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[PMID]:28697173
[Au] Autor:Kuzu OF; Gowda R; Noory MA; Robertson GP
[Ad] Endereço:Department of Pharmacology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
[Ti] Título:Modulating cancer cell survival by targeting intracellular cholesterol transport.
[So] Source:Br J Cancer;117(4):513-524, 2017 Aug 08.
[Is] ISSN:1532-1827
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Demand for cholesterol is high in certain cancers making them potentially sensitive to therapeutic strategies targeting cellular cholesterol homoeostasis. A potential approach involves disruption of intracellular cholesterol transport, which occurs in Niemann-Pick disease as a result of acid sphingomyelinase (ASM) deficiency. Hence, a class of lysosomotropic compounds that were identified as functional ASM inhibitors (FIASMAs) might exhibit chemotherapeutic activity by disrupting cancer cell cholesterol homoeostasis. METHODS: Here, the chemotherapeutic utility of ASM inhibition was investigated. The effect of FIASMAs on intracellular cholesterol levels, cholesterol homoeostasis, cellular endocytosis and signalling cascades were investigated. The in vivo efficacy of ASM inhibition was demonstrated using melanoma xenografts and a nanoparticle formulation was developed to overcome dose-limiting CNS-associated side effects of certain FIASMAs. RESULTS: Functional ASM inhibitors inhibited intracellular cholesterol transport leading to disruption of autophagic flux, cellular endocytosis and receptor tyrosine kinase signalling. Consequently, major oncogenic signalling cascades on which cancer cells were reliant for survival were inhibited. Two tested ASM inhibitors, perphenazine and fluphenazine that are also clinically used as antipsychotics, were effective in inhibiting xenografted tumour growth. Nanoliposomal encapsulation of the perphenazine enhanced its chemotherapeutic efficacy while decreasing CNS-associated side effects. CONCLUSIONS: This study suggests that disruption of intracellular cholesterol transport by targeting ASM could be utilised as a potential chemotherapeutic approach for treating cancer.
[Mh] Termos MeSH primário: Antidepressivos Tricíclicos/farmacologia
Antipsicóticos/farmacologia
Colesterol/metabolismo
Melanoma/tratamento farmacológico
Melanoma/metabolismo
Perfenazina/administração & dosagem
[Mh] Termos MeSH secundário: Administração Intravenosa
Administração Oral
Animais
Antidepressivos Tricíclicos/uso terapêutico
Antipsicóticos/administração & dosagem
Autofagia/efeitos dos fármacos
Transporte Biológico/efeitos dos fármacos
Transporte Biológico/genética
Sobrevivência Celular/efeitos dos fármacos
Desipramina/farmacologia
Desipramina/uso terapêutico
Endocitose/efeitos dos fármacos
Endossomos/metabolismo
Feminino
Flupentixol/farmacologia
Flupentixol/uso terapêutico
Flufenazina/farmacologia
Flufenazina/uso terapêutico
Regulação da Expressão Gênica/efeitos dos fármacos
Técnicas de Silenciamento de Genes
Células HCT116
Homeostase/efeitos dos fármacos
Homeostase/genética
Seres Humanos
Concentração Inibidora 50
Lipossomos
Lisossomos/metabolismo
Lisossomos/ultraestrutura
Células MCF-7
Melanoma/genética
Camundongos
Nortriptilina/farmacologia
Nortriptilina/uso terapêutico
Perfenazina/farmacologia
Fosfatidilinositol 3-Quinases/metabolismo
Proteínas Proto-Oncogênicas c-akt/metabolismo
Fator de Transcrição STAT3/metabolismo
Transdução de Sinais/efeitos dos fármacos
Esfingomielina Fosfodiesterase/genética
Proteína X Associada a bcl-2/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antidepressive Agents, Tricyclic); 0 (Antipsychotic Agents); 0 (Liposomes); 0 (STAT3 Transcription Factor); 0 (bcl-2-Associated X Protein); 97C5T2UQ7J (Cholesterol); BL03SY4LXB (Nortriptyline); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); EC 3.1.4.12 (Sphingomyelin Phosphodiesterase); EC 3.1.4.12 (sphingomyelin phosphodiesterase 1, human); FA0UYH6QUO (Flupenthixol); FTA7XXY4EZ (Perphenazine); S79426A41Z (Fluphenazine); TG537D343B (Desipramine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170907
[Lr] Data última revisão:
170907
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170712
[St] Status:MEDLINE
[do] DOI:10.1038/bjc.2017.200


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[PMID]:28558910
[Au] Autor:Cieslik-Boczula K
[Ad] Endereço:Faculty of Chemistry, University of Wroclaw, F. Joliot-Curie 14, 50-383 Wroclaw, Poland. Electronic address: katarzyna.cieslik@chem.uni.wroc.pl.
