0 (Benzylamines); 0 (Indoles); 0 (Serotonin Antagonists)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180223
[St] Status:MEDLINE
[do] DOI:10.1136/bmj.k753


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[PMID]:28458421
[Au] Autor:Saikia B; Barua CC; Haloi P; Patowary P
[Ad] Endereço:Department of Pharmacology and Toxicology, College of Veterinary Science, Assam Agricultural University, Guwahati, Assam, India.
[Ti] Título:Anticholinergic, antihistaminic, and antiserotonergic activity of n-hexane extract of seeds on isolated tissue preparations: An study.
[So] Source:Indian J Pharmacol;49(1):42-48, 2017 Jan-Feb.
[Is] ISSN:1998-3751
[Cp] País de publicação:India
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: The aim of this study was to evaluate anticholinergic, antihistaminic, and antiserotonergic activity of the n-hexane extract of the seeds of (ZAHE) on isolated ileum of rat and guinea pig and fundus of rat. MATERIALS AND METHODS: ZAHE was prepared using soxhlet extraction and cumulative concentration response curves were constructed using various doses on the tissues for acetylcholine (ACh), 5-hydroxytryptamine (5-HT), and histamine with or without n-hexane extract. Atropine, ketanserin, and pheniramine maleate were used as antagonists for ACh, serotonin, and histamine, respectively. RESULTS: ZAHE-induced concentration-dependent inhibition of isolated ileum and fundus in rat and ileum of guinea pig. The half maximal effective concentration (EC ) of ACh in the presence of atropine (10 M; < 0.05) and ZAHE (1000 µg/ml; < 0.01) was significantly higher than EC of ACh alone. The EC of 5-HT in the presence of ketanserin (10 M; < 0.01) and ZAHE (1000 µg/ml; < 0.05) was higher than EC of 5-HT alone. Similarly, the EC of histamine in the presence of pheniramine maleate (10 M; < 0.01) and ZAHE (300 µg/ml; < 0.01 and 1000 µg/ml; < 0.05) was also significantly higher than EC of histamine alone. CONCLUSION: From the study, it was observed that ZAHE shows significant anticholinergic, antiserotonergic, and antihistaminic activity. The study provides sufficient evidence that the seeds can be used in gastric disorders, cough, chest infection, etc., as per folklore claims.
[Mh] Termos MeSH primário: Antagonistas Colinérgicos/farmacologia
Antagonistas dos Receptores Histamínicos/farmacologia
Extratos Vegetais/farmacologia
Antagonistas da Serotonina/farmacologia
Zanthoxylum/química
[Mh] Termos MeSH secundário: Acetilcolina/metabolismo
Animais
Antagonistas Colinérgicos/administração & dosagem
Antagonistas Colinérgicos/isolamento & purificação
Relação Dose-Resposta a Droga
Fundo Gástrico/efeitos dos fármacos
Fundo Gástrico/metabolismo
Cobaias
Hexanos/química
Histamina/metabolismo
Antagonistas dos Receptores Histamínicos/administração & dosagem
Antagonistas dos Receptores Histamínicos/isolamento & purificação
Íleo/efeitos dos fármacos
Íleo/metabolismo
Masculino
Extratos Vegetais/administração & dosagem
Ratos
Ratos Wistar
Sementes
Serotonina/metabolismo
Antagonistas da Serotonina/administração & dosagem
Antagonistas da Serotonina/isolamento & purificação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cholinergic Antagonists); 0 (Hexanes); 0 (Histamine Antagonists); 0 (Plant Extracts); 0 (Serotonin Antagonists); 2DDG612ED8 (n-hexane); 333DO1RDJY (Serotonin); 820484N8I3 (Histamine); N9YNS0M02X (Acetylcholine)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171229
[Lr] Data última revisão:
171229
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE
[do] DOI:10.4103/0253-7613.201025


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[PMID]:29183322
[Au] Autor:Pan J; Xu Y; Song H; Zhou X; Yao Z; Ji G
[Ad] Endereço:Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China.
