Base de dados : MEDLINE
Pesquisa : D03.383.621.644 [Categoria DeCS]
Referências encontradas : 517 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 52 ir para página                         

  1 / 517 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28277663
[Au] Autor:Tseng CC; Noordali H; Sani M; Madhani M; Grant DM; Frenneaux MP; Zanda M; Greig IR
[Ad] Endereço:Kosterlitz Centre for Therapeutics, University of Aberdeen , Foresterhill, Aberdeen, AB25 2ZD, U.K.
[Ti] Título:Development of Fluorinated Analogues of Perhexiline with Improved Pharmacokinetic Properties and Retained Efficacy.
[So] Source:J Med Chem;60(7):2780-2789, 2017 Apr 13.
[Is] ISSN:1520-4804
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We designed and synthesized perhexiline analogues that have the same therapeutic profile as the parent cardiovascular drug but lacking its metabolic liability associated with CYP2D6 metabolism. Cycloalkyl perhexiline analogues 6a-j were found to be unsuitable for further development, as they retained a pharmacokinetic profile very similar to that shown by the parent compound. Multistep synthesis of perhexiline analogues incorporating fluorine atoms onto the cyclohexyl ring(s) provided a range of different fluoroperhexiline analogues. Of these, analogues 50 (4,4-gem-difluoro) and 62 (4,4,4',4'-tetrafluoro) were highly stable and showed greatly reduced susceptibility to CYP2D6-mediated metabolism. In vitro efficacy studies demonstrated that a number of derivatives retained acceptable potency against CPT-1. Having the best balance of properties, 50 was selected for further evaluation. Like perhexiline, it was shown to be selectively concentrated in the myocardium and, using the Langendorff model, to be effective in improving both cardiac contractility and relaxation when challenged with high fat buffer.
[Mh] Termos MeSH primário: Fármacos Cardiovasculares/química
Fármacos Cardiovasculares/farmacocinética
Perexilina/análogos & derivados
Perexilina/farmacocinética
[Mh] Termos MeSH secundário: Animais
Fármacos Cardiovasculares/metabolismo
Fármacos Cardiovasculares/farmacologia
Citocromo P-450 CYP2D6/metabolismo
Halogenação
Coração/efeitos dos fármacos
Coração/fisiologia
Seres Humanos
Masculino
Camundongos Endogâmicos BALB C
Contração Miocárdica/efeitos dos fármacos
Miocárdio/metabolismo
Perexilina/metabolismo
Perexilina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cardiovascular Agents); EC 1.14.14.1 (Cytochrome P-450 CYP2D6); KU65374X44 (Perhexiline)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170424
[Lr] Data última revisão:
170424
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170310
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jmedchem.6b01592


  2 / 517 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27813339
[Au] Autor:Heggermont WA; Papageorgiou AP; Heymans S; van Bilsen M
[Ad] Endereço:Centre for Molecular and Vascular Biology, Department of Cardiovascular Research, University of Leuven, Belgium.
[Ti] Título:Metabolic support for the heart: complementary therapy for heart failure?
[So] Source:Eur J Heart Fail;18(12):1420-1429, 2016 Dec.
[Is] ISSN:1879-0844
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The failing heart has an increased metabolic demand and at the same time suffers from impaired energy efficiency, which is a detrimental combination. Therefore, therapies targeting the energy-deprived failing heart and rewiring cardiac metabolism are of great potential, but are lacking in daily clinical practice. Metabolic impairment in heart failure patients has been well characterized for patients with reduced ejection fraction, and is coming of age in patients with 'preserved' ejection fraction. Targeting cardiomyocyte metabolism in heart failure could complement current heart failure treatments that do improve cardiovascular haemodynamics, but not the energetic status of the heart. In this review, we discuss the hallmarks of normal cardiac metabolism, typical metabolic disturbances in heart failure, and past and present therapeutic targets that impact on cardiac metabolism.
