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[PMID]:28458431
[Au] Autor:Ali S; Omer MO; Chaudhry MA; Ashraf M; Bukhsh A
[Ad] Endereço:Department of Pharmacology and Toxicology, University of Veterinary and Animal Sciences, Lahore, 54000, Punjab, Pakistan.
[Ti] Título:A pharmacological evidence for the presence of antihistaminic and anticholinergic activities in Roxb.
[So] Source:Indian J Pharmacol;49(1):98-101, 2017 Jan-Feb.
[Is] ISSN:1998-3751
[Cp] País de publicação:India
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: The study was designed to evaluate possible antihistaminic and anticholinergic activities of . MATERIALS AND METHODS: Effects of crude ethanolic (Ed.Eth) and effects of crude aqueous (Ed.Aq) extracts of were studied using isolated guinea pig ileum, rabbit jejunum, and rabbit trachea. Tissue responses were recorded using isotonic and isometric transducers, connected with PowerLab data acquisition system. RESULTS: A dose-dependent (0.1-0.3 mg/ml) rightward shift was demonstrated in histamine concentration-response curves. Whereas a complete relaxation of carbachol (1 µM)-induced contractions in isolated rabbit jejunum (3 mg/ml) and tracheal (10 mg/ml) preparations was observed, similar to dicyclomine at 1 and 3 µM, respectively. However, no significant difference between the effects of Ed.Eth and Ed.Aq was observed. CONCLUSION: Study provides pharmacological evidence for the presence of antihistaminic and anticholinergic activities in crude extracts of and also highlight its medicinal significance in the management of airway and gastrointestinal disorders.
[Mh] Termos MeSH primário: Antagonistas Colinérgicos/farmacologia
Equisetum/química
Antagonistas dos Receptores Histamínicos/farmacologia
Extratos Vegetais/farmacologia
[Mh] Termos MeSH secundário: Animais
Antagonistas Colinérgicos/administração & dosagem
Antagonistas Colinérgicos/isolamento & purificação
Diciclomina/administração & dosagem
Diciclomina/farmacologia
Relação Dose-Resposta a Droga
Feminino
Cobaias
Antagonistas dos Receptores Histamínicos/administração & dosagem
Íleo/efeitos dos fármacos
Íleo/metabolismo
Jejuno/efeitos dos fármacos
Jejuno/metabolismo
Masculino
Extratos Vegetais/administração & dosagem
Coelhos
Traqueia/efeitos dos fármacos
Traqueia/metabolismo
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cholinergic Antagonists); 0 (Histamine Antagonists); 0 (Plant Extracts); 4KV4X8IF6V (Dicyclomine)
[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:10.4103/0253-7613.201017


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[PMID]:28069575
[Au] Autor:Dyer O
[Ti] Título:Flawed invisible trial underpins US morning sickness drug, researchers say.
[So] Source:BMJ;356:j132, 2017 Jan 09.
[Is] ISSN:1756-1833
[Cp] País de publicação:England
[La] Idioma:eng
[Mh] Termos MeSH primário: Antieméticos/uso terapêutico
Ensaios Clínicos como Assunto/normas
Diciclomina/uso terapêutico
Doxilamina/uso terapêutico
Êmese Gravídica/tratamento farmacológico
Piridoxina/uso terapêutico
[Mh] Termos MeSH secundário: Aprovação de Drogas
Combinação de Medicamentos
Feminino
Seres Humanos
Gravidez
[Pt] Tipo de publicação:NEWS
[Nm] Nome de substância:
0 (Antiemetics); 0 (Drug Combinations); 0 (dicyclomine, doxylamine, pyridoxine drug combination); 4KV4X8IF6V (Dicyclomine); 95QB77JKPL (Doxylamine); KV2JZ1BI6Z (Pyridoxine)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170111
[St] Status:MEDLINE
[do] DOI:10.1136/bmj.j132


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[PMID]:28052111
[Au] Autor:Zhang R; Persaud N
[Ad] Endereço:Department of Family and Community Medicine, University of Toronto, Toronto, Ontario, Canada.
[Ti] Título:8-Way Randomized Controlled Trial of Doxylamine, Pyridoxine and Dicyclomine for Nausea and Vomiting during Pregnancy: Restoration of Unpublished Information.
