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[PMID]:28257284
[Au] Autor:Sreter KB; Barisic B; Popovic-Grle S
[Ti] Título:Pharmacogenomics and tailored polypharmacy: an 80-year-old lady with rosuvastatin-associated rhabdomyolysis and maprotiline-related Ogilvie's syndrome
.
[So] Source:Int J Clin Pharmacol Ther;55(5):442-448, 2017 May.
[Is] ISSN:0946-1965
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:What is known and objectives: Multiple adverse drug reactions (ADRs) are expected, and thus should be prevented in the elderly comorbid patient on polypharmacy. Rosuvastatin is commonly prescribed for the treatment and prevention of atherosclerotic diseases, and in rare cases, is associated with rhabdomyolysis. Maprotiline is a tetracyclic antidepressant, infrequently used in the United States, but seemingly more broadly in European countries. Acute colonic pseudo-obstruction (Ogilvie's syndrome) caused by maprotiline has thus far, to our knowledge, not yet been described in the literature. CASE SUMMARY: We present a unique case of synchronous rhabdomyolysis and Ogilvie's syndrome in an 80-year-old lung cancer survivor following a recent ischemic stroke for which she was prescribed clopidogrel and rosuvastatin for secondary prevention, and maprotiline for post-stroke, new-onset insomnia and anxiety. The ADRs resolved on removal of the offending agents and initiation of conservative treatment. Retrospective pharmacogenetic testing of the patient's drug-metabolizing enzymes and transporters was performed to guide further management and prevent future potential drug interactions and ADRs. What is novel and conclusions: This is an interesting, albeit unfortunate, complex case that depicts the risk of rare adverse effects to medications and their potential relationship to pharmacogenetics. The impact of anticholinergic side effects of antidepressants on gastrointestinal motility, risk of myopathies with statins, increased susceptibility to ADRs caused by drug-drug interactions, and the utility of pharmacogenomic testing are discussed. The question whether commercially available pharmacogenomic tools are relevant for everyday use to direct patient care and reduce harmful drug-drug interactions is addressed and warrants further research.
.
[Mh] Termos MeSH primário: Antidepressivos de Segunda Geração/efeitos adversos
Pseudo-Obstrução do Colo/induzido quimicamente
Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos
Maprotilina/efeitos adversos
Variantes Farmacogenômicos
Rabdomiólise/induzido quimicamente
Rosuvastatina Cálcica/efeitos adversos
[Mh] Termos MeSH secundário: Idoso de 80 Anos ou mais
Antidepressivos de Segunda Geração/farmacocinética
Pseudo-Obstrução do Colo/diagnóstico
Pseudo-Obstrução do Colo/genética
Sistema Enzimático do Citocromo P-450/genética
Sistema Enzimático do Citocromo P-450/metabolismo
Interações Medicamentosas
Feminino
Predisposição Genética para Doença
Seres Humanos
Inibidores de Hidroximetilglutaril-CoA Redutases/farmacocinética
Maprotilina/farmacocinética
Farmacogenética
Testes Farmacogenômicos
Fenótipo
Polimedicação
Rabdomiólise/diagnóstico
Rabdomiólise/genética
Fatores de Risco
Rosuvastatina Cálcica/farmacocinética
Membro 1b1 da Família de Transportadores de Ânion Orgânico Carreador de Soluto/genética
Membro 1b1 da Família de Transportadores de Ânion Orgânico Carreador de Soluto/metabolismo
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antidepressive Agents, Second-Generation); 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors); 0 (SLCO1B1 protein, human); 0 (Solute Carrier Organic Anion Transporter Family Member 1b1); 2U1W68TROF (Maprotiline); 83MVU38M7Q (Rosuvastatin Calcium); 9035-51-2 (Cytochrome P-450 Enzyme System)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171103
[Lr] Data última revisão:
171103
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170304
[St] Status:MEDLINE
[do] DOI:10.5414/CP202784


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[PMID]:28106668
[Au] Autor:Krügel U; Straub I; Beckmann H; Schaefer M
[Ad] Endereço:aRudolf-Boehm-Institut für Pharmakologie und Toxikologie, Universität Leipzig, Leipzig, Germany bCarl-Ludwig-Institut für Physiologie, Universität Leipzig, Leipzig, Germany.