[Mh] Termos MeSH primário: Insuficiência Cardíaca/metabolismo
Miocárdio/metabolismo
Miócitos Cardíacos/metabolismo
[Mh] Termos MeSH secundário: Acetil-CoA C-Aciltransferase/antagonistas & inibidores
Fármacos Cardiovasculares/uso terapêutico
Carnitina/análogos & derivados
Carnitina/uso terapêutico
Carnitina O-Palmitoiltransferase/antagonistas & inibidores
Ácido Dicloroacético/uso terapêutico
Metabolismo Energético
Inibidores Enzimáticos/uso terapêutico
Compostos de Epóxi/uso terapêutico
Ácidos Graxos/metabolismo
Glucose/metabolismo
Insuficiência Cardíaca/tratamento farmacológico
Insuficiência Cardíaca/fisiopatologia
Seres Humanos
Oxirredução
Perexilina/uso terapêutico
Ranolazina/uso terapêutico
Volume Sistólico
Trimetazidina/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Cardiovascular Agents); 0 (Enzyme Inhibitors); 0 (Epoxy Compounds); 0 (Fatty Acids); 17298-37-2 (propionylcarnitine); 9LSH52S3LQ (Dichloroacetic Acid); A6IEZ5M406 (Ranolazine); EC 2.3.1.16 (Acetyl-CoA C-Acyltransferase); EC 2.3.1.21 (Carnitine O-Palmitoyltransferase); IY9XDZ35W2 (Glucose); KU65374X44 (Perhexiline); MSB3DD2XP6 (etomoxir); N9A0A0R9S8 (Trimetazidine); S7UI8SM58A (Carnitine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161105
[St] Status:MEDLINE
[do] DOI:10.1002/ejhf.678


  3 / 517 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:27518281
[Au] Autor:Guidi A; Lalli C; Perlas E; Bolasco G; Nibbio M; Monteagudo E; Bresciani A; Ruberti G
[Ad] Endereço:National Research Council, Institute of Cell Biology and Neurobiology, Campus A. Buzzati-Traverso Monterotondo, Roma, Italy.
[Ti] Título:Discovery and Characterization of Novel Anti-schistosomal Properties of the Anti-anginal Drug, Perhexiline and Its Impact on Schistosoma mansoni Male and Female Reproductive Systems.
[So] Source:PLoS Negl Trop Dis;10(8):e0004928, 2016 Aug.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Schistosomiasis, one of the world's greatest human neglected tropical diseases, is caused by parasitic trematodes of the genus Schistosoma. A unique feature of schistosome biology is that the induction of sexual maturation as well as the maintenance of the differentiation status of female reproductive organs and egg production, necessary for both disease transmission and pathogenesis, are strictly dependent on the male. The treatment and most control initiatives of schistosomiasis rely today on the long-term application of a single drug, praziquantel (PZQ), mostly by campaigns of mass drug administration. PZQ, while very active on adult parasites, has much lower activity against juvenile worms. Monotherapy also favors the selection of drug resistance and, therefore, new drugs are urgently needed. METHODS AND FINDINGS: Following the screening of a small compound library with an ATP-based luminescent assay on Schistosoma mansoni schistosomula, we here report the identification and characterization of novel antischistosomal properties of the anti-anginal drug perhexiline maleate (PHX). By phenotypic worm survival assays and confocal microscopy studies we show that PHX, in vitro, has a marked lethal effect on all S. mansoni parasite life stages (newly transformed schistosomula, juvenile and adult worms) of the definitive host. We further demonstrate that sub-lethal doses of PHX significantly impair egg production and lipid depletion within the vitellarium of adult female worms. Moreover, we highlighted tegumental damage in adult male worms and remarkable reproductive system alterations in both female and male adult parasites. The in vivo study in S. mansoni-patent mice showed a notable variability of worm burdens in the individual experiments, with an overall minimal schistosomicidal effect upon PHX treatment. The short PHX half-life in mice, together with its very high rodent plasma proteins binding could be the cause of the modest efficacy of PHX in the schistosomiasis murine model. CONCLUSIONS/SIGNIFICANCE: Overall, our data indicate that PHX could represent a promising starting point for novel schistosomicidal drug discovery programmes.