[So] Source:PLoS One;12(1):e0167609, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: We report information about an unpublished 1970s study ("8-way" Bendectin Study) that aimed to evaluate the relative therapeutic efficacy of doxylamine, pyridoxine, and dicyclomine in the management of nausea and vomiting during pregnancy. We are publishing the trial's findings according to the restoring invisible and abandoned trials (RIAT) initiative because the trial was never published. DESIGN: Double blinded, multi-centred, randomized placebo-controlled study. SETTING: 14 clinics in the United States. PARTICIPANTS: 2308 patients in the first 12 weeks of pregnancy with complaints of nausea or vomiting were enrolled. INTERVENTIONS: Each patient was randomized to one of eight arms: placebo, doxylamine/pyridoxine/dicylcomine, doxylamine/pyridoxine, dicylomine/pyridoxine, doxylamine, dicyclomine/pyridoxine, pyridoxine and dicyclomine. Each patient was instructed to take 2 tablets at bedtime and 1 additional tablet in the afternoon or morning if needed, for 7 nights. OUTCOMES: Reported outcomes included the number of hours of nausea reported by patients, the frequency of vomiting reported by patients and the overall efficacy of medication as judged by physicians. RESULTS: Data from 1599 (69% of those randomized) participants were analyzed. Based on the available summary data of physician evaluation of symptoms and ignoring missing data and data integrity issues, the proportion of participants who were "evaluated moderate or excellent" was greater in each of the seven active treatment groups when compared with placebo (57%): doxylamine/pyridoxine/dicylcomine (14% absolute difference versus placebo; 95% CI: 4 to 24), doxylamine/pyridoxine (21; 95% CI 11 to 30), dicylomine/pyridoxine (21; 95% CI 11 to 30), doxylamine (20; 95% CI 10 to 29), dicyclomine/pyridoxine (4; 95% CI -6 to 14), pyridoxine (9; 95% CI -1 to 19) and dicyclomine (4; 95% CI -6 to 14). Based on incomplete information, the most common adverse events were apparently drowsiness and fatigue. There is a high risk of bias in these previously unpublished results given the high attrition rate in a 7 day trial, the lack of prespecified outcomes or analyses, and the exclusion of some data because of questionable data integrity. CONCLUSION: The available information about this "8-way Bendectin" trial indicates it should not be used to support the efficacy of doxylamine, pyridoxine or dicyclomine for the treatment of nausea and vomiting during pregnancy because of a high risk of bias. TRIAL REGISTRATION: Not registered.
[Mh] Termos MeSH primário: Diciclomina/uso terapêutico
Doxilamina/uso terapêutico
Náusea/complicações
Náusea/tratamento farmacológico
Complicações na Gravidez/tratamento farmacológico
Publicações
Piridoxina/uso terapêutico
Vômito/complicações
Vômito/tratamento farmacológico
[Mh] Termos MeSH secundário: Comportamento Cooperativo
Diciclomina/efeitos adversos
Doxilamina/efeitos adversos
Combinação de Medicamentos
Feminino
Seres Humanos
Médicos
Placebos
Gravidez
Viés de Publicação
Piridoxina/efeitos adversos
Relatório de Pesquisa
Risco
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Drug Combinations); 0 (Placebos); 0 (dicyclomine, doxylamine, pyridoxine drug combination); 4KV4X8IF6V (Dicyclomine); 95QB77JKPL (Doxylamine); KV2JZ1BI6Z (Pyridoxine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170809
[Lr] Data última revisão:
170809
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170105
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0167609


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[PMID]:27940145
[Au] Autor:Patricio RR; Soares JC; Oliveira MG
[Ad] Endereço:Departamento de Psicobiologia, Universidade Federal de São Paulo - UNIFESP, São Paulo, SP, Brazil.
[Ti] Título:M1 muscarinic receptors are necessary for retrieval of remote context fear memory.
[So] Source:Physiol Behav;169:202-207, 2017 Feb 01.
[Is] ISSN:1873-507X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Several studies have investigated the transition of consolidation of recent memory to remote memory in aversively motivated tasks, such as contextual fear conditioning (CFC) and inhibitory avoidance (IA). However, the mechanisms that serve the retrieval of remote memories, has not yet been fully understood. Some evidences suggest that the central cholinergic system appears be involved in the modulation of these processes. Therefore, the present study aimed to investigate the effects of a pre-test administration of dicyclomine, a high-affinity M1 muscarinic receptor antagonist, on the retrieval of remote memories in fear conditioning and IA tasks. Male Wistar rats were trained, and after 1 or 28days, the rats received dicyclomine (16 or 32mg/kg, intraperitoneally, i.p.) and were tested in CFC, tone fear conditioning (TFC) and IA tasks. At both time intervals, 32mg/kg dicyclomine induced impairment of CFC. In TFC task only the performance of the rats 28days after training was impaired. The IA task was not affected in any of the studied intervals. These findings suggest a differential contribution of muscarinic receptors on recent and remote memories retrieval revealing a more generalized role in remote memory.