[Ti] Título:Extracts of Zuo Jin Wan, a traditional Chinese medicine, phenocopies 5-HTR1D antagonist in attenuating Wnt/ß-catenin signaling in colorectal cancer cells.
[So] Source:BMC Complement Altern Med;17(1):506, 2017 Nov 28.
[Is] ISSN:1472-6882
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: In vitro and in vivo studies have shown that Zuo Jin Wan (ZJW), a herbal formula of traditional Chinese medicine (TCM), possessed anticancer properties. However, the underlying mechanism for the action of ZJW remains unclear. Various subtypes of 5-Hydroxytryptamine receptor (5-HTR) have been shown to play a role in carcinogenesis and cancer metastasis. 5-HTR1D, among the subtypes, is highly expressed in colorectal cancer (CRC) cell lines and tissues. The present study aimed at investigating effect of ZJW extracts on the biological function of CRC cells, the expression of 5-HTR1D, and molecules of Wnt/ß-catenin signaling pathway. METHODS: In this study, the effect of ZJW extracts on 5-HTR1D expression and Wnt/ß-catenin signaling pathway were investigated and contrasted with GR127935 (GR), a known 5-HTR1D antagonist, using the CRC cell line SW403. The cells were respectively treated with GR127935 and different doses of ZJW extracts. Proliferation, apoptosis, migration, and invasion of SW403 cells were compared between ZJW and GR127935 treatments. The expression of 5-HTR1D and signaling molecules involved in the canonic Wnt/ß-catenin pathway were determined by Western blot analysis. RESULTS: After ZJW extracts treatment and GR127935 treatment, G1 arrest in cell cycle of SW403 was increased. Cell apoptosis was pronounced, and cell migration and invasion were suppressed. SW403 cells showed a dose-dependently decreased expression of 5-HTR1D, meanwhile, ß-catenin level was significantly decreased in nucleus of cells cultured with GR127935. Treatment of ZJW extracts dose-dependently resulted in decreased 5-HTR1D and a concomitant reduction in the Wnt/ß-catenin signal transduction, an effect indistinguishable from GR127935 treatment. CONCLUSION: The anticancer activity of ZJW extracts may be partially achieved through attenuation of the 5-HTR1D-Wnt/ß-catenin signaling pathway.
[Mh] Termos MeSH primário: Neoplasias Colorretais/metabolismo
Medicamentos de Ervas Chinesas/farmacologia
Receptores de Serotonina/metabolismo
Antagonistas da Serotonina/farmacologia
Via de Sinalização Wnt/efeitos dos fármacos
[Mh] Termos MeSH secundário: Apoptose/efeitos dos fármacos
Linhagem Celular Tumoral
Movimento Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Medicamentos de Ervas Chinesas/química
Seres Humanos
Receptores de Serotonina/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Drugs, Chinese Herbal); 0 (Receptors, Serotonin); 0 (Serotonin Antagonists); 0 (Zuo-Jin-Wan)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171219
[Lr] Data última revisão:
171219
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171130
[St] Status:MEDLINE
[do] DOI:10.1186/s12906-017-2006-7


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[PMID]:29187483
[Au] Autor:Sento S; Kitamura N; Yamamoto T; Nakashiro K; Hamakawa H; Ibaragi S; Sasaki A; Takamaru N; Miyamoto Y; Kodani I; Ryoke K; Mishima K; Ueyama Y; ORAL CANCER STUDY GROUP OF CHUGOKU-SHIKOKU
[Ad] Endereço:Department of Oral and Maxillofacial Surgery, Kochi Medical School, Kochi University, Nankoku, Japan shinya-sento@kochi-u.ac.jp.
[Ti] Título:Palonosetron Prevents Highly Emetogenic Chemotherapy-induced Nausea and Vomiting in Oral Cancer Patients.
[So] Source:Anticancer Res;37(12):6977-6981, 2017 12.