[Ti] Título:Primidone inhibits TRPM3 and attenuates thermal nociception in vivo.
[So] Source:Pain;158(5):856-867, 2017 May.
[Is] ISSN:1872-6623
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The melastatin-related transient receptor potential (TRP) channel TRPM3 is a nonselective cation channel expressed in nociceptive neurons and activated by heat. Because TRPM3-deficient mice show inflammatory thermal hyperalgesia, pharmacological inhibition of TRPM3 may exert antinociceptive properties. Fluorometric Ca influx assays and a compound library containing approved or clinically tested drugs were used to identify TRPM3 inhibitors. Biophysical properties of channel inhibition were assessed using electrophysiological methods. The nonsteroidal anti-inflammatory drug diclofenac, the tetracyclic antidepressant maprotiline, and the anticonvulsant primidone were identified as highly efficient TRPM3 blockers with half-maximal inhibition at 0.6 to 6 µM and marked specificity for TRPM3. Most prominently, primidone was biologically active to suppress TRPM3 activation by pregnenolone sulfate (PregS) and heat at concentrations markedly lower than plasma concentrations commonly used in antiepileptic therapy. Primidone blocked PregS-induced Cai influx through TRPM3 by allosteric modulation and reversibly inhibited atypical inwardly rectifying TRPM3 currents induced by coapplication of PregS and clotrimazole. In vivo, analgesic effects of low doses of primidone were demonstrated in mice, applying PregS- and heat-induced pain models, including inflammatory hyperalgesia. Thus, applying the approved drug at concentrations that are lower than those needed to induce anticonvulsive effects offers a shortcut for studying physiological and pathophysiological roles of TRPM3 in vivo.
[Mh] Termos MeSH primário: Analgésicos/uso terapêutico
Hiperalgesia/tratamento farmacológico
Dor/fisiopatologia
Pregnenolona/toxicidade
Primidona/uso terapêutico
Canais de Cátion TRPM/metabolismo
[Mh] Termos MeSH secundário: Inibidores da Captação Adrenérgica/farmacologia
Inibidores da Captação Adrenérgica/uso terapêutico
Analgésicos/farmacologia
Animais
Anti-Inflamatórios não Esteroides/farmacologia
Anti-Inflamatórios não Esteroides/uso terapêutico
Cálcio/metabolismo
Diclofenaco/farmacologia
Modelos Animais de Doenças
Relação Dose-Resposta a Droga
Gânglios Espinais/citologia
Células HEK293
Seres Humanos
Hiperalgesia/etiologia
Masculino
Maprotilina/farmacologia
Maprotilina/uso terapêutico
Potenciais da Membrana/efeitos dos fármacos
Camundongos
Camundongos Endogâmicos C57BL
Neurônios/efeitos dos fármacos
Dor/induzido quimicamente
Limiar da Dor/efeitos dos fármacos
Técnicas de Patch-Clamp
Primidona/química
Primidona/farmacologia
Ratos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adrenergic Uptake Inhibitors); 0 (Analgesics); 0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (TRPM Cation Channels); 0 (TRPM3 protein, mouse); 13AFD7670Q (Primidone); 144O8QL0L1 (Diclofenac); 2U1W68TROF (Maprotiline); 73R90F7MQ8 (Pregnenolone); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170428
[Lr] Data última revisão:
170428
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170121
[St] Status:MEDLINE
[do] DOI:10.1097/j.pain.0000000000000846


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[PMID]:27789386
[Au] Autor:Chew WS; Shalini SM; Torta F; Wenk MR; Stohler C; Yeo JF; Herr DR; Ong WY
[Ad] Endereço:Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119260, Singapore.
[Ti] Título:Role of prefrontal cortical calcium-independent phospholipase A in antinociceptive effect of the norepinephrine reuptake inhibitor antidepresssant maprotiline.
[So] Source:Neuroscience;340:91-100, 2017 Jan 06.