[Mh] Termos MeSH primário: Genitália/efeitos dos fármacos
Perexilina/análogos & derivados
Schistosoma mansoni/efeitos dos fármacos
Schistosoma mansoni/ultraestrutura
Esquistossomose mansoni/tratamento farmacológico
Esquistossomicidas/farmacologia
[Mh] Termos MeSH secundário: Animais
Modelos Animais de Doenças
Resistência a Medicamentos
Feminino
Meia-Vida
Seres Humanos
Estágios do Ciclo de Vida/efeitos dos fármacos
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Perexilina/farmacologia
Praziquantel/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Schistosomicides); 6490C9U457 (Praziquantel); K7V8Y90G0H (perhexiline maleate); KU65374X44 (Perhexiline)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170614
[Lr] Data última revisão:
170614
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160813
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0004928


  4 / 517 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27455171
[Au] Autor:George CH; Mitchell AN; Preece R; Bannister ML; Yousef Z
[Ad] Endereço:a Wales Heart Research Institute, School of Medicine , Cardiff University , Cardiff , UK.
[Ti] Título:Pleiotropic mechanisms of action of perhexiline in heart failure.
[So] Source:Expert Opin Ther Pat;26(9):1049-59, 2016 Sep.
[Is] ISSN:1744-7674
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: The re-purposing of the anti-anginal drug perhexiline (PHX) has resulted in symptomatic improvements in heart failure (HF) patients. The inhibition of carnitine palmitoyltransferase-1 (CPT-1) has been proposed as the primary mechanism underlying the therapeutic benefit of PHX. This hypothesis is contentious. AREAS COVERED: We reviewed the primary literature and patent landscape of PHX from its initial development in the 1960s through to its emergence as a drug beneficial for HF. We focused on its physico-chemistry, molecular targets, tissue accumulation and clinical dosing. EXPERT OPINION: Dogma that the beneficial effects of PHX are due primarily to potent myocardial CPT-1 inhibition is not supported by the literature and all available evidence point to it being extremely unlikely that the major effects of PHX occur via this mechanism. In vivo PHX is much more likely to be an inhibitor of surface membrane ion channels and also to have effects on other components of cellular metabolism and reactive oxygen species (ROS) generation across the cardiovascular system. However, the possibility that minor effects of PHX on CPT-1 underpin disproportionately large effects on myocardial function cannot be entirely excluded, especially given the massive accumulation of the drug in heart tissue.
[Mh] Termos MeSH primário: Fármacos Cardiovasculares/farmacologia
Insuficiência Cardíaca/tratamento farmacológico
Perexilina/farmacologia
[Mh] Termos MeSH secundário: Animais
Fármacos Cardiovasculares/farmacocinética
Carnitina O-Palmitoiltransferase/antagonistas & inibidores
Desenho de Drogas
Insuficiência Cardíaca/fisiopatologia
Seres Humanos
Terapia de Alvo Molecular
Patentes como Assunto
Perexilina/farmacocinética
Espécies Reativas de Oxigênio/metabolismo
Distribuição Tecidual
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Cardiovascular Agents); 0 (Reactive Oxygen Species); EC 2.3.1.21 (Carnitine O-Palmitoyltransferase); KU65374X44 (Perhexiline)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170310
[Lr] Data última revisão:
170310
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160726
[St] Status:MEDLINE
[do] DOI:10.1080/13543776.2016.1211111


  5 / 517 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27106834
[Au] Autor:Chong CR; Sallustio B; Horowitz JD
[Ad] Endereço:Cardiology Unit, The Queen Elizabeth Hospital, 28, Woodville Road, Woodville South, SA, 5011, Australia.
[Ti] Título:Drugs that Affect Cardiac Metabolism: Focus on Perhexiline.
[So] Source:Cardiovasc Drugs Ther;30(4):399-405, 2016 Aug.