[Ti] Título:The PPII-to-α-helix transition of poly-l-lysine in methanol/water solvent mixtures accompanied by fibrillar self-aggregation: An influence of fluphenazine molecules.
[So] Source:Biophys Chem;227:14-20, 2017 Aug.
[Is] ISSN:1873-4200
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Fourier-transform infrared, vibrational circular dichroism spectroscopy and transmission electron microscopy are used to follow the structural changes of pure and fluphenazine (FPh)-mixed poly-l-lysine (PLL) triggered by variations of the methanol to water ratio in solvent mixtures. FPh molecules are used as an effective psychotic drug but with a strong Parkinson's-related side effect. To answer the question whether FPh molecules can modify the fibril development, the PLL polypeptide was used as a model of α-helix- and PPII-rich fibrils. It was stated that the presence of FPh molecules did not inhibit the creation of both types of PLL fibrils with clustering features. The methanol-poor aqueous solutions promote the formation of extended polyproline II (PPII) helices; however, the methanol-rich aqueous solutions induce the development of α-helices of both pure and FPh-mixed PLL. Unpredicted and interesting features of PLL fibrillogenesis are evidenced by the formation of uncommon fibrillar aggregates, which are developed in methanol/water solvents from PLL molecules rich in either α-helix or PPII structures. Possibility of PLL molecules to form ß-sheet-, α-helix- and PPII-rich fibrils demonstrating that fibrillogenesis is a common phenomenon, and fibrillar aggregates can be based on all of the basic protein secondary structures.
[Mh] Termos MeSH primário: Flufenazina/farmacologia
Polilisina/química
Solventes/farmacologia
[Mh] Termos MeSH secundário: Antipsicóticos/farmacologia
Metanol
Peptídeos/química
Polilisina/efeitos dos fármacos
Multimerização Proteica
Estrutura Secundária de Proteína/efeitos dos fármacos
Solventes/química
Água
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antipsychotic Agents); 0 (Peptides); 0 (Solvents); 059QF0KO0R (Water); 25104-18-1 (Polylysine); 25191-13-3 (polyproline); S79426A41Z (Fluphenazine); Y4S76JWI15 (Methanol)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170623
[Lr] Data última revisão:
170623
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170601
[St] Status:MEDLINE


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[PMID]:27106023
[Au] Autor:Kreidler AM; Benz R; Barth H
[Ad] Endereço:Institute of Pharmacology and Toxicology, University of Ulm Medical Center, Albert-Einstein-Allee 11, 89081, Ulm, Germany.
[Ti] Título:Chloroquine derivatives block the translocation pores and inhibit cellular entry of Clostridium botulinum C2 toxin and Bacillus anthracis lethal toxin.
[So] Source:Arch Toxicol;91(3):1431-1445, 2017 Mar.
[Is] ISSN:1432-0738
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:The pathogenic bacteria Clostridium botulinum and Bacillus anthracis produce the binary protein toxins C2 and lethal toxin (LT), respectively. These toxins consist of a binding/transport (B ) component that delivers the separate enzyme (A) component into the cytosol of target cells where it modifies its specific substrate and causes cell death. The B components of C2 toxin and LT, C2IIa and PA , respectively, are ring-shaped heptamers that bind to their cellular receptors and form complexes with their A components C2I and lethal factor (LF), respectively. After receptor-mediated endocytosis of the toxin complexes, C2IIa and PA insert into the membranes of acidified endosomes and form trans-membrane pores through which C2I and LF translocate across endosomal membranes into the cytosol. C2IIa and PA also form channels in planar bilayer membranes, and we used this approach earlier to identify chloroquine as a potent blocker of C2IIa and PA pores. Here, a series of chloroquine derivatives was investigated to identify more efficient toxin inhibitors with less toxic side effects. Chloroquine, primaquine, quinacrine, and fluphenazine blocked C2IIa and PA pores in planar lipid bilayers and in membranes of living epithelial cells and macrophages, thereby preventing the pH-dependent membrane transport of the A components into the cytosol and protecting cells from intoxication with C2 toxin and LT. These potent inhibitors of toxin entry underline the central role of the translocation pores for cellular uptake of binary bacterial toxins and as relevant drug targets, and might be lead compounds for novel pharmacological strategies against severe enteric diseases and anthrax.