[Is] ISSN:1873-7544
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The prefrontal cortex is essential for executive functions such as decision-making and planning. There is also accumulating evidence that it is important for the modulation of pain. In this study, we investigated a possible role of prefrontal cortical calcium-independent phospholipase A (iPLA ) in antinociception induced by the norepinephrine reuptake inhibitor (NRI) and tetracyclic (tricyclic) antidepressant, maprotiline. Intraperitoneal injections of maprotiline increased iPLA mRNA and protein expression in the prefrontal cortex. This treatment also reduced grooming responses to von-Frey hair stimulation of the face after facial carrageenan injection, indicating decreased sensitivity to pain. The antinociceptive effect of maprotiline was abrogated by iPLA antisense oligonucleotide injection to the prefrontal cortex, indicating a role of this enzyme in antinociception. In contrast, injection of iPLA antisense oligonucleotide to the somatosensory cortex did not reduce the antinociceptive effect of maprotiline. Lipidomic analysis of the prefrontal cortex showed decrease in phosphatidylcholine species, but increase in lysophosphatidylcholine species, indicating increased PLA2 activity, and release of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) after maprotiline treatment. Differences in sphingomyelin/ceramide were also detected. These changes were not observed in maprotiline-treated mice that received iPLA antisense oligonucleotide to the prefrontal cortex. Metabolites of DHA and EPA may help to strengthen a known supraspinal antinociceptive pathway from the prefrontal cortex to the periaqueductal gray. Together, results indicate a role of prefrontal cortical iPLA and its enzymatic products in the antinociceptive effect of maprotiline.
[Mh] Termos MeSH primário: Analgésicos/farmacologia
Dor Facial/tratamento farmacológico
Fosfolipases A2 do Grupo VI/metabolismo
Maprotilina/farmacologia
Córtex Pré-Frontal/efeitos dos fármacos
[Mh] Termos MeSH secundário: Inibidores da Captação Adrenérgica/farmacologia
Animais
Antidepressivos de Segunda Geração/farmacologia
Carragenina
Modelos Animais de Doenças
Ácidos Docosa-Hexaenoicos/metabolismo
Ácido Eicosapentaenoico/metabolismo
Dor Facial/imunologia
Fosfolipases A2 do Grupo VI/antagonistas & inibidores
Fosfolipases A2 do Grupo VI/genética
Masculino
Camundongos Endogâmicos C57BL
Limiar da Dor/efeitos dos fármacos
Limiar da Dor/fisiologia
Córtex Pré-Frontal/imunologia
RNA Mensageiro/metabolismo
Córtex Somatossensorial/efeitos dos fármacos
Córtex Somatossensorial/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adrenergic Uptake Inhibitors); 0 (Analgesics); 0 (Antidepressive Agents, Second-Generation); 0 (RNA, Messenger); 25167-62-8 (Docosahexaenoic Acids); 2U1W68TROF (Maprotiline); 9000-07-1 (Carrageenan); AAN7QOV9EA (Eicosapentaenoic Acid); EC 3.1.1.4 (Group VI Phospholipases A2); EC 3.1.1.4 (Pla2g6 protein, mouse)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171106
[Lr] Data última revisão:
171106
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161030
[St] Status:MEDLINE


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[PMID]:26742028
[Au] Autor:Karama U; Sultan MA; Almansour AI; El-Taher KE
[Ad] Endereço:Chemistry Department, College of Science, King Saud University, P. O. Box 2455 Riyadh 11451, Saudi Arabia. Karama@ksu.edu.sa.
[Ti] Título:Synthesis of Chlorinated Tetracyclic Compounds and Testing for Their Potential Antidepressant Effect in Mice.
[So] Source:Molecules;21(1):61, 2016 Jan 05.
[Is] ISSN:1420-3049
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:The synthesis of the tetracyclic compounds 1-(4,5-dichloro-9,10-dihydro-9,10-ethanoanthracen-11-yl)-N-methylmethanamine (5) and 1-(1,8-dichloro-9,10-dihydro-9,10-ethanoanthracen-11-yl)-N-methylmethanamine (6) as a homologue of the anxiolytic and antidepressant drugs benzoctamine and maprotiline were described. The key intermediate aldehydes (3) and (4) were successfully synthesized via a [4 + 2] cycloaddition between acrolein and 1,8-dichloroanthracene. The synthesized compounds were investigated for antidepressant activity using the forced swimming test. Compounds (5), (6) and (3) showed significant reduction in the mice immobility indicating significant antidepressant effects. These compounds significantly reduced the immobility times at a dose 80 mg/kg by 84.0%, 86.7% and 71.1% respectively.