[Is] ISSN:1791-7530
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/AIM: To evaluate the efficacy of palonosetron in preventing acute and delayed nausea and vomiting in patients receiving highly emetogenic chemotherapy (HEC) in oral cancer patients. PATIENTS AND METHODS: Oral cancer patients receiving HEC were enrolled; among the 40 patients, 87 courses of chemotherapy were administered. On day 1, 0.75 mg palonosetron was intravenously administrated just before chemotherapy. RESULTS: The primary endpoint was the proportion of patients with a complete response (CR) and the secondary endpoint was the proportion of patients with complete control (CC) during the acute and delayed phase. During the acute phase, 86 of 87 courses (98.9%) had CR and 84 of 87 courses (96.6%) had CC. During the delayed phase, 84 of 87 courses (96.6%) had CR and 70 of 87 courses (80.5%) had CC. CONCLUSION: Palonosetron is effective at preventing HEC-induced chemotherapy-induced nausea and vomiting (CINV) in oral cancer chemotherapeutic regimens in the acute and delayed phases.
[Mh] Termos MeSH primário: Antineoplásicos/uso terapêutico
Isoquinolinas/uso terapêutico
Neoplasias Bucais/tratamento farmacológico
Náusea/prevenção & controle
Quinuclidinas/uso terapêutico
Vômito/prevenção & controle
[Mh] Termos MeSH secundário: Administração Intravenosa
Adulto
Idoso
Idoso de 80 Anos ou mais
Antineoplásicos/efeitos adversos
Cisplatino/administração & dosagem
Cisplatino/efeitos adversos
Quimioterapia Combinada
Feminino
Seres Humanos
Isoquinolinas/administração & dosagem
Masculino
Meia-Idade
Náusea/induzido quimicamente
Quinuclidinas/administração & dosagem
Antagonistas da Serotonina/administração & dosagem
Antagonistas da Serotonina/uso terapêutico
Resultado do Tratamento
Vômito/induzido quimicamente
[Pt] Tipo de publicação:CLINICAL TRIAL; JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Isoquinolines); 0 (Quinuclidines); 0 (Serotonin Antagonists); 5D06587D6R (palonosetron); Q20Q21Q62J (Cisplatin)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171211
[Lr] Data última revisão:
171211
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171201
[St] Status:MEDLINE


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[PMID]:28805659
[Au] Autor:Lord CC; Wyler SC; Wan R; Castorena CM; Ahmed N; Mathew D; Lee S; Liu C; Elmquist JK
[Ad] Endereço:Division of Hypothalamic Research, Department of Internal Medicine, and.
[Ti] Título:The atypical antipsychotic olanzapine causes weight gain by targeting serotonin receptor 2C.
[So] Source:J Clin Invest;127(9):3402-3406, 2017 Sep 01.
[Is] ISSN:1558-8238
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Atypical antipsychotics such as olanzapine often induce excessive weight gain and type 2 diabetes. However, the mechanisms underlying these drug-induced metabolic perturbations remain poorly understood. Here, we used an experimental model that reproduces olanzapine-induced hyperphagia and obesity in female C57BL/6 mice. We found that olanzapine treatment acutely increased food intake, impaired glucose tolerance, and altered physical activity and energy expenditure in mice. Furthermore, olanzapine-induced hyperphagia and weight gain were blunted in mice lacking the serotonin 2C receptor (HTR2C). Finally, we showed that treatment with the HTR2C-specific agonist lorcaserin suppressed olanzapine-induced hyperphagia and weight gain. Lorcaserin treatment also improved glucose tolerance in olanzapine-fed mice. Collectively, our studies suggest that olanzapine exerts some of its untoward metabolic effects via antagonism of HTR2C.