[Mh] Termos MeSH primário: Toxinas Bacterianas/farmacocinética
Toxinas Botulínicas/farmacocinética
Cloroquina/farmacologia
[Mh] Termos MeSH secundário: Antígenos de Bactérias
Transporte Biológico/efeitos dos fármacos
Membrana Celular/química
Membrana Celular/efeitos dos fármacos
Membrana Celular/metabolismo
Flufenazina/farmacologia
Células HeLa/efeitos dos fármacos
Seres Humanos
Bicamadas Lipídicas
Primaquina/farmacologia
Quinacrina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, Bacterial); 0 (Bacterial Toxins); 0 (Lipid Bilayers); 0 (anthrax toxin); 886U3H6UFF (Chloroquine); EC 3.4.24.69 (Botulinum Toxins); FPM7829VMX (botulinum toxin type C); H0C805XYDE (Quinacrine); MVR3634GX1 (Primaquine); S79426A41Z (Fluphenazine)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170306
[Lr] Data última revisão:
170306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160424
[St] Status:MEDLINE
[do] DOI:10.1007/s00204-016-1716-9


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[PMID]:27793910
[Au] Autor:Cheon JH; Lee BM; Kim HS; Yoon S
[Ad] Endereço:School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea.
[Ti] Título:Highly Halaven-resistant KBV20C Cancer Cells Can Be Sensitized by Co-treatment with Fluphenazine.
[So] Source:Anticancer Res;36(11):5867-5874, 2016 11.
[Is] ISSN:1791-7530
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:AIM: To identify conditions that induce an increase in the sensitivity of highly Halaven (HAL)-resistant cancer cells compared to sensitive cells. MATERIALS AND METHODS: We observed that drug-resistant KBV20C cells are highly resistant to HAL compared to other antimitotic drugs. The concentration required to treat KBV20C cells was almost 500-fold higher than that used to treat sensitive parent KB cells. In order to increase sensitization, HAL-treated KBV20C cells were co-treated with the repositioned drug, fluphenazine (FLU). RESULTS: HAL and FLU co-treatment inhibited the growth and increased apoptosis via G arrest in HAL-treated KBV20C cancer cells. Sensitization by HAL-FLU affected retinoblastoma protein (pRB), pHistone H3 and pH2AX protein levels. FLU could also inhibit p-glycoprotein (P-gp) activity in HA-resistant KBV20C cells. These observations suggest that the mechanisms underlying FLU-HAL sensitization in resistant KBV20C cells involve both apoptosis and P-gp inhibition. Furthermore, both thioridazine (THIO) and mefloquine (MEF), but not azathioprine (AZA), sensitized HAL-treated KBV20C cells. CONCLUSION: These findings provide important information regarding the sensitization of HAL-resistant cells and indicate that FLU, THIO and MEF may have similar sensitization effects in highly HAL-resistant cells.
[Mh] Termos MeSH primário: Flufenazina/farmacologia
Furanos/farmacologia
Cetonas/farmacologia
[Mh] Termos MeSH secundário: Linhagem Celular Tumoral
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Furans); 0 (Ketones); LR24G6354G (eribulin); S79426A41Z (Fluphenazine)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170131
[Lr] Data última revisão:
170131
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161030
[St] Status:MEDLINE


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[PMID]:27708101
[Au] Autor:Perry CJ; Baciadonna L; Chittka L
[Ad] Endereço:Department of Biological and Experimental Psychology, School of Biological and Chemical Sciences, Queen Mary University of London, London E1 4NS, UK. clint.perry@qmul.ac.uk.
[Ti] Título:Unexpected rewards induce dopamine-dependent positive emotion-like state changes in bumblebees.
[So] Source:Science;353(6307):1529-1531, 2016 09 30.