[Is] ISSN:1573-7241
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Approaches to the pharmacotherapy of angina pectoris have previously centred on the concept that a transient imbalance between myocardial oxygen "demand" and supply within the myocardium can best be addressed by reducing demand (for example, with ß-adrenoceptor antagonist) or by increasing availability of blood (via coronary vasomotor reactivity adjustment or coronary revascularization). However, this principle is potentially challenged by the emergence of cases of angina unsuitable for such therapies (for example because of concomitant severe systolic heart failure) and by the recognition that impaired myocardial energetics may precipitate angina in the absence of fixed or variable coronary obstruction (for example in hypertrophic cardiomyopathy). The past 20 years have seen the re-emergence of a class of anti-anginal agents which act primarily by improving efficiency of myocardial oxygen utilization, and thus can correct impaired energetics, simultaneously treating angina and heart failure symptoms. We review the principles underlying the safe use of such agents, beginning with the prototype drug perhexiline maleate, which despite complex pharmacokinetics and potential hepato- or neuro-toxicity has emerged as an attractive management option in many "complicated" cases of angina pectoris.
[Mh] Termos MeSH primário: Angina Pectoris/tratamento farmacológico
Fármacos Cardiovasculares/uso terapêutico
Miocárdio/metabolismo
Perexilina/análogos & derivados
[Mh] Termos MeSH secundário: Angina Pectoris/metabolismo
Animais
Fármacos Cardiovasculares/farmacologia
Ácidos Graxos/metabolismo
Glucose/metabolismo
Seres Humanos
Mitocôndrias/metabolismo
Perexilina/farmacologia
Perexilina/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Cardiovascular Agents); 0 (Fatty Acids); IY9XDZ35W2 (Glucose); K7V8Y90G0H (perhexiline maleate); KU65374X44 (Perhexiline)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:171026
[Lr] Data última revisão:
171026
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160424
[St] Status:MEDLINE
[do] DOI:10.1007/s10557-016-6664-3


  6 / 517 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27065330
[Au] Autor:Liu PP; Liu J; Jiang WQ; Carew JS; Ogasawara MA; Pelicano H; Croce CM; Estrov Z; Xu RH; Keating MJ; Huang P
[Ad] Endereço:Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
[Ti] Título:Elimination of chronic lymphocytic leukemia cells in stromal microenvironment by targeting CPT with an antiangina drug perhexiline.
[So] Source:Oncogene;35(43):5663-5673, 2016 Oct 27.
[Is] ISSN:1476-5594
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the western countries and is currently incurable due, in part, to difficulty in eliminating the leukemia cells protected by stromal microenvironment. Based on previous observations that CLL cells exhibit mitochondrial dysfunction and altered lipid metabolism and that carnitine palmitoyltransferases (CPT) have a major role in transporting fatty acid into mitochondria to support cancer cell metabolism, we tested several clinically relevant inhibitors of lipid metabolism for their ability to eliminate primary CLL cells. We discovered that perhexiline, an antiangina agent that inhibits CPT, was highly effective in killing CLL cells in stromal microenvironment at clinically achievable concentrations. These effective concentrations caused low toxicity to normal lymphocytes and normal stromal cells. Mechanistic study revealed that CLL cells expressed high levels of CPT1 and CPT2. Suppression of fatty acid transport into mitochondria by inhibiting CPT using perhexiline resulted in a depletion of cardiolipin, a key component of mitochondrial membranes, and compromised mitochondrial integrity, leading to rapid depolarization and massive CLL cell death. The therapeutic activity of perhexiline was further demonstrated in vivo using a CLL transgenic mouse model. Perhexiline significantly prolonged the overall animal survival by only four drug injections. Our study suggests that targeting CPT using an antiangina drug is able to effectively eliminate leukemia cells in vivo, and is a novel therapeutic strategy for potential clinical treatment of CLL.