[Mh] Termos MeSH primário: Antracenos/síntese química
Ansiolíticos/síntese química
Antidepressivos/síntese química
Hidrocarbonetos Clorados/síntese química
[Mh] Termos MeSH secundário: Animais
Antracenos/química
Antracenos/farmacologia
Ansiolíticos/química
Ansiolíticos/farmacologia
Antidepressivos/química
Antidepressivos/farmacologia
Hidrocarbonetos Clorados/química
Hidrocarbonetos Clorados/farmacologia
Resposta de Imobilidade Tônica/efeitos dos fármacos
Maprotilina/química
Maprotilina/farmacologia
Camundongos
Estrutura Molecular
Natação
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (1-(1,8-dichloro-9,10-dihydro-9,10-ethanoanthracen-11-yl)-N-methylmethanamine); 0 (1-(4,5-dichloro-9,10-dihydro-9,10-ethanoanthracen-11-yl)-N-methylmethanamine); 0 (Anthracenes); 0 (Anti-Anxiety Agents); 0 (Antidepressive Agents); 0 (Hydrocarbons, Chlorinated); 2U1W68TROF (Maprotiline); 734MM7Y191 (benzoctamine)
[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:160108
[St] Status:MEDLINE


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[PMID]:26206340
[Au] Autor:Gunduz O; Topuz RD; Karadag CH; Ulugol A
[Ad] Endereço:Department of Medical Pharmacology, Faculty of Medicine, Trakya University, 22030-Edirne, Turkey.
[Ti] Título:Analysis of the anti-allodynic effects of combination of a synthetic cannabinoid and a selective noradrenaline re-uptake inhibitor in nerve injury-induced neuropathic mice.
[So] Source:Eur J Pain;20(3):465-71, 2016 Mar.
[Is] ISSN:1532-2149
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Combining drugs not only reduces specific adverse effects of each of the drug at a higher dose but also may lead to enhanced efficacy. Tapentadol is a recently discovered analgesic possessing µ-opioid receptor agonism and noradrenaline re-uptake inhibition in a single molecule. Taking into consideration, the pharmacological similarities between opioids and cannabinoids, we assumed that combination of cannabinoids with noradrenaline re-uptake inhibitors might also be effective. We therefore aimed to determine whether combining 1:1, 1:3 and 3:1 fixed ratios of the synthetic cannabinoid WIN 55,212-2 and the selective noradrenaline re-uptake inhibitor maprotiline exert anti-allodynic synergy on nerve-injured neuropathic mice. METHODS: Partial tight ligation of the sciatic nerve was made in mice; on pre-operative and post-operative 15 days basal mechanical allodynia, cold allodynia and motor function were assessed using von Frey filaments, hot/cold plate and rota rod apparatus. RESULTS: Mechanical and cold allodynia developed in all groups on post-operative 15 days. Development of cold allodynia was statistically significant in all groups (p < 0.05); therefore, cold allodynia was used in combination studies. As shown by isobolographic analysis, interactions of 1:1 and 3:1 ratios of WIN 55,212-2:maprotiline combinations were supra-additive, whereas 1:3 ratio was sub-additive. CONCLUSIONS: Overall, our data suggest that combination of a cannabinoid with a selective noradrenaline re-uptake inhibitor may offer a beneficial treatment option for neuropathic pain.
[Mh] Termos MeSH primário: Inibidores da Captação Adrenérgica/uso terapêutico
Benzoxazinas/uso terapêutico
Canabinoides/uso terapêutico
Hiperalgesia/tratamento farmacológico
Maprotilina/uso terapêutico
Morfolinas/uso terapêutico
Naftalenos/uso terapêutico
Neuralgia/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Temperatura Baixa
Relação Dose-Resposta a Droga
Combinação de Medicamentos
Quimioterapia Combinada
Hiperalgesia/etiologia
Hiperalgesia/psicologia
Ligadura
Masculino
Camundongos
Camundongos Endogâmicos BALB C
Atividade Motora/efeitos dos fármacos
Estimulação Física
Nervo Isquiático/lesões
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Adrenergic Uptake Inhibitors); 0 (Benzoxazines); 0 (Cannabinoids); 0 (Drug Combinations); 0 (Morpholines); 0 (Naphthalenes); 2U1W68TROF (Maprotiline); 5H31GI9502 (Win 55212-2)
[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:150725
[St] Status:MEDLINE
[do] DOI:10.1002/ejp.752


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[PMID]:25482049
[Au] Autor:Chew WS; Ong WY
[Ad] Endereço:Department of Anatomy, National University of Singapore, Singapore, 119260, Singapore.