[Is] ISSN:1095-9203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Whether invertebrates exhibit positive emotion-like states and what mechanisms underlie such states remain poorly understood. We demonstrate that bumblebees exhibit dopamine-dependent positive emotion-like states across behavioral contexts. After training with one rewarding and one unrewarding cue, bees that received pretest sucrose responded in a positive manner toward ambiguous cues. In a second experiment, pretest consumption of sucrose solution resulted in a shorter time to reinitiate foraging after a simulated predator attack. These behavioral changes were abolished with topical application of the dopamine antagonist fluphenazine. Further experiments established that pretest sucrose does not simply cause bees to become more exploratory. Our findings present a new opportunity for understanding the fundamental neural elements of emotions and may alter the view of how emotion states affect decision-making in animals.
[Mh] Termos MeSH primário: Abelhas/fisiologia
Comportamento Animal/fisiologia
Tomada de Decisões/fisiologia
Dopamina/fisiologia
Felicidade
[Mh] Termos MeSH secundário: Animais
Abelhas/efeitos dos fármacos
Abelhas/metabolismo
Comportamento Animal/efeitos dos fármacos
Sinais (Psicologia)
Tomada de Decisões/efeitos dos fármacos
Antagonistas de Dopamina/farmacologia
Flufenazina/farmacologia
Recompensa
Sacarose
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Dopamine Antagonists); 57-50-1 (Sucrose); S79426A41Z (Fluphenazine); VTD58H1Z2X (Dopamine)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170404
[Lr] Data última revisão:
170404
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161007
[St] Status:MEDLINE


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[PMID]:27370402
[Au] Autor:Sampford JR; Sampson S; Li BG; Zhao S; Xia J; Furtado VA
[Ad] Endereço:Crisis and Access Service, Bootham Park Hospital, York, UK.
[Ti] Título:Fluphenazine (oral) versus atypical antipsychotics for schizophrenia.
[So] Source:Cochrane Database Syst Rev;7:CD010832, 2016 Jul 02.
[Is] ISSN:1469-493X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Fluphenazine is a typical antipsychotic drug from the phenothiazine group of antipsychotics. It has been commonly used in the treatment of schizophrenia, however, with the advent of atypical antipsychotic medications, use has declined over the years. OBJECTIVES: To measure the outcomes (both beneficial and harmful) of the clinical effectiveness, safety and cost-effectiveness of oral fluphenazine versus atypical antipsychotics for schizophrenia. SEARCH METHODS: We searched the Cochrane Central Register of Studies (25 April 2013). For the economic search, we searched the Cochrane Schizophrenia Group Health Economic Database (CSzGHED) on 31 January 2014 SELECTION CRITERIA: All randomised controlled trials (RCTs) comparing fluphenazine (oral) with any other oral atypical antipsychotics. DATA COLLECTION AND ANALYSIS: Review authors worked independently to inspect citations and assess the quality of the studies and to extract data. For homogeneous dichotomous data we calculated the risk ratio (RR) and 95% confidence interval (CI), and calculated the mean differences (MDs) for continuous data. We assessed risk of bias for included studies and used GRADE (Grading of Recommendations Assessment, Development and Evaluation) to rate the quality of the evidence. MAIN RESULTS: Four studies randomising a total of 202 people with schizophrenia are included. Oral fluphenazine was compared with oral amisulpride, risperidone, quetiapine and olanzapine.Comparing oral fluphenazine with amisulpride, there was no difference between groups for mental state using the Brief Psychiatric Rating Scale (BPRS) (1 RCT, n = 57, MD 5.10 95% CI -2.35 to 12.55, very low-quality evidence), nor was there any difference in numbers leaving the study early for any reason (2 RCTs, n = 98, RR 1.19 95% CI 0.63 to 2.28, very low-quality evidence). More people required concomitant anticholinergic medication in the fluphenazine group compared to amisulpride (1 RCT, n = 36, RR 7.82 95% CI 1.07 to 57.26, very low-quality evidence). No data were reported for important outcomes including relapse, changes in life skills, quality of life or cost-effectiveness.Comparing oral fluphenazine with risperidone, data showed no difference between groups for 'clinically important response' (1 RCT, n = 26, RR 0.67 95% CI 0.13 to 3.35, very low-quality evidence) nor leaving the study early due to inefficacy (1 RCT, n = 25, RR 1.08 95% CI 0.08 to 15.46, very low-quality evidence). No data were reported data for relapse; change in life skills; quality of life; extrapyramidal adverse effects; or cost-effectiveness.Once again there was no difference when oral fluphenazine was compared with quetiapine for clinically important response (1 RCT, n = 25, RR 0.62 95% CI 0.12 to 3.07, very low-quality evidence), nor leaving the study early for any reason (1 RCT, n = 25, RR 0.46 95% CI 0.05 to 4.46, very low-quality evidence). No data were reported for relapse; clinically important change in life skills; quality of life; extrapyramidal adverse effects; or cost-effectiveness.Compared to olanzapine, fluphenazine showed no superiority for clinically important response (1 RCT, n = 60, RR 1.33 95% CI 0.86 to 2.07, very low-quality evidence), in incidence of akathisia (1 RCT, n = 60, RR 3.00 95% CI 0.90 to 10.01, very low-quality evidence) or in people leaving the study early (1 RCT, n = 60, RR 3.00 95% CI 0.33 to 27.23, very low-quality evidence). No data were reported for relapse; change in life skills; quality of life; or cost-effectiveness. AUTHORS' CONCLUSIONS: Measures of clinical response and mental state do not highlight differences between fluphenazine and amisulpride, risperidone, quetiapine or olanzapine. Largely measures of adverse effects are also unconvincing for substantive differences between fluphenazine and the newer drugs. All included trials carry a substantial risk of bias regarding reporting of adverse effects and this bias would have favoured the newer drugs. The four small short included studies do not provide much clear information about the relative merits or disadvantages of oral fluphenazine compared with newer atypical antipsychotics.
[Mh] Termos MeSH primário: Antipsicóticos/uso terapêutico
Flufenazina/uso terapêutico
Esquizofrenia/tratamento farmacológico
[Mh] Termos MeSH secundário: Administração Oral
Antipsicóticos/efeitos adversos
Benzodiazepinas/efeitos adversos
Benzodiazepinas/uso terapêutico
Flufenazina/efeitos adversos
Seres Humanos
Fumarato de Quetiapina/efeitos adversos
Fumarato de Quetiapina/uso terapêutico
Ensaios Clínicos Controlados Aleatórios como Assunto
Risperidona/efeitos adversos
Risperidona/uso terapêutico
Sulpirida/efeitos adversos
Sulpirida/análogos & derivados
Sulpirida/uso terapêutico
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Nm] Nome de substância:
0 (Antipsychotic Agents); 12794-10-4 (Benzodiazepines); 2S3PL1B6UJ (Quetiapine Fumarate); 7MNE9M8287 (Sulpiride); AA0G3TW31W (sultopride); L6UH7ZF8HC (Risperidone); N7U69T4SZR (olanzapine); S79426A41Z (Fluphenazine)
[Em] Mês de entrada:1609
[Cu] Atualização por classe:161126
[Lr] Data última revisão:
161126
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160703
[St] Status:MEDLINE
[do] DOI:10.1002/14651858.CD010832.pub2


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[PMID]:27094507
[Au] Autor:Turinawe EB
[Ad] Endereço:University of Amsterdam, Amsterdam. tbenoni@gmail.com.
[Ti] Título:'Those were taken away and given money': power and reward expectations' influence in the selection of village health teams in rural Uganda.
[So] Source:Rural Remote Health;16(2):3856, 2016 Apr-Jun.
[Is] ISSN:1445-6354
[Cp] País de publicação:Australia
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: With the renewed call for community participation in health interventions after the Alma Ata Declaration, interest has been raised in volunteer community health workers (CHWs) acting as representatives of local communities. The present study interrogates the dynamic interface between local communities and the government in the selection of CHW volunteers in a rural community. METHODS: Data were collected through participant observation of community events, 35 in-depth interviews, 20 focus groups and 15 informal conversations. A review of documents about Luwero district was also an important source of data. RESULTS: Ambiguous national guidelines and poor supervision of the selection process enabled the powerful community leaders to influence the selection of village health teams (VHTs). Intended to achieve community involvement, the selection process produced a disconnect in the local community where many members saw the selected VHTs as having been 'taken away'. CONCLUSIONS: Community involvement in the selection of VHTs took a form that, instead of empowering the local community, reinforced the responsibility of those in power and thus maintained the asymmetrical status quo.
[Mh] Termos MeSH primário: Agentes Comunitários de Saúde/organização & administração
Órgãos Governamentais/organização & administração
Política
Serviços de Saúde Rural/organização & administração
Voluntários
[Mh] Termos MeSH secundário: Participação da Comunidade
Combinação de Medicamentos
Governo Federal
Flufenazina
Seres Humanos
Governo Local
Nortriptilina
População Rural
Uganda
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Drug Combinations); 66555-51-9 (Motival); BL03SY4LXB (Nortriptyline); S79426A41Z (Fluphenazine)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170117
[Lr] Data última revisão:
170117
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160421
[St] Status:MEDLINE


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[PMID]:26732278
[Au] Autor:Schaffer LF; de Freitas CM; Chiapinotto Ceretta AP; Peroza LR; de Moraes Reis E; Krum BN; Busanello A; Boligon AA; Sudati JH; Fachinetto R; Wagner C
[Ad] Endereço:Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Maria, Santa Maria, RS, 97105-900, Brazil.
[Ti] Título:Harpagophytum Procumbens Ethyl Acetate Fraction Reduces Fluphenazine-Induced Vacuous Chewing Movements and Oxidative Stress in Rat Brain.
[So] Source:Neurochem Res;41(5):1170-84, 2016 May.
[Is] ISSN:1573-6903
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Long-term treatment with fluphenazine is associated with manifestation of extrapyramidal side effects, such as tardive dyskinesia. The molecular mechanisms related to the pathophysiology of TD remain unclear, and several hypotheses, including a role for oxidative stress, have been proposed. Harpagophytum procumbens is an herbal medicine used mainly due to anti-inflammatory effects, but it also exhibits antioxidant effects. We investigated the effect of ethyl acetate fraction of H. procumbens (EAF HP) in fluphenazine-induced orofacial dyskinesia by evaluating behavioral parameters at different times (vacuous chewing movements (VCM's) and locomotor and exploratory activity), biochemical serological analyses, and biochemical markers of oxidative stress of the liver, kidney, cortex, and striatum. Chronic administration of fluphenazine (25 mg/kg, intramuscular (i.m) significantly increased the VCMs at all analyzed times (2, 7, 14, and 21 days), and this was inhibited by EAF HP (especially at a dose of 30 mg/kg). Fluphenazine decreased locomotion and exploratory activity, and EAF HP did not improve this decrease. Fluphenazine induced oxidative damage, as identified by changes in catalase activity and ROS levels in the cortex and striatum, which was reduced by EAF HP, especially in the striatum. In the cortex, EAF HP was protective against fluphenazine-induced changes in catalase activity but not against the increase in ROS level. Furthermore, EAF HP was shown to be safe, since affected serum biochemical parameters or parameters of oxidative stress in the liver and kidney. These findings suggest that the H. procumbens is a promising therapeutic agent for the treatment of involuntary oral movements.
[Mh] Termos MeSH primário: Acetatos/química
Antioxidantes/farmacologia
Antipsicóticos/toxicidade
Encéfalo/efeitos dos fármacos
Flufenazina/toxicidade
Harpagophytum/química
Mastigação/efeitos dos fármacos
Estresse Oxidativo/efeitos dos fármacos
Extratos Vegetais/farmacologia
Discinesia Tardia/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Antioxidantes/uso terapêutico
Encéfalo/metabolismo
Comportamento Exploratório/efeitos dos fármacos
Depuradores de Radicais Livres/farmacologia
Depuradores de Radicais Livres/uso terapêutico
Masculino
Atividade Motora/efeitos dos fármacos
Extratos Vegetais/uso terapêutico
Ratos Wistar
Solventes
Discinesia Tardia/induzido quimicamente
Discinesia Tardia/metabolismo
Discinesia Tardia/psicologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Acetates); 0 (Antioxidants); 0 (Antipsychotic Agents); 0 (Free Radical Scavengers); 0 (Plant Extracts); 0 (Solvents); 76845O8NMZ (ethyl acetate); S79426A41Z (Fluphenazine)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160107
[St] Status:MEDLINE
[do] DOI:10.1007/s11064-015-1811-y


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[PMID]:26660173
[Au] Autor:Slawson MH; Johnson-Davis KL
[Ad] Endereço:ARUP Institute for Clinical and Experimental Pathology, 500 Chipeta Way, 209-D02, Salt Lake City, UT, 84108, USA. matthew.slawson@aruplab.com.
[Ti] Título:Quantitation of Haloperidol, Fluphenazine, Perphenazine, and Thiothixene in Serum or Plasma Using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS).
[So] Source:Methods Mol Biol;1383:49-57, 2016.
[Is] ISSN:1940-6029
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Haloperidol, fluphenazine, perphenazine, and thiothixene are "typical" antipsychotic drugs that are used in the treatment of schizophrenia and other psychiatric disorders. The monitoring of the use of these drugs has applications in therapeutic drug monitoring and overdose situations. LC-MS/MS is used to analyze plasma/serum extracts with deuterated analog of imipramine as the internal standard to ensure accurate quantitation and control for any potential matrix effects. Positive ion electrospray is used to introduce the analytes into the mass spectrometer. Selected reaction monitoring of two product ions for each analyte allows for the calculation of ion ratios which ensures correct identification of each analyte, while a matrix-matched calibration curve is used for quantitation.
[Mh] Termos MeSH primário: Antipsicóticos/sangue
Flufenazina/sangue
Haloperidol/sangue
Perfenazina/sangue
Espectrometria de Massas em Tandem/métodos
Tiotixeno/sangue
[Mh] Termos MeSH secundário: Cromatografia Líquida de Alta Pressão/métodos
Monitoramento de Medicamentos/métodos
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antipsychotic Agents); 7318FJ13YJ (Thiothixene); FTA7XXY4EZ (Perphenazine); J6292F8L3D (Haloperidol); S79426A41Z (Fluphenazine)
[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:151215
[St] Status:MEDLINE
[do] DOI:10.1007/978-1-4939-3252-8_6


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[PMID]:26491959
[Au] Autor:Wagman JD; Wolfe BA; Schook MW
[Ad] Endereço:Cleveland Metroparks Zoo, Conservation and Science, Cleveland, Ohio.
[Ti] Título:The effect of fluphenazine decanoate on glucocorticoid production, reproductive cyclicity, and the behavioral stress response in the Persian onager (Equus hemionus onager).
[So] Source:Zoo Biol;34(6):525-34, 2015 Nov.
[Is] ISSN:1098-2361
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Artificial insemination, performed to maximize genetic diversity in populations of zoo-housed animals, requires intensive management and has been associated with low success rates in fractious species. In these species, stressors, such as frequent handling, may impact fertility. Long-acting neuroleptic pharmaceuticals (LANs) can attenuate the stress response to handling, but may also disrupt ovulation in some species, compromising their use for artificial insemination. Therefore, the goal of this study was to determine whether LANs may be used to mitigate stress during reproductive management in wild equids without inhibiting ovulation. Six female Persian onagers (Equus hemionus onager) were treated with fluphenazine decanoate (FD; 0.1 mg/kg IM) or saline control in a random crossover design study. Urinary cortisol, progesterone, estrogen metabolites and behavior were monitored, and follicular dynamics were examined using ultrasonography until ovulation. Onagers demonstrated significantly lower cortisol concentrations (P = 0.03) when treated with FD (6.61 ± 3.26 ng/mg creatinine) compared to saline (9.73 ± 3.19 ng/mg creatinine). Overall, there were no differences in peak estrogen (P = 0.51) or progesterone (P = 0.38) concentrations between the two groups, and all animals ovulated within the expected time frame following FD treatment. However, some onagers exhibited only minor reductions in cortisol secretion and one treated female demonstrated a suppressed luteal progesterone peak, indicating a possible reproductive cost to FD administration. While FD may be useful for highly fractious equids for which the stress of handling delays or inhibits ovulation, these results warrant further investigation of dosing.
[Mh] Termos MeSH primário: Animais de Zoológico/fisiologia
Equidae/fisiologia
Ciclo Estral/efeitos dos fármacos
Flufenazina/análogos & derivados
Estresse Fisiológico/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Antipsicóticos/farmacologia
Estudos Cross-Over
Feminino
Flufenazina/farmacologia
Glucocorticoides/biossíntese
Hidrocortisona/urina
Folículo Ovariano
Progesterona/urina
Distribuição Aleatória
Reprodução/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antipsychotic Agents); 0 (Glucocorticoids); 4G7DS2Q64Y (Progesterone); FMU62K1L3C (fluphenazine depot); S79426A41Z (Fluphenazine); WI4X0X7BPJ (Hydrocortisone)
[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:151023
[St] Status:MEDLINE
[do] DOI:10.1002/zoo.21250



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