[Mh] Termos MeSH primário: Carnitina O-Palmitoiltransferase/antagonistas & inibidores
Leucemia Linfocítica Crônica de Células B/metabolismo
Leucemia Linfocítica Crônica de Células B/patologia
Perexilina/farmacologia
Células Estromais/efeitos dos fármacos
Células Estromais/metabolismo
Microambiente Tumoral/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/farmacologia
Cardiolipinas/metabolismo
Carnitina O-Palmitoiltransferase/genética
Carnitina O-Palmitoiltransferase/metabolismo
Linhagem Celular
Sobrevivência Celular/efeitos dos fármacos
Modelos Animais de Doenças
Expressão Gênica
Glucose/metabolismo
Seres Humanos
Leucemia Linfocítica Crônica de Células B/tratamento farmacológico
Leucemia Linfocítica Crônica de Células B/mortalidade
Camundongos
Camundongos Knockout
Mitocôndrias/metabolismo
Membranas Mitocondriais/metabolismo
Modelos Biológicos
Consumo de Oxigênio
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Cardiolipins); EC 2.3.1.21 (Carnitine O-Palmitoyltransferase); IY9XDZ35W2 (Glucose); KU65374X44 (Perhexiline)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170930
[Lr] Data última revisão:
170930
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160412
[St] Status:MEDLINE
[do] DOI:10.1038/onc.2016.103


  7 / 517 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:26993743
[Au] Autor:Loudon BL; Noordali H; Gollop ND; Frenneaux MP; Madhani M
[Ad] Endereço:Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, UK.
[Ti] Título:Present and future pharmacotherapeutic agents in heart failure: an evolving paradigm.
[So] Source:Br J Pharmacol;173(12):1911-24, 2016 Jun.
[Is] ISSN:1476-5381
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Many conditions culminate in heart failure (HF), a multi-organ systemic syndrome with an intrinsically poor prognosis. Pharmacotherapeutic agents that correct neurohormonal dysregulation and haemodynamic instability have occupied the forefront of developments within the treatment of HF in the past. Indeed, multiple trials aimed to validate these agents in the 1980s and early 1990s, resulting in a large and robust evidence-base supporting their use clinically. An established treatment paradigm now exists for the treatment of HF with reduced ejection fraction (HFrEF), but there have been very few notable developments in recent years. HF remains a significant health concern with an increasing incidence as the population ages. We may indeed be entering the surgical era for HF treatment, but these therapies remain expensive and inaccessible to many. Newer pharmacotherapeutic agents are slowly emerging, many targeting alternative therapeutic pathways, but with mixed results. Metabolic modulation and manipulation of the nitrate/nitrite/nitric oxide pathway have shown promise and could provide the answers to fill the therapeutic gap between medical interventions and surgery, but further definitive trials are warranted. We review the significant evidence base behind the current medical treatments for HFrEF, the physiology of metabolic impairment in HF, and discuss two promising novel agents, perhexiline and nitrite.
[Mh] Termos MeSH primário: Fármacos Cardiovasculares/uso terapêutico
Insuficiência Cardíaca/tratamento farmacológico
Nitritos/uso terapêutico
Perexilina/uso terapêutico
[Mh] Termos MeSH secundário: Insuficiência Cardíaca/metabolismo
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Cardiovascular Agents); 0 (Nitrites); KU65374X44 (Perhexiline)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160320
[St] Status:MEDLINE
[do] DOI:10.1111/bph.13480


  8 / 517 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:26517851
[Au] Autor:Esposito S; Bracacel E; Nibbio M; Speziale R; Orsatti L; Veneziano M; Monteagudo E; Bonelli F
[Ad] Endereço:IRBM Science Park, Via Pontina km 30,600, 00040 Pomezia, Roma, Italy. Electronic address: s.esposito@irbm.it.
[Ti] Título:Use of 'dilute-and-shoot' liquid chromatography-high resolution mass spectrometry in preclinical research: application to a DMPK study of perhexiline in mouse plasma.
[So] Source:J Pharm Biomed Anal;118:70-80, 2016 Jan 25.