[Ti] Título:Regulation of Calcium-Independent Phospholipase A2 Expression by Adrenoceptors and Sterol Regulatory Element Binding Protein-Potential Crosstalk Between Sterol and Glycerophospholipid Mediators.
[So] Source:Mol Neurobiol;53(1):500-517, 2016 Jan.
[Is] ISSN:1559-1182
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Calcium-independent phospholipase A2 (iPLA2) is an 85-kDa enzyme that releases docosahexaenoic acid (DHA) from glycerophospholipids. DHA can be metabolized to resolvins and neuroprotectins that have anti-inflammatory properties and effects on neural plasticity. Recent studies show an important role of prefrontal cortical iPLA2 in hippocampo-prefrontal cortical LTP and antidepressant-like effect of the norepinephrine reuptake inhibitor (NRI) antidepressant, maprotiline. In this study, we elucidated the cellular mechanisms through which stimulation of adrenergic receptors could lead to increased iPLA2 expression. Treatment of SH-SY5Y neuroblastoma cells with maprotiline, another tricyclic antidepressant with noradrenaline reuptake inhibiting properties, nortriptyline, and the adrenergic receptor agonist, phenylephrine, resulted in increased iPLA2ß mRNA expression. This increase was blocked by inhibitors to alpha-1 adrenergic receptor, mitogen-activated protein (MAP) kinase or extracellular signal-regulated kinase (ERK) 1/2, and sterol regulatory element-binding protein (SREBP). Maprotiline and phenylephrine induced binding of SREBP-2 to sterol regulatory element (SRE) region on the iPLA2 promoter, as determined by electrophoretic mobility shift assay (EMSA). Together, results indicate that stimulation of adrenoreceptors causes increased iPLA2 expression via MAP kinase/ERK 1/2 and SREBP, and suggest a possible mechanism for effect of CNS noradrenaline on neural plasticity and crosstalk between sterol and glycerophospholipid mediators, that may play a role in physiological or pathophysiological processes in the brain and other organs.
[Mh] Termos MeSH primário: Glicerofosfolipídeos/fisiologia
Fosfolipases A2 do Grupo VI/biossíntese
Receptor Cross-Talk/fisiologia
Receptores Adrenérgicos/fisiologia
Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo
[Mh] Termos MeSH secundário: Agonistas Adrenérgicos/farmacologia
Antagonistas de Receptores Adrenérgicos alfa 1/farmacologia
Antidepressivos/farmacologia
Linhagem Celular Tumoral
MAP Quinases Reguladas por Sinal Extracelular/metabolismo
Seres Humanos
Sistema de Sinalização das MAP Quinases/efeitos dos fármacos
Sistema de Sinalização das MAP Quinases/fisiologia
Maprotilina/farmacologia
Receptor Cross-Talk/efeitos dos fármacos
Esteróis/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Adrenergic Agonists); 0 (Adrenergic alpha-1 Receptor Antagonists); 0 (Antidepressive Agents); 0 (Glycerophospholipids); 0 (Receptors, Adrenergic); 0 (SREBF2 protein, human); 0 (Sterol Regulatory Element Binding Protein 2); 0 (Sterols); 2U1W68TROF (Maprotiline); EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases); EC 3.1.1.4 (Group VI Phospholipases A2); EC 3.1.1.4 (PLA2G6 protein, human)
[Em] Mês de entrada:1610
[Cu] Atualização por classe:171108
[Lr] Data última revisão:
171108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:141209
[St] Status:MEDLINE
[do] DOI:10.1007/s12035-014-9026-9


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[PMID]:26260446
[Au] Autor:Ide S; Satoyoshi H; Minami M; Satoh M
[Ad] Endereço:Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan. ide-si@igakuken.or.jp.
[Ti] Título:Amelioration of the reduced antinociceptive effect of morphine in the unpredictable chronic mild stress model mice by noradrenalin but not serotonin reuptake inhibitors.