[Mh] Termos MeSH primário: Antipsicóticos/farmacologia
Benzodiazepinas/farmacologia
Diabetes Mellitus Tipo 2/tratamento farmacológico
Antagonistas da Serotonina/farmacologia
Ganho de Peso/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Antipsicóticos/efeitos adversos
Benzodiazepinas/efeitos adversos
Composição Corporal
Peso Corporal
Feminino
Glucose/química
Teste de Tolerância a Glucose
Hiperfagia/induzido quimicamente
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Receptor 5-HT2C de Serotonina/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antipsychotic Agents); 0 (Receptor, Serotonin, 5-HT2C); 0 (Serotonin Antagonists); 12794-10-4 (Benzodiazepines); IY9XDZ35W2 (Glucose); N7U69T4SZR (olanzapine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171024
[Lr] Data última revisão:
171024
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170815
[St] Status:MEDLINE


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[PMID]:28763213
[Au] Autor:Bucki A; Marcinkowska M; Sniecikowska J; Wieckowski K; Pawlowski M; Gluch-Lutwin M; Grybos A; Siwek A; Pytka K; Jastrzebska-Wiesek M; Partyka A; Wesolowska A; Mierzejewski P; Kolaczkowski M
[Ad] Endereço:Faculty of Pharmacy, Jagiellonian University Medical College , 9 Medyczna Street, 30-688 Kraków, Poland.
[Ti] Título:Novel 3-(1,2,3,6-Tetrahydropyridin-4-yl)-1H-indole-Based Multifunctional Ligands with Antipsychotic-Like, Mood-Modulating, and Procognitive Activity.
[So] Source:J Med Chem;60(17):7483-7501, 2017 Sep 14.
[Is] ISSN:1520-4804
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The most troublesome aspects of behavioral and psychological symptoms of dementia (BPSD) are nowadays addressed by antidepressant, anxiolytic, and antipsychotic drugs, often administered off-label. Considering their modest effectiveness in dementia patients, the increased risk of adverse events and cognitive decline, there is an unmet need for well-tolerated and effective therapy of BPSD. We designed and synthesized multifunctional ligands characterized in vitro as high-affinity partial agonists of D R, antagonists of 5-HT R, and blockers of SERT. Moreover, the molecules activated 5-HT R and blocked 5-HT R while having no relevant affinity for off-target M R and hERG channel. Compound 16 (N-{2-[4-(5-chloro-1H-indol-3-yl)-1,2,3,6-tetrahydropyridin-1-yl]ethyl}-3-methylbenzene-1-sulfonamide) exhibited a broad antipsychotic-, antidepressant-, and anxiolytic-like activity, not eliciting motor impairments in mice. Most importantly, 16 showed memory-enhancing properties and it ameliorated memory deficits induced by scopolamine. The molecule outperformed most important comparators in selected tests, indicating its potential in the treatment of both cognitive and noncognitive (behavioral and psychological) symptoms of dementia.
[Mh] Termos MeSH primário: Afeto/efeitos dos fármacos
Ansiolíticos/farmacologia
Antidepressivos/farmacologia
Antipsicóticos/farmacologia
Demência/psicologia
Indóis/farmacologia
Piridinas/farmacologia
[Mh] Termos MeSH secundário: Ansiolíticos/química
Antidepressivos/química
Antipsicóticos/química
Demência/complicações
Demência/metabolismo
Agonistas de Dopamina/química
Agonistas de Dopamina/farmacologia
Desenho de Drogas
Seres Humanos
Indóis/química
Ligantes
Modelos Moleculares
Piridinas/química
Receptores de Dopamina D2/agonistas
Receptores de Serotonina/metabolismo
Agonistas de Receptores 5-HT1 de Serotonina/química
Agonistas de Receptores 5-HT1 de Serotonina/farmacologia
Antagonistas da Serotonina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Anxiety Agents); 0 (Antidepressive Agents); 0 (Antipsychotic Agents); 0 (Dopamine Agonists); 0 (Indoles); 0 (Ligands); 0 (Pyridines); 0 (Receptors, Dopamine D2); 0 (Receptors, Serotonin); 0 (Serotonin 5-HT1 Receptor Agonists); 0 (Serotonin Antagonists); 0 (serotonin 6 receptor); 0 (serotonin 7 receptor)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170802
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jmedchem.7b00839


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[PMID]:28675829
[Au] Autor:Liu R; Su Y; Yang J; Wang A
[Ad] Endereço:State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
[Ti] Título:Polyprenylated acylphloroglucinols from Hypericum scabrum.