[Mh] Termos MeSH primário: Aprendizagem da Esquiva/fisiologia
Condicionamento Clássico/fisiologia
Medo/fisiologia
Rememoração Mental/fisiologia
Receptor Muscarínico M1/metabolismo
[Mh] Termos MeSH secundário: Estimulação Acústica/efeitos adversos
Análise de Variância
Animais
Aprendizagem da Esquiva/efeitos dos fármacos
Condicionamento Clássico/efeitos dos fármacos
Diciclomina/farmacologia
Relação Dose-Resposta a Droga
Medo/efeitos dos fármacos
Masculino
Rememoração Mental/efeitos dos fármacos
Antagonistas Muscarínicos/farmacologia
Ratos
Ratos Wistar
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Muscarinic Antagonists); 0 (Receptor, Muscarinic M1); 4KV4X8IF6V (Dicyclomine)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170628
[Lr] Data última revisão:
170628
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161213
[St] Status:MEDLINE


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[PMID]:27606721
[Au] Autor:Mannan Baig A; Khan NA; Effendi V; Rana Z; Ahmad HR; Abbas F
[Ad] Endereço:aDepartment of Biological and Biomedical Sciences, Aga Khan University bDepartment of Surgery, Aga Khan University Hospital, Karachi, Pakistan cDepartment of Biological Sciences, Faculty of Science and Technology, Sunway University, Subang Jaya, Malaysia.
[Ti] Título:Differential receptor dependencies: expression and significance of muscarinic M1 receptors in the biology of prostate cancer.
[So] Source:Anticancer Drugs;28(1):75-87, 2017 Jan.
[Is] ISSN:1473-5741
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Recent reports on acetylcholine muscarinic receptor subtype 3 (CHRM3) have shown its growth-promoting role in prostate cancer. Additional studies report the proliferative effect of the cholinergic agonist carbachol on prostate cancer by its agonistic action on CHRM3. This study shows that the type 1 acetylcholine muscarinic receptor (CHRM1) contributes toward the proliferation and growth of prostate cancer. We used growth and cytotoxic assays, the prostate cancer microarray database and CHRM downstream pathways' homology of CHRM subtypes to uncover multiple signals leading to the growth of prostate cancer. Growth assays showed that pilocarpine stimulates the proliferation of prostate cancer. Moreover, it shows that carbachol exerts an additional agonistic action on nicotinic cholinergic receptor of prostate cancer cells that can be blocked by tubocurarine. With the use of selective CHRM1 antagonists such as pirenzepine and dicyclomine, a considerable inhibition of proliferation of prostate cancer cell lines was observed in dose ranging from 15-60 µg/ml of dicyclomine. The microarray database of prostate cancer shows a dominant expression of CHRM1 in prostate cancer compared with other cholinergic subtypes. The bioinformatics of prostate cancer and CHRM pathways show that the downstream signalling include PIP3-AKT-CaM-mediated growth in LNCaP and PC3 cells. Our study suggests that antagonism of CHRM1 may be a potential therapeutic target against prostate cancer.
[Mh] Termos MeSH primário: Neoplasias da Próstata/metabolismo
Receptor Muscarínico M1/metabolismo
[Mh] Termos MeSH secundário: Linhagem Celular Tumoral
Proliferação Celular/fisiologia
Diciclomina/farmacologia
Seres Humanos
Masculino
Pirenzepina/farmacologia
Neoplasias da Próstata/tratamento farmacológico
Neoplasias da Próstata/genética
Neoplasias da Próstata/patologia
Proteínas Proto-Oncogênicas c-akt/metabolismo
Receptor Muscarínico M1/antagonistas & inibidores
Receptor Muscarínico M1/biossíntese
Receptor Muscarínico M1/genética
Receptor Muscarínico M3/biossíntese
Receptor Muscarínico M3/genética
Receptor Muscarínico M3/metabolismo
Receptores Androgênicos/metabolismo
Transdução de Sinais
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (AR protein, human); 0 (CHRM1 protein, human); 0 (CHRM3 protein, human); 0 (Receptor, Muscarinic M1); 0 (Receptor, Muscarinic M3); 0 (Receptors, Androgen); 3G0285N20N (Pirenzepine); 4KV4X8IF6V (Dicyclomine); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171019
[Lr] Data última revisão:
171019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160909
[St] Status:MEDLINE


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[PMID]:27363232
[Au] Autor:Rosen JM; Alioto A; Saps M
[Ti] Título:Advances in Pain-Predominant Functional Gastrointestinal Disorders in the Adolescent.