[So] Source:Mol Pain;11:47, 2015 Aug 11.
[Is] ISSN:1744-8069
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Although alterations in not only the pain sensitivity but also the analgesic effects of opioids have been reported under conditions of stress, the influence of unpredictable chronic mild stress (UCMS) on the antinociceptive effects of opioid analgesics remains to be fully investigated. The present study examined the influence of UCMS on the thermal pain sensitivity and antinociceptive effects of two opioid analgesics, morphine (an agonist of opioid receptors) and tramadol (an agonist of µ-opioid receptor and an inhibitor of both noradrenaline and serotonin transporters). We also examined the effects of pretreatment with maprotiline (a noradrenaline reuptake inhibitor) and escitalopram (a serotonin reuptake inhibitor) on the antinociceptive action of morphine in mice under an UCMS condition. RESULTS: Unpredictable chronic mild stress did not affect the basal thermal pain sensitivity in a mouse hot-plate test. Although morphine dose-dependently induced thermal antinociceptive effects under both the UCMS and non-stress conditions, the thermal antinociceptive effect of 3 mg/kg morphine under the UCMS condition was significantly lower than under the non-stressed condition. Unlike the case with morphine, we observed no significant difference in the thermal antinociceptive effect of tramadol between the UCMS and non-stress conditions. Furthermore, the reduced thermal antinociceptive effect of 3 mg/kg morphine under the UCMS condition was significantly ameliorated by pretreatment with 10 mg/kg maprotiline but not 3 mg/kg escitalopram. Pretreatment with neither maprotiline nor escitalopram alone was associated with an antinociceptive effect under either condition. CONCLUSIONS: We demonstrated that the antinociceptive effect of morphine but not tramadol was reduced in mice that had experienced UCMS. The reduced antinociceptive effect of morphine under the UCMS condition was ameliorated by pretreatment with maprotiline but not escitalopram. These results suggest that the reduced antinociceptive effects of morphine under conditions of chronic stress may be ameliorated by activation of the noradrenergic but not the serotonergic system.
[Mh] Termos MeSH primário: Analgésicos/farmacologia
Morfina/farmacologia
Norepinefrina/farmacologia
Inibidores da Captação de Serotonina/farmacologia
Estresse Fisiológico/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Doença Crônica
Citalopram/farmacologia
Modelos Animais de Doenças
Masculino
Maprotilina/farmacologia
Camundongos Endogâmicos BALB C
Temperatura Ambiente
Tramadol/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Analgesics); 0 (Serotonin Uptake Inhibitors); 0DHU5B8D6V (Citalopram); 2U1W68TROF (Maprotiline); 39J1LGJ30J (Tramadol); 76I7G6D29C (Morphine); X4W3ENH1CV (Norepinephrine)
[Em] Mês de entrada:1603
[Cu] Atualização por classe:150814
[Lr] Data última revisão:
150814
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150812
[St] Status:MEDLINE
[do] DOI:10.1186/s12990-015-0051-0


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[PMID]:26155740
[Au] Autor:Dean SN; van Hoek ML
[Ad] Endereço:a National Center for Biodefense and Infectious Diseases ; Manassas , VA , USA.
[Ti] Título:Screen of FDA-approved drug library identifies maprotiline, an antibiofilm and antivirulence compound with QseC sensor-kinase dependent activity in Francisella novicida.
[So] Source:Virulence;6(5):487-503, 2015.
[Is] ISSN:2150-5608
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Development of new therapeutics against Select Agents such as Francisella is critical preparation in the event of bioterrorism. Testing FDA-approved drugs for this purpose may yield new activities unrelated to their intended purpose and may hasten the discovery of new therapeutics. A library of 420 FDA-approved drugs was screened for antibiofilm activity against a model organism for human tularemia, Francisella (F.) novicida, excluding drugs that significantly inhibited growth. The initial screen was based on the 2-component system (TCS) dependent biofilm effect, thus, the QseC dependence of maprotiline anti-biofilm action was demonstrated. By comparing their FDA-approved uses, chemical structures, and other properties of active drugs, toremifene and polycyclic antidepressants maprotiline and chlorpromazine were identified as being highly active against F. novicida biofilm formation. Further down-selection excluded toremifene for its membrane active activity and chlorpromazine for its high antimicrobial activity. The mode of action of maprotiline against F. novicida was sought. It was demonstrated that maprotiline was able to significantly down-regulate the expression of the virulence factor IglC, encoded on the Francisella Pathogenicity Island (FPI), suggesting that maprotiline is exerting an effect on bacterial virulence. Further studies showed that maprotiline significantly rescued F. novicida infected wax worm larvae. In vivo studies demonstrated that maprotiline treatment could prolong time to disease onset and survival in F. novicida infected mice. These results suggest that an FDA-approved drug such as maprotiline has the potential to combat Francisella infection as an antivirulence agent, and may have utility in combination with antibiotics.
[Mh] Termos MeSH primário: Biofilmes/efeitos dos fármacos
Francisella/efeitos dos fármacos
Maprotilina/química
Maprotilina/farmacologia
Proteínas Quinases/metabolismo
Tularemia/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Biofilmes/crescimento & desenvolvimento
Modelos Animais de Doenças
Feminino
Francisella/genética
Francisella/metabolismo
Francisella/patogenicidade
Regulação Bacteriana da Expressão Gênica
Ilhas Genômicas
Histidina Quinase
Larva/microbiologia
Maprotilina/isolamento & purificação
Maprotilina/uso terapêutico
Camundongos
Testes de Sensibilidade Microbiana
Mariposas/microbiologia
Proteínas Quinases/química
Tularemia/microbiologia
Estados Unidos
United States Food and Drug Administration
Virulência/efeitos dos fármacos
Fatores de Virulência/genética
Fatores de Virulência/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Virulence Factors); 2U1W68TROF (Maprotiline); EC 2.7.- (Protein Kinases); EC 2.7.13.1 (Histidine Kinase)
[Em] Mês de entrada:1604
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150710
[St] Status:MEDLINE
[do] DOI:10.1080/21505594.2015.1046029


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[PMID]:26055396
[Au] Autor:Feldmann EA; Cavanagh J
[Ad] Endereço:a Department of Molecular and Structural Biochemistry; North Carolina State University ; Raleigh , NC , USA.
[Ti] Título:Teaching old drugs new tricks: Addressing resistance in Francisella.
[So] Source:Virulence;6(5):414-6, 2015.
[Is] ISSN:2150-5608
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Biofilmes/efeitos dos fármacos
Francisella/efeitos dos fármacos
Maprotilina/química
Maprotilina/farmacologia
Proteínas Quinases/metabolismo
Tularemia/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Feminino
[Pt] Tipo de publicação:COMMENT; EDITORIAL
[Nm] Nome de substância:
2U1W68TROF (Maprotiline); EC 2.7.- (Protein Kinases)
[Em] Mês de entrada:1604
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150610
[St] Status:MEDLINE
[do] DOI:10.1080/21505594.2015.1053689


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[PMID]:25186516
[Au] Autor:Ahmad SA; Mujawar Q; Bawardi NA
[Ad] Endereço:Department of Pediatric Emergency King Khalid University Hospital King Saud University Riyadh, Saudi Arabia.
[Ti] Título:A 14-month-old child with staring gaze and a blocked heart.
[So] Source:Pediatr Emerg Care;30(9):670-2, 2014 Sep.
[Is] ISSN:1535-1815
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Inibidores da Captação Adrenérgica/envenenamento
Transtornos da Consciência/etiologia
Bloqueio Cardíaco/induzido quimicamente
Maprotilina/envenenamento
Convulsões/etiologia
[Mh] Termos MeSH secundário: Antidepressivos de Segunda Geração/envenenamento
Diagnóstico Diferencial
Eletrocardiografia
Escala de Coma de Glasgow
Bloqueio Cardíaco/diagnóstico
Seres Humanos
Lactente
Masculino
Envenenamento/complicações
Envenenamento/diagnóstico
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Adrenergic Uptake Inhibitors); 0 (Antidepressive Agents, Second-Generation); 2U1W68TROF (Maprotiline)
[Em] Mês de entrada:1505
[Cu] Atualização por classe:140904
[Lr] Data última revisão:
140904
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140905
[St] Status:MEDLINE
[do] DOI:10.1097/PEC.0000000000000249



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