[So] Source:Phytochemistry;142:38-50, 2017 Oct.
[Is] ISSN:1873-3700
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Fourteen phloroglucinols, named hyperciumoxide A-N, and a known compound were isolated from air-dried aerial parts of Hypericum scabrum. The structures of these compounds were deduced on the basis of extensive 1D- and 2D-NMR experiments. Hepatoprotective properties against D-galactosamine-induced HL-7702 cell damage of isolated compounds were evaluated. Meanwhile, these compounds were also tested for antidepressant activity by inhibiting reuptake of tritiated serotonin ([ H]-5-HT) and Noradrenalinet ([ H]-NE) in rat brain synaptosomes.
[Mh] Termos MeSH primário: Antidepressivos/isolamento & purificação
Medicamentos de Ervas Chinesas/isolamento & purificação
Compostos Heterocíclicos de Anel em Ponte/farmacologia
Hypericum/química
Floroglucinol/isolamento & purificação
Componentes Aéreos da Planta/química
Antagonistas da Serotonina/isolamento & purificação
[Mh] Termos MeSH secundário: Animais
Antidepressivos/química
Antidepressivos/farmacologia
Encéfalo/efeitos dos fármacos
Cicloexanonas/química
Cicloexanonas/isolamento & purificação
Cicloexanonas/farmacologia
Medicamentos de Ervas Chinesas/química
Medicamentos de Ervas Chinesas/farmacologia
Células HL-60
Compostos Heterocíclicos de Anel em Ponte/química
Seres Humanos
Fígado/efeitos dos fármacos
Estrutura Molecular
Ressonância Magnética Nuclear Biomolecular
Floroglucinol/análogos & derivados
Floroglucinol/química
Floroglucinol/farmacologia
Ratos
Antagonistas da Serotonina/química
Antagonistas da Serotonina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antidepressive Agents); 0 (Cyclohexanones); 0 (Drugs, Chinese Herbal); 0 (Heterocyclic Compounds, Bridged-Ring); 0 (Serotonin Antagonists); 0 (hyperciumoxide N); 5QOR3YM052 (cyclohexanone); DHD7FFG6YS (Phloroglucinol)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170915
[Lr] Data última revisão:
170915
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170705
[St] Status:MEDLINE


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[PMID]:28626072
[Au] Autor:Seitz BM; Orer HS; Krieger-Burke T; Darios ES; Thompson JM; Fink GD; Watts SW
[Ad] Endereço:Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan; and.
[Ti] Título:5-HT causes splanchnic venodilation.
[So] Source:Am J Physiol Heart Circ Physiol;313(3):H676-H686, 2017 Sep 01.
[Is] ISSN:1522-1539
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Serotonin [5-hydroxytryptamine (5-HT)] causes relaxation of the isolated superior mesenteric vein, a splanchnic blood vessel, through activation of the 5-HT receptor. As part of studies designed to identify the mechanism(s) through which chronic (≥24 h) infusion of 5-HT lowers blood pressure, we tested the hypothesis that 5-HT causes in vitro and in vivo splanchnic venodilation that is 5-HT receptor dependent. In tissue baths for measurement of isometric contraction, the portal vein and abdominal inferior vena cava relaxed to 5-HT and the 5-HT receptor agonist 5-carboxamidotryptamine; relaxation was abolished by the 5-HT receptor antagonist SB-269970. Western blot analyses showed that the abdominal inferior vena cava and portal vein express 5-HT receptor protein. In contrast, the thoracic vena cava, outside the splanchnic circulation, did not relax to serotonergic agonists and exhibited minimal expression of the 5-HT receptor. Male Sprague-Dawley rats with chronically implanted radiotelemetry transmitters underwent repeated ultrasound imaging of abdominal vessels. After baseline imaging, minipumps containing vehicle (saline) or 5-HT (25 µg·kg ·min ) were implanted. Twenty-four hours later, venous diameters were increased in rats with 5-HT-infusion (percent increase from baseline: superior mesenteric vein, 17.5 ± 1.9; portal vein, 17.7 ± 1.8; and abdominal inferior vena cava, 46.9 ± 8.0) while arterial pressure was decreased (~13 mmHg). Measures returned to baseline after infusion termination. In a separate group of animals, treatment with SB-269970 (3 mg/kg iv) prevented the splanchnic venodilation and fall in blood pressure during 24 h of 5-HT infusion. Thus, 5-HT causes 5-HT receptor-dependent splanchnic venous dilation associated with a fall in blood pressure. This research is noteworthy because it combines and links, through the 5-HT receptor, an in vitro observation (venorelaxation) with in vivo events (venodilation and fall in blood pressure). This supports the idea that splanchnic venodilation plays a role in blood pressure regulation.
[Mh] Termos MeSH primário: Veias Mesentéricas/efeitos dos fármacos
Receptores de Serotonina/efeitos dos fármacos
Agonistas de Receptores de Serotonina/farmacologia
Serotonina/farmacologia
Circulação Esplâncnica/efeitos dos fármacos
Vasodilatação/efeitos dos fármacos
Vasodilatadores/farmacologia
[Mh] Termos MeSH secundário: Animais
Pressão Arterial/efeitos dos fármacos
Relação Dose-Resposta a Droga
Técnicas In Vitro
Infusões Intravenosas
Masculino
Veias Mesentéricas/diagnóstico por imagem
Veias Mesentéricas/metabolismo
Veia Porta/efeitos dos fármacos
Veia Porta/metabolismo
Ratos Sprague-Dawley
Receptores de Serotonina/metabolismo
Serotonina/administração & dosagem
Antagonistas da Serotonina/farmacologia
Agonistas de Receptores de Serotonina/administração & dosagem
Telemetria
Fatores de Tempo
Ultrassonografia
Vasodilatadores/administração & dosagem
Veia Cava Inferior/efeitos dos fármacos
Veia Cava Inferior/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Receptors, Serotonin); 0 (Serotonin Antagonists); 0 (Serotonin Receptor Agonists); 0 (Vasodilator Agents); 0 (serotonin 7 receptor); 333DO1RDJY (Serotonin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171005
[Lr] Data última revisão:
171005
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170620
[St] Status:MEDLINE
[do] DOI:10.1152/ajpheart.00165.2017


  10 / 14298 MEDLINE  
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[PMID]:28504917
[Au] Autor:Lalut J; Karila D; Dallemagne P; Rochais C
[Ad] Endereço:Centre d'Etudes et de Recherche sur le Médicament de Normandie, Normandie Univ, UNICAEN, CERMN, 14000 Caen, France.
[Ti] Título:Modulating 5-HT and 5-HT receptors in Alzheimer's disease treatment.
[So] Source:Future Med Chem;9(8):781-795, 2017 May.
[Is] ISSN:1756-8927
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Alzheimer's disease (AD) is the most common form of dementia affecting millions of patients worldwide which can only be treated with symptomatic drugs. Among the numbers of biological targets which are today explored in order to prevent or limit the progression of AD, the modulation of 5-HT R and 5-HT R appeared to be promising. This modulation has been proved to enhance the cognition in AD through modulation of the neurotransmitter system but could also be beneficial in order to limit the amyloid pathology. This review will describe recent advances in the understanding of this modulation as well as the medicinal chemistry of 5-HT R or 5-HT R ligands from synthesis to ongoing clinical trials.
[Mh] Termos MeSH primário: Doença de Alzheimer/tratamento farmacológico
Receptores de Serotonina/metabolismo
Antagonistas da Serotonina/farmacologia
[Mh] Termos MeSH secundário: Química Farmacêutica
Seres Humanos
Antagonistas da Serotonina/síntese química
Antagonistas da Serotonina/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Receptors, Serotonin); 0 (Serotonin Antagonists); 0 (serotonin 5 receptor); 0 (serotonin 6 receptor)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170912
[Lr] Data última revisão:
170912
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170516
[St] Status:MEDLINE
[do] DOI:10.4155/fmc-2017-0031



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