[So] Source:Adolesc Med State Art Rev;27(1):34-56, 2016.
[Is] ISSN:1934-4287
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Dor Abdominal/terapia
Terapia Cognitiva
Dietoterapia
Gastroenteropatias/terapia
Antagonistas Muscarínicos/uso terapêutico
[Mh] Termos MeSH secundário: Dor Abdominal/diagnóstico
Dor Abdominal/psicologia
Adolescente
Amitriptilina/uso terapêutico
Antidepressivos Tricíclicos/uso terapêutico
Ciproeptadina/uso terapêutico
Diciclomina/uso terapêutico
Fármacos Gastrointestinais/uso terapêutico
Gastroenteropatias/diagnóstico
Gastroenteropatias/psicologia
Seres Humanos
Hiosciamina/uso terapêutico
Qualidade de Vida
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antidepressive Agents, Tricyclic); 0 (Gastrointestinal Agents); 0 (Muscarinic Antagonists); 1806D8D52K (Amitriptyline); 2YHB6175DO (Cyproheptadine); 4KV4X8IF6V (Dicyclomine); PX44XO846X (Hyoscyamine)
[Em] Mês de entrada:1607
[Cu] Atualização por classe:160701
[Lr] Data última revisão:
160701
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160702
[St] Status:MEDLINE


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[PMID]:27038970
[Au] Autor:Qubty W; Gelfand AA
[Ad] Endereço:UCSF Pediatric Headache, San Francisco, CA, USA. william.qubty@ucsf.edu.
[Ti] Título:The Link Between Infantile Colic and Migraine.
[So] Source:Curr Pain Headache Rep;20(5):31, 2016 May.
[Is] ISSN:1534-3081
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Infantile colic is a self-limiting disorder of excessive infant crying or fussiness that peaks at 6 weeks of age and typically improves by 3 months of age. The etiology of infantile colic has yet to be definitively elucidated, but there is increasing research to support its relationship to migraine. The aims of this review are to present recent research investigating the connection between infantile colic and migraine. The importance of identifying this connection is useful in reducing invasive and potentially harmful investigations and to identify age appropriate pharmacologic interventions that would be safe in this population.
[Mh] Termos MeSH primário: Cólica/tratamento farmacológico
Diciclomina/uso terapêutico
Dietoterapia
Transtornos de Enxaqueca/tratamento farmacológico
Inibidores da Bomba de Prótons/uso terapêutico
Simeticone/uso terapêutico
[Mh] Termos MeSH secundário: Cólica/complicações
Cólica/diagnóstico
Seres Humanos
Transtornos de Enxaqueca/complicações
Transtornos de Enxaqueca/diagnóstico
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Proton Pump Inhibitors); 4KV4X8IF6V (Dicyclomine); 8050-81-5 (Simethicone)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:171107
[Lr] Data última revisão:
171107
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160404
[St] Status:MEDLINE
[do] DOI:10.1007/s11916-016-0558-8


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[PMID]:26619084
[Au] Autor:Soares JC; Perfetto JG; Antonio BB; Oliveira MG
[Ad] Endereço:Department of Psychobiology, Universidade Federal de São Paulo (UNIFESP).
[Ti] Título:Effects of the M1 muscarinic antagonist dicyclomine on emotional memory retrieval.
[So] Source:Behav Neurosci;130(1):29-35, 2016 Feb.
[Is] ISSN:1939-0084
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Extensive research has shown the involvement of the central cholinergic system in the acquisition and consolidation of tasks involving conditioned fear responses, such as those observed in contextual fear conditioning (CFC), tone fear conditioning (TFC) and inhibitory avoidance (IA). However, there are few data concerning the role of this system in the memory retrieval process. Therefore, the present study aimed to compare the effects of the administration of an M1 antagonist on retrieval during these tasks. For each behavioral procedure, groups of male Wistar rats were trained. Twenty-four hr later, they were treated with different doses of dicyclomine (16, 32, or 64 mg/kg, i.p.) or with saline 30 min before the test session. The results showed that dicyclomine at doses of 16 and 32 mg/kg impaired CFC without interfering with IA performance. Moreover, only 64 mg/kg impaired TFC. These data suggest that M1 muscarinic receptors contribute to memory retrieval in CFC and TFC but are not essential for retrieval in IA.
[Mh] Termos MeSH primário: Aprendizagem da Esquiva/efeitos dos fármacos
Diciclomina/farmacologia
Emoções/efeitos dos fármacos
Rememoração Mental/efeitos dos fármacos
Antagonistas Muscarínicos/farmacologia
[Mh] Termos MeSH secundário: Análise de Variância
Animais
Condicionamento Clássico/efeitos dos fármacos
Relação Dose-Resposta a Droga
Medo/efeitos dos fármacos
Reação de Congelamento Cataléptica/efeitos dos fármacos
Masculino
Ratos
Ratos Wistar
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Muscarinic Antagonists); 4KV4X8IF6V (Dicyclomine)
[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:151201
[St] Status:MEDLINE
[do] DOI:10.1037/bne0000113


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Registro de Ensaios Clínicos
PubMed Central Texto completo
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[PMID]:25884778
[Au] Autor:Koren G; Clark S; Hankins GD; Caritis SN; Umans JG; Miodovnik M; Mattison DR; Matok I
[Ad] Endereço:From the Motherisk Program, Hospital for Sick Children and University of Toronto, Toronto, Canada. gkoren@sickkids.ca.
[Ti] Título:Maternal safety of the delayed-release doxylamine and pyridoxine combination for nausea and vomiting of pregnancy; a randomized placebo controlled trial.
[So] Source:BMC Pregnancy Childbirth;15:59, 2015 Mar 18.
[Is] ISSN:1471-2393
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Nausea and vomiting of pregnancy (NVP) is the most common medical condition in pregnancy, affecting up to 80% of expecting mothers. In April 2013 the FDA approved the delayed release combination of doxylamine succinate and -pyridoxine hydrochloride (Diclegis®) for NVP, following a phase 3 randomized trial in pregnant women. The fetal safety of this medication has been proven by numerous studies. However, because it is the only FDA-approved medication for NVP that is likely to be used by a large number of pregnant women, its maternal safety is an important public health question. The Objective is to evaluate the maternal safety of doxylamine succinate -pyridoxine hydrochloride delayed-release preparation (Diclegis® as compared to placebo. METHODS: We randomized women suffering from NVP to receive Diclegis® (n = 131) or placebo (n = 125) for 14 days at doses ranging from 2-4 tablets a day, based on a pre-specified titration protocol response to symptoms. Adverse events were collected through patient diaries, clinical examination and laboratory testing. RESULTS: Doxylamine succinate 10 mg and pyridoxine hydrochloride 10 mg use was not associated with an increased rate of any adverse event over placebo, including CNS depression, gastrointestinal or cardiovascular involvement. CONCLUSIONS: Doxylamine succinate-pyridoxine hydrochloride delayed release combination is safe and well tolerated by pregnant women when used in the recommended dose of up to 4 tablets daily in treating nausea and vomiting of pregnancy. TRIAL REGISTRATION: Clinical Trial Registration No: NCT00614445 .
[Mh] Termos MeSH primário: Diciclomina
Doxilamina
Náusea
Complicações na Gravidez/tratamento farmacológico
Piridoxina
Vômito
[Mh] Termos MeSH secundário: Adulto
Antieméticos/administração & dosagem
Antieméticos/efeitos adversos
Preparações de Ação Retardada/administração & dosagem
Preparações de Ação Retardada/efeitos adversos
Diciclomina/administração & dosagem
Diciclomina/efeitos adversos
Método Duplo-Cego
Doxilamina/administração & dosagem
Doxilamina/efeitos adversos
Combinação de Medicamentos
Monitoramento de Medicamentos/métodos
Feminino
Antagonistas dos Receptores Histamínicos H1/administração & dosagem
Antagonistas dos Receptores Histamínicos H1/efeitos adversos
Seres Humanos
Náusea/tratamento farmacológico
Náusea/etiologia
Gravidez
Piridoxina/administração & dosagem
Piridoxina/efeitos adversos
Resultado do Tratamento
Complexo Vitamínico B
Vômito/tratamento farmacológico
Vômito/etiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antiemetics); 0 (Delayed-Action Preparations); 0 (Drug Combinations); 0 (Histamine H1 Antagonists); 0 (dicyclomine, doxylamine, pyridoxine drug combination); 12001-76-2 (Vitamin B Complex); 4KV4X8IF6V (Dicyclomine); 95QB77JKPL (Doxylamine); KV2JZ1BI6Z (Pyridoxine)
[Em] Mês de entrada:1601
[Cu] Atualização por classe:161215
[Lr] Data última revisão:
161215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150418
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1186/s12884-015-0488-1


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[PMID]:25881909
[Au] Autor:Welt T; Kulic L; Hoey SE; McAfoose J; Späni C; Chadha AS; Fisher A; Nitsch RM
[Ad] Endereço:Division of Psychiatry Research, University of Zürich Campus Schlieren, Switzerland.
[Ti] Título:Acute Effects of Muscarinic M1 Receptor Modulation on AßPP Metabolism and Amyloid-ß Levels in vivo: A Microdialysis Study.
[So] Source:J Alzheimers Dis;46(4):971-82, 2015.
[Is] ISSN:1875-8908
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Indirect modulation of cholinergic activity by cholinesterase inhibition is currently a widely established symptomatic treatment for Alzheimer's disease (AD). Selective activation of certain muscarinic receptor subtypes has emerged as an alternative cholinergic-based amyloid-lowering strategy for AD, as selective muscarinic M1 receptor agonists can reduce amyloid-ß (Aß) production by shifting endoproteolytic amyloid-ß protein precursor (AßPP) processing toward non-amyloidogenic pathways. In this study, we addressed the hypothesis that acute stimulation of muscarinic M1 receptors can inhibit Aß production in awake and freely moving AßPP transgenic mice. By combining intracerebral microdialysis with retrodialysis, we determined hippocampal Aß concentrations during simultaneous pharmacological modulation of brain M1 receptor function. Infusion with a M1 receptor agonist AF102B resulted in a rapid reduction of interstitial fluid (ISF) Aß levels while treatment with the M1 antagonist dicyclomine increased ISF Aß levels reaching significance within 120 minutes of treatment. The reduction in Aß levels was associated with PKCα and ERK activation resulting in increased levels of the α-secretase ADAM17 and a shift in AßPP processing toward the non-amyloidogenic processing pathway. In contrast, treatment with the M1 receptor antagonist dicyclomine caused a decrease in levels of phosphorylated ERK that was independent of PKCα, and led to an elevation of ß-secretase levels associated with increased amyloidogenic AßPP processing. The results of this study demonstrate rapid effects of in vivo M1 receptor modulation on the ISF pool of Aß and suggest that intracerebral microdialysis with retrodialysis is a useful technical approach for monitoring acute treatment effects of muscarinic receptor modulators on AßPP/Aß metabolism.
[Mh] Termos MeSH primário: Peptídeos beta-Amiloides/metabolismo
Precursor de Proteína beta-Amiloide/metabolismo
Hipocampo/metabolismo
Microdiálise/métodos
Receptor Muscarínico M1/metabolismo
[Mh] Termos MeSH secundário: Actinas/metabolismo
Secretases da Proteína Precursora do Amiloide/metabolismo
Precursor de Proteína beta-Amiloide/genética
Animais
Ácido Aspártico Endopeptidases/metabolismo
Diciclomina/farmacologia
Relação Dose-Resposta a Droga
Feminino
Regulação da Expressão Gênica/efeitos dos fármacos
Regulação da Expressão Gênica/genética
Hipocampo/efeitos dos fármacos
Camundongos
Camundongos Transgênicos
Agonistas Muscarínicos/farmacologia
Antagonistas Muscarínicos/farmacologia
Quinuclidinas/farmacologia
Estatísticas não Paramétricas
Tiofenos/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Actins); 0 (Amyloid beta-Peptides); 0 (Amyloid beta-Protein Precursor); 0 (Muscarinic Agonists); 0 (Muscarinic Antagonists); 0 (Quinuclidines); 0 (Receptor, Muscarinic M1); 0 (Thiophenes); 4KV4X8IF6V (Dicyclomine); EC 3.4.- (Amyloid Precursor Protein Secretases); EC 3.4.23.- (Aspartic Acid Endopeptidases); EC 3.4.23.46 (Bace1 protein, mouse); K9V0CDQ56E (cevimeline)
[Em] Mês de entrada:1606
[Cu] Atualização por classe:150925
[Lr] Data última revisão:
150925
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150418
[St] Status:MEDLINE
[do] DOI:10.3233/JAD-150152



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