[Is] ISSN:1873-264X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:This work describes a simple, sensitive and rapid liquid chromatography-high resolution mass spectrometry method for the quantitation of perhexiline and the simultaneous detection of perhexiline metabolites in C57bl/6 mice plasma. Only 5 µL of plasma was used for analysis. Pretreatment was limited to a 100-fold dilution ('dilute-and-shoot'). The analyte was detected by high resolution mass spectrometry (Orbitrap™ technology). Three scan events were performed over the entire chromatogram. Targeted single ion monitoring with data dependent acquisition was employed for perhexiline quantitation and confirmation, while full scan was used to perform untargeted detection of perhexiline phase I and phase II circulating metabolites. The calibration curve was linear (r(2)=0.990) ranging from 0.305 ng/mL (LLOQ) to 10000 ng/mL. Matrix effect was limited to 6.1%. The method was applied to a pharmacokinetic study of perhexiline in mouse plasma and the results obtained were compared to a standard sample preparation method based on protein precipitation and liquid chromatography-tandem mass spectrometry (MRM mode) detection. The new approach provided comparable results in terms of pharmacokinetics parameters estimate with a high sensitivity, additional information on perhexiline circulating metabolites and a low consumption of biological sample. The combination of the 'dilute-and-shoot' approach together with HRMS targeted and untargeted detection represents a suitable alternative to classic bioanalytical approaches in preclinical research.
[Mh] Termos MeSH primário: Perexilina/sangue
Perexilina/farmacocinética
Espectrometria de Massas em Tandem/métodos
[Mh] Termos MeSH secundário: Animais
Cromatografia Líquida/métodos
Avaliação Pré-Clínica de Medicamentos/métodos
Feminino
Camundongos
Camundongos Endogâmicos C57BL
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
KU65374X44 (Perhexiline)
[Em] Mês de entrada:1609
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151031
[St] Status:MEDLINE


  9 / 517 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:26309031
[Au] Autor:Phuong H; Choi BY; Chong CR; Raman B; Horowitz JD
[Ad] Endereço:*Pharmacy Department; and †Cardiology and Clinical Pharmacology Departments, The Queen Elizabeth Hospital, University of Adelaide, South Australia.
[Ti] Título:Can Perhexiline Be Utilized Without Long-Term Toxicity? A Clinical Practice Audit.
[So] Source:Ther Drug Monit;38(1):73-8, 2016 Feb.
[Is] ISSN:1536-3694
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Perhexiline, originally used as a first-line prophylactic antianginal agent, is now regarded primarily as a treatment for otherwise refractory myocardial ischemia. Recent studies have also demonstrated its short-term utility in heart failure, hypertrophic cardiomyopathy, and inoperable aortic stenosis. Its benefits on myocardial energetics state are potentially counter-balanced by risk of hepatotoxicity and peripheral neuropathy during long-term treatment if drug accumulation occurs. Since perhexiline exhibits complex pharmacokinetics with wide inter-individual variability, its long-term use requires regular plasma concentration monitoring. In this study, the risk of neuro- and hepato-toxicity during long-term perhexiline therapy in relation to the intensity of therapeutic drug monitoring was investigated. Furthermore, determinants of mortality during perhexiline treatment were evaluated. METHODS: In 170 patients treated with perhexiline for a median of 50 months (interquartile range: 31-94 months), outcomes and relationship to plasma drug concentrations were documented. RESULTS: Rationale for treatment with perhexiline included myocardial ischemia in 88% and severe systolic heart failure in 38%. Plasma concentrations were within the therapeutic range of 150-600 ng/mL on 65% of assay occasions and toxic levels accounted for 8.8% of measurements. No patient developed hepatotoxicity attributable to perhexiline while 3 developed peripheral neuropathy possibly induced by treatment. Actuarial 5-year survival rate was 83% overall, and 76.3% in patients with associated systolic heart failure. CONCLUSIONS: This first audit of a large population treated long-term perhexiline demonstrates the following: (1) Although the frequency of monitoring is less than ideal, therapeutic drug monitoring effectively limits occurrence of toxic drug concentrations and virtually eliminates long-term hepato- and neuro-toxicity and (2) Mortality rates during long-term therapy, notably for patients with concomitant heart failure, are surprisingly low.
[Mh] Termos MeSH primário: Fármacos Cardiovasculares/administração & dosagem
Monitoramento de Medicamentos/métodos
Perexilina/administração & dosagem
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Fármacos Cardiovasculares/efeitos adversos
Fármacos Cardiovasculares/farmacocinética
Feminino
Seguimentos
Insuficiência Cardíaca Sistólica/tratamento farmacológico
Insuficiência Cardíaca Sistólica/mortalidade
Seres Humanos
Masculino
Isquemia Miocárdica/tratamento farmacológico
Isquemia Miocárdica/mortalidade
Perexilina/efeitos adversos
Perexilina/farmacocinética
Taxa de Sobrevida
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Cardiovascular Agents); KU65374X44 (Perhexiline)
[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:150827
[St] Status:MEDLINE
[do] DOI:10.1097/FTD.0000000000000237


  10 / 517 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:26674674
[Au] Autor:Vella S; Penna I; Longo L; Pioggia G; Garbati P; Florio T; Rossi F; Pagano A
[Ad] Endereço:Dept. of Experimental Medicine (DIMES), University of Genova, Genova, Italy.
[Ti] Título:Perhexiline maleate enhances antitumor efficacy of cisplatin in neuroblastoma by inducing over-expression of NDM29 ncRNA.
[So] Source:Sci Rep;5:18144, 2015 Dec 17.
[Is] ISSN:2045-2322
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:High Risk Neuroblastoma (HR-NB) is a pediatric cancer characterized by high malignancy and remarkable cell heterogeneity within the tumour nodules. In a recent study, we demonstrated that in vitro and in vivo over-expression of the non-coding RNA NDM29 (neuroblastoma differentiation marker 29) induces NB cell differentiation, dramatically reducing their malignancy. Among gene expression changes, differentiated phenotype induced by NDM29 is characterized by decrease of the expression of ABC transporters responsible for anticancer drug resistance. Thus, the pharmacological induction of NDM29, in principle, might represent a possible novel strategy to increase cytotoxic drug responses. In this work, we identify a small molecule able to induce the expression of NDM29 in NB cells, conferring to malignant cells increased susceptibility to cisplatin cytotoxic effects. We demonstrate that the pharmacological induction of NDM29 expression in vivo enhances the antitumoral effects of chemotherapy specifically on tumour initiating/cancer stem cells sub-population, usually refractory to therapies and responsible for tumour relapse. In summary, we suggest a novel therapeutical approach possibly useful to treat very aggressive NB cases with poor prognosis. This novel pharmacological strategy aims to promote differentiation of "stem-like" cells to render them more susceptible to the killing action of cytotoxic anticancer drugs.
[Mh] Termos MeSH primário: Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
Neuroblastoma/tratamento farmacológico
Neuroblastoma/genética
RNA não Traduzido/genética
[Mh] Termos MeSH secundário: Transportadores de Cassetes de Ligação de ATP/genética
Animais
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia
Apoptose/efeitos dos fármacos
Apoptose/genética
Linhagem Celular Tumoral
Sobrevivência Celular/efeitos dos fármacos
Sobrevivência Celular/genética
Cisplatino/administração & dosagem
Cisplatino/farmacologia
Sinergismo Farmacológico
Seres Humanos
Camundongos Endogâmicos NOD
Camundongos SCID
Neuroblastoma/patologia
Perexilina/administração & dosagem
Perexilina/análogos & derivados
Perexilina/farmacologia
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Análise de Sobrevida
Carga Tumoral/efeitos dos fármacos
Carga Tumoral/genética
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (NDM29 non-coding RNA, human); 0 (RNA, Untranslated); K7V8Y90G0H (perhexiline maleate); KU65374X44 (Perhexiline); Q20Q21Q62J (Cisplatin)
[Em] Mês de entrada:1610
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151218
[St] Status:MEDLINE
[do] DOI:10.1038/srep18144



página 1 de 52 ir para página                         
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde