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[PMID]:29273565
[Au] Autor:Maier MY; Luks L; Baudendistel OR; Wittmann V; Dietrich DR
[Ad] Endereço:Human and Environmental Toxicology, Department of Biology, University of Konstanz, Germany; Konstanz Research School Chemical Biology (KoRS-CB), University of Konstanz, Germany.
[Ti] Título:Identification of d-amino acid oxidase and propiverine interaction partners and their potential role in the propiverine-mediated nephropathy.
[So] Source:Chem Biol Interact;281:69-80, 2018 Feb 01.
[Is] ISSN:1872-7786
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:Propiverine, a frequently-prescribed pharmaceutical for the treatment of symptoms associated with overactive bladder syndrome, provoked massive intranuclear and cytosolic protein inclusions in rat proximal tubule epithelium, primarily consisting of the peroxisomal targeting signal 1 (PTS1) containing protein d-amino acid oxidase (DAAO). As this type of nephropathy was also observed for other drugs, the aim was to determine whether propiverine interferes with trafficking and/or import of peroxisomal proteins. To elucidate this, DAAO- and propiverine-specific interaction partners from human HEK293 and rat WKPT cell lines and rat kidney and liver homogenate were determined using co-immunoprecipitation with subsequent nano-ESI-LC-MS/MS analyses. Corroboration of the role of DAAO- and/or propiverine-specific interaction partners in the drug-induced DAAO accumulation was sought via specific immunofluorescence staining of rat kidney sections from control and propiverine-treated rats. Above analyses demonstrated the interaction of propiverine with several protein classes, foremost peroxisomal proteins (DAAO, MFE2, HAOX2) and proteins of the protein quality control system, i.e. chaperones (HSP70 and DnaJ co-chaperones), proteases and proteasomal proteins (regulatory subunits of the 26S proteasome; Rpn1/2). The immunofluorescence analysis revealed mislocalization of many PTS1-proteins (DAAO, CAT, MFE2, ACOX1, EHHADH) in rat renal sections, strongly suggesting that propiverine primarily binds to PTS1 proteins resulting in the formation of PTS1 but not PTS2 or peroxisomal membrane protein (PMP) accumulations. Moreover, chaperones involved in peroxisomal trafficking (HSC70, DnaJB1) and peroxisomal biogenesis factor proteins (PEX3, PEX5, PEX7), also presented with distinct mislocalization patterns. Concomitantly, an increased number of peroxisomes was observed, suggestive of a compensatory mechanism for the presumably suboptimally functioning peroxisomes. Overall, the data presented suggested that propiverine interacts exclusively with DAAO or with a selected number of PTS1 proteins. The consequence of this interaction is the abrogated trafficking and peroxisomal import of PTS1 proteins concomitant with their nuclear and cytosolic accumulation due to inhibited degradation and imbalanced protein homeostasis.
[Mh] Termos MeSH primário: Aminoácido Oxirredutases/metabolismo
Benzilatos/metabolismo
Nefropatias Diabéticas/etiologia
[Mh] Termos MeSH secundário: 17-Hidroxiesteroide Desidrogenases/metabolismo
Oxirredutases do Álcool/metabolismo
Aminoácido Oxirredutases/química
Aminoácido Oxirredutases/genética
Animais
Benzilatos/química
Benzilatos/toxicidade
Linhagem Celular
Cromatografia Líquida de Alta Pressão
Células HEK293
Seres Humanos
Imunoprecipitação
Rim/metabolismo
Rim/patologia
Fígado/metabolismo
Microscopia Confocal
Chaperonas Moleculares/metabolismo
Proteína Multifuncional do Peroxissomo-2/metabolismo
Receptor 1 de Sinal de Orientação para Peroxissomos/química
Receptor 1 de Sinal de Orientação para Peroxissomos/metabolismo
Transporte Proteico/efeitos dos fármacos
Ratos
Proteínas Recombinantes de Fusão/biossíntese
Proteínas Recombinantes de Fusão/química
Espectrometria de Massas por Ionização por Electrospray
Espectrometria de Massas em Tandem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzilates); 0 (Molecular Chaperones); 0 (Peroxisome-Targeting Signal 1 Receptor); 0 (Recombinant Fusion Proteins); 468GE2241L (propiverine); EC 1.1.- (17-Hydroxysteroid Dehydrogenases); EC 1.1.- (Alcohol Oxidoreductases); EC 1.1.1.119 (Hsd17b4 protein, rat); EC 1.4.- (Amino Acid Oxidoreductases); EC 4.2.1.107 (Peroxisomal Multifunctional Protein-2)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180129
[Lr] Data última revisão:
180129
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171224
[St] Status:MEDLINE


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[PMID]:28120444
[Au] Autor:Orgen S; Deliktas H; Sahin H; Gedik A; Nergis Y
[Ad] Endereço:Department of Urology, Batman State Hospital, Batman, Turkey.
[Ti] Título:Histopathologic and Urodynamic Effects of the Anticholinergic Drugs Oxybutynin, Tolterodine, and Trospium on the Bladder.
[So] Source:Low Urin Tract Symptoms;9(1):52-56, 2017 Jan.
[Is] ISSN:1757-5672
[Cp] País de publicação:Australia
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: This study aimed to evaluate the effects of intravesical instillation of the anticholinergic drugs oxybutynin, tolterodine, and trospium on bladder capacity and histopathological changes in the bladder mucosa. METHODS: The study included 20 male New Zealand white rabbits that were randomly allocated to four groups of five. In the oxybutynin, tolterodine, and trospium groups, the drugs used were 1 mg/kg of crushed tablet mixed with 5 mL of saline, instilled intravesically once per day for 4 weeks. The control group was administered only 5 mL of saline once per day for 4 weeks. Urodynamic measurement of the bladder was made before and after treatment. At the end of the treatment the animals were killed and the bladders were evaluated histopathologically. RESULTS: There were no significant differences between pre- and post-treatment bladder capacity in any of the groups (P > 0.05). Histopathological evaluation showed that the mucosal epithelium was intact and there was minor inflammation in the control group and oxybutynin group (P > 0.05), whereas there was destruction of the mucosal epithelium and findings of diffuse inflammation in the tolterodine (P = 0.014) and trospium (P = 0.014) groups. CONCLUSION: Intravesical oxybutynin treatment was observed to be safe; however, a single daily dose of oxybutynin may not be sufficient to increase bladder capacity. Intravesical use of trospium and tolterodine at high doses caused epithelial destruction and diffuse inflammation in the bladder mucosa. The irritation associated with epithelial destruction and inflammation prevented an increase in bladder capacity.
[Mh] Termos MeSH primário: Benzilatos/farmacologia
Ácidos Mandélicos/farmacologia
Antagonistas Muscarínicos/farmacologia
Nortropanos/farmacologia
Tartarato de Tolterodina/farmacologia
Bexiga Urinária/efeitos dos fármacos
Agentes Urológicos/farmacologia
[Mh] Termos MeSH secundário: Animais
Masculino
Coelhos
Distribuição Aleatória
Urotélio/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzilates); 0 (Mandelic Acids); 0 (Muscarinic Antagonists); 0 (Nortropanes); 0 (Urological Agents); 1E6682427E (trospium chloride); 5T619TQR3R (Tolterodine Tartrate); K9P6MC7092 (oxybutynin)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170606
[Lr] Data última revisão:
170606
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170126
[St] Status:MEDLINE
[do] DOI:10.1111/luts.12096


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[PMID]:28074677
[Au] Autor:Kosilov K; Loparev S; Kuzina I; Shakirova O; Zhuravskaya N; Lobodenko A
[Ad] Endereço:a Department of Social Sciences , Far Eastern Federal University , Vladivostok , Russia.
[Ti] Título:The effective tool for self-assessment of adherence to treatment in patients with benign prostatic obstruction and overactive bladder symptoms.
[So] Source:Aging Male;20(1):39-44, 2017 Mar.
[Is] ISSN:1473-0790
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Study of validity of the Medication Adherence Self-Report Inventory (MASRI) for use in clinical practice to treat patients with benign prostatic obstruction (BPO) accompanied with overactive bladder (OAB) symptoms. METHODS: During 12 weeks of the randomized study, 452 patients with BPO and OAB symptoms (mean age of 61.3 (12.7)) were studied for adherence to the treatment with Tamsulosin, Solifenacin and Trospium using the MASRI. External monitoring instruments included the Brief Medication Questionnaire (BMQ) and the visual remaining pill count. The state of the prostate gland and the lower urinary tract was monitored using questionnaires I-PSS, OAB Awareness Tool, uroflowmetry and voiding diaries. RESULT: Correlation between the percentage of men non-adherent to treatment (MASRI) and the percentage of patients having a belief barrier on the screen of the BMQ was r = 0.89, p ≤0.05, r = 0.92, p ≤0.01, r = 0.85, p ≤0.05, a number of missed doses on the Regimen Screen of the BMQ was r = 0.79; p ≤0.05; r = 0.81; p ≤0.05; r = 0.75, p ≤0.05, a number of non-adherent patients according to the BMQ was r = 0.83 (p ≤0.05), r = 0.88 (p ≤0.05), r = 0.79, p ≤0.05, the results of the pill count were r = 0.65-0.76; p ≤0.05-0.01. These data confirm high validity of the MASRI. CONCLUSION: The MASRI is a valid tool for rapid assessment of adherence to treatment of patients with BPO and OAB receiving Tamsulosin and antimuscarinic drugs and may be recommended for use in clinical practice.
[Mh] Termos MeSH primário: Adesão à Medicação
Hiperplasia Prostática/tratamento farmacológico
Autoavaliação
Bexiga Urinária Hiperativa/tratamento farmacológico
[Mh] Termos MeSH secundário: Idoso
Benzilatos/uso terapêutico
Autoavaliação Diagnóstica
Quimioterapia Combinada
Seres Humanos
Masculino
Meia-Idade
Antagonistas Muscarínicos/uso terapêutico
Nortropanos/uso terapêutico
Hiperplasia Prostática/complicações
Succinato de Solifenacina/uso terapêutico
Sulfonamidas/uso terapêutico
Inquéritos e Questionários
Bexiga Urinária Hiperativa/complicações
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL; VALIDATION STUDIES
[Nm] Nome de substância:
0 (Benzilates); 0 (Muscarinic Antagonists); 0 (Nortropanes); 0 (Sulfonamides); 1E6682427E (trospium chloride); G3P28OML5I (tamsulosin); KKA5DLD701 (Solifenacin Succinate)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170925
[Lr] Data última revisão:
170925
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170112
[St] Status:MEDLINE
[do] DOI:10.1080/13685538.2016.1247435


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[PMID]:27087507
[Au] Autor:Leng J; Liao L; Wan B; Du C; Li W; Xie K; Shen Z; Xu Z; Wu S; Fang Z; Ma L; Han S; Feustel C; Yang Y; Madersbacher H
[Ad] Endereço:Renji Hospital Affiliated to Shanghai JiaoTong University School of Medicine, Shanghai, China.
[Ti] Título:Results of a randomized, double-blind, active-controlled clinical trial with propiverine extended release 30 mg in patients with overactive bladder.
[So] Source:BJU Int;119(1):148-157, 2017 Jan.
[Is] ISSN:1464-410X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: To compare the efficacy and safety of the 30 mg extended release (ER) formulation of propiverine hydrochloride with the 4 mg ER formulation of tolterodine tartrate in patients with overactive bladder (OAB) in a non-inferiority trial. PATIENTS AND METHODS: Eligible patients, aged 18-75 years and with symptoms of OAB, were enrolled in this multicentre, randomized, double-blind, parallel-group, active-controlled study. After a 2-week screening period, patients were randomized at a 1:1 ratio to receive either propiverine ER 30 mg or tolterodine ER 4 mg daily during the 8-week treatment period. Efficacy was assessed using a 3-day voiding diary and patient's self-reported assessment of treatment effect. Safety assessment included recording of adverse events, laboratory test results, measurement of post-void residual urine and electrocardiograms. RESULTS: A total of 324 patients (244 female and 80 male) were included in the study. Both active treatments improved the variables included in the voiding diary and in the patient's self-reported assessment. The change from baseline in the number of voidings per 24 h was significantly greater in the propiverine ER 30 mg group compared with the tolterodine ER 4 mg group after 8 weeks of treatment (full analysis set [FAS] -4.6 ± 4.1 vs -3.8 ± 5.1; P = 0.005). Significant improvements were also observed for the change of urgency incontinence episodes after 2 weeks (P = 0.026) and 8 weeks (P = 0.028) of treatment when comparing propiverine ER 30 mg with tolterodine ER 4 mg. Both treatments were well tolerated, with a similar frequency of adverse drug reactions in both the propiverine ER 30 mg and tolterodine ER 4 mg groups (FAS 40.7 vs 39.5%; P = 0.8). More patients treated with tolterodine ER 4 mg discontinued the treatment because of adverse drug reactions compared with propiverine ER 30 mg (7.4 vs 3.1%). CONCLUSIONS: Propiverine ER 30 mg was confirmed to be an effective and well-tolerated treatment option for patients with OAB symptoms. This first head-to-head study showed non-inferiority of propiverine ER 30 mg compared with tolterodine ER 4 mg.
[Mh] Termos MeSH primário: Benzilatos/administração & dosagem
Antagonistas Muscarínicos/administração & dosagem
Tartarato de Tolterodina/administração & dosagem
Bexiga Urinária Hiperativa/tratamento farmacológico
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Preparações de Ação Retardada
Método Duplo-Cego
Feminino
Seres Humanos
Masculino
Meia-Idade
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Benzilates); 0 (Delayed-Action Preparations); 0 (Muscarinic Antagonists); 468GE2241L (propiverine); 5T619TQR3R (Tolterodine Tartrate)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170524
[Lr] Data última revisão:
170524
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160419
[St] Status:MEDLINE
[do] DOI:10.1111/bju.13500


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[PMID]:26961980
[Au] Autor:Luks L; Sacchi S; Pollegioni L; Dietrich DR
[Ad] Endereço:Human and Environmental Toxicology, University of Konstanz, Universitätsstrasse 10, 78457, Constance, Germany.
[Ti] Título:Novel insights into renal D-amino acid oxidase accumulation: propiverine changes DAAO localization and peroxisomal size in vivo.
[So] Source:Arch Toxicol;91(1):427-437, 2017 Jan.
[Is] ISSN:1432-0738
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Chronic exposure to propiverine, a frequently prescribed pharmaceutical for treatment of overactive bladder and incontinence, provokes massive protein accumulation in the cytosol and nucleus of renal proximal tubule epithelial cells in rats. Previously, the accumulating protein was identified as D-amino acid oxidase (DAAO), a peroxisomal flavoenzyme expressed in kidney, liver and brain. The cellular mechanism of propiverine-induced DAAO accumulation, however, remains unexplained and poorly characterized. Therefore, to further increase the understanding of DAAO accumulation in rat kidney, this study aimed to characterize DAAO accumulations using differential immunofluorescent staining of rat kidney sections as well as in vitro binding analyses and proteasomal activity studies. We demonstrated that propiverine is neither a ligand of DAAO nor an inhibitor of the proteasome in vitro. However, propiverine treatment resulted in a significant decrease of peroxisomal size in rat proximal tubule epithelial cells. Moreover, peroxisomal catalase also accumulated in the cytosol and nuclei of propiverine-treated rats concurrently with DAAO. Taken together, our study indicates that propiverine treatment affects the trafficking and/or degradation of peroxisomal proteins such as DAAO and catalase by a so far unique and unknown mechanism.
[Mh] Termos MeSH primário: Benzilatos/efeitos adversos
Antagonistas Colinérgicos/efeitos adversos
D-Aminoácido Oxidase/metabolismo
Túbulos Renais Proximais/efeitos dos fármacos
Peroxissomos/efeitos dos fármacos
Agentes Urológicos/efeitos adversos
[Mh] Termos MeSH secundário: Animais
Benzilatos/administração & dosagem
Catalase/metabolismo
Núcleo Celular/efeitos dos fármacos
Núcleo Celular/enzimologia
Núcleo Celular/metabolismo
Antagonistas Colinérgicos/administração & dosagem
Citosol/efeitos dos fármacos
Citosol/enzimologia
Citosol/metabolismo
D-Aminoácido Oxidase/química
D-Aminoácido Oxidase/genética
Relação Dose-Resposta a Droga
Estabilidade Enzimática/efeitos dos fármacos
Feminino
Seres Humanos
Túbulos Renais Proximais/citologia
Túbulos Renais Proximais/enzimologia
Masculino
Camundongos
Tamanho das Organelas/efeitos dos fármacos
Peroxissomos/metabolismo
Transporte Proteico/efeitos dos fármacos
Ratos
Ratos Endogâmicos F344
Proteínas Recombinantes/química
Proteínas Recombinantes/metabolismo
Testes de Toxicidade Crônica
Agentes Urológicos/administração & dosagem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzilates); 0 (Cholinergic Antagonists); 0 (Recombinant Proteins); 0 (Urological Agents); 468GE2241L (propiverine); EC 1.11.1.6 (Catalase); EC 1.4.3.3 (D-Amino-Acid Oxidase)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160311
[St] Status:MEDLINE
[do] DOI:10.1007/s00204-016-1685-z


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[PMID]:28247723
[Au] Autor:Krivoborodov GG; Tur EI; Efremov NS; Shkolnikov ME
[Ad] Endereço:Department of Faculty Surgery, Urology of the Medical Faculty RNSMU n.a. N.I. Pirogov, RCRC of Gerontology.
[Ti] Título:[High doses of trospium chloride in patients with idiopathic overactive bladder. Data of large-scale, multicenter observational program Resource].
[So] Source:Urologiia;(4):29-34, 2016 Aug.
[Is] ISSN:1728-2985
[Cp] País de publicação:Russia (Federation)
[La] Idioma:rus
[Ab] Resumo:PURPOSE: Evaluation of the efficacy and safety of different doses of trospium chloride in patients with idiopathic overactive bladder. MATERIALS AND METHODS: Large-scale observational program "Resource" included 669 patients with idiopathic OAB - 359 women and 310 men. At the first visit, all patients were assigned to use of trospium chloride at a standard dose of 45 mg per day. The results of treatment were evaluated during follow-up visits at 3, 6, 9 and 12 weeks. Depending on the results of examination, the dose was reduced in the presence of adverse events and increased in case of insufficient treatment effects. RESULTS: After 12 weeks, 102 patients have been receiving the drug at a dose of 30 mg/day, 241 - at a dose of 45 mg/day, 257 - at a dose of 60 mg/day, and 22 - at a dose of 75 mg/day. CONCLUSIONS: Individual approach to the selection of doses of trospium chloride in patients with idiopathic OAB can be quite effective and safe measure to achieve optimal clinical outcome with a good safety profile.
[Mh] Termos MeSH primário: Benzilatos/uso terapêutico
Antagonistas Colinérgicos/uso terapêutico
Nortropanos/uso terapêutico
Bexiga Urinária Hiperativa/tratamento farmacológico
[Mh] Termos MeSH secundário: Benzilatos/administração & dosagem
Benzilatos/efeitos adversos
Antagonistas Colinérgicos/administração & dosagem
Antagonistas Colinérgicos/efeitos adversos
Relação Dose-Resposta a Droga
Feminino
Seres Humanos
Masculino
Meia-Idade
Nortropanos/administração & dosagem
Nortropanos/efeitos adversos
Qualidade de Vida
Bexiga Urinária Hiperativa/psicologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (Benzilates); 0 (Cholinergic Antagonists); 0 (Nortropanes); 1E6682427E (trospium chloride)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171026
[Lr] Data última revisão:
171026
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170302
[St] Status:MEDLINE


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[PMID]:27765726
[Au] Autor:Tadken T; Weiss M; Modess C; Wegner D; Roustom T; Neumeister C; Schwantes U; Schulz HU; Weitschies W; Siegmund W
[Ad] Endereço:Department of Clinical Pharmacology, Center of Drug Absorption and Transport, University Medicine of Greifswald, Greifswald, Germany.
[Ti] Título:Trospium chloride is absorbed from two intestinal "absorption windows" with different permeability in healthy subjects.
[So] Source:Int J Pharm;515(1-2):367-373, 2016 Dec 30.
[Is] ISSN:1873-3476
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Intestinal P-glycoprotein is regio-selectively expressed and is a high affinity, low capacity efflux carrier for the cationic, poorly permeable trospium. Organic cation transporter 1 (OCT1) provides lower affinity but higher capacity for trospium uptake. To evaluate regional intestinal permeability, absorption profiles after gastric infusion of trospium chloride (30mg/250ml=[I] ) for 6h and after swallowing 30mg immediate-release tablets in fasted and fed healthy subjects, were evaluated using an inverse Gaussian density function to model input rate and mean absorption time (MAT). Trospium chloride was slowly absorbed (MAT ∼10h) after gastric infusion involving two processes with different input rates, peaking at about 3h and 7h. Input rates and MAT were influenced by dosage form and meal. In conclusion, trospium is absorbed from two "windows" located in the jejunum and cecum/ascending colon, whose uptake capacity might result from local abundance and functional interplay of P-glycoprotein and OCT1.
[Mh] Termos MeSH primário: Benzilatos/metabolismo
Ceco/metabolismo
Colo Ascendente/metabolismo
Absorção Intestinal/fisiologia
Jejuno/metabolismo
Nortropanos/metabolismo
[Mh] Termos MeSH secundário: Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo
Adulto
Feminino
Voluntários Saudáveis
Seres Humanos
Masculino
Transportador 1 de Cátions Orgânicos/metabolismo
Permeabilidade
Comprimidos/metabolismo
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ATP-Binding Cassette, Sub-Family B, Member 1); 0 (Benzilates); 0 (Nortropanes); 0 (Organic Cation Transporter 1); 0 (Tablets); 1E6682427E (trospium chloride)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161106
[St] Status:MEDLINE


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[PMID]:27750360
[Au] Autor:Sakakibara F; Takahama K; Nanri M; Sasaki E
[Ad] Endereço:Drug Discovery & Development II, Taiho Pharmaceutical Co., Ltd., Tsukuba, Japan.
[Ti] Título:Pharmacological Properties of Propiverine Contribute to Improving Lower Urinary Tract Dysfunctions in Rats with Spinal Cord Injuries.
[So] Source:Drug Res (Stuttg);66(9):464-469, 2016 Sep.
[Is] ISSN:2194-9387
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Patients with spinal cord injury (SCI) usually develop lower urinary tract dysfunctions, including detrusor overactivity which is also known to be a risk factor for upper urinary tract dysfunction. Antimuscarinic agents, such as propiverine, have been used clinically for the treatment of detrusor overactivity. Also, propiverine has been known to possess antagonistic activity against L-type Ca channels and transient receptor potential vanilloid subtype 1 (TRPV1), in addition to activity against muscarinic receptors. These mechanisms of action may contribute to improving detrusor overactivity in SCI. We therefore investigated the effects of antagonists of these mechanisms on non-voiding contraction (NVC) in SCI rats that are similar to clinical cases of detrusor overactivity, and considered whether these action mechanisms contribute to the incidence of NVC in SCI. Cystometry was performed in rats 4 weeks after spinal transection. Urinary functions were evaluated before and after intravenous administration of propiverine and specific antagonists for muscarinic receptors (atropine), L-type Ca channels (verapamil), and TRPV1 (capsazepine). Propiverine markedly decreased the amplitude pressure of NVC in SCI rats, which was partially inhibited by atropine. Verapamil also suppressed the amplitude pressure of NVC to the same degree as propiverine. NVC disappeared almost completely after C-fiber desensitization, although capsazepine exerted no evident effects. These findings suggest that muscarinic receptors, L-type Ca channels, and C-fiber afferent nerves contribute to the incidence of detrusor overactivity in SCI, and a drug that has multiple antagonistic effects, such as propiverine, is very effective for the treatment of lower urinary tract dysfunctions in SCI.
[Mh] Termos MeSH primário: Benzilatos/antagonistas & inibidores
Traumatismos da Medula Espinal/tratamento farmacológico
Bexiga Urinária Hiperativa/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Atropina/farmacologia
Benzilatos/uso terapêutico
Capsaicina/análogos & derivados
Capsaicina/farmacologia
Feminino
Antagonistas Muscarínicos/uso terapêutico
Ratos
Traumatismos da Medula Espinal/complicações
Bexiga Urinária/efeitos dos fármacos
Bexiga Urinária Hiperativa/complicações
Verapamil/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzilates); 0 (Muscarinic Antagonists); 468GE2241L (propiverine); 7C0697DR9I (Atropine); CJ0O37KU29 (Verapamil); LFW48MY844 (capsazepine); S07O44R1ZM (Capsaicin)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170505
[Lr] Data última revisão:
170505
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161018
[St] Status:MEDLINE


  9 / 823 MEDLINE  
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[PMID]:27668698
[Au] Autor:Gatchev E; Petkova N; Braeter M; de Mey C
[Ti] Título:Ocular safety of propiverine hydrochloride in elderly patients with primary open- and narrow-angle glaucoma
.
[So] Source:Int J Clin Pharmacol Ther;54(12):977-986, 2016 Dec.
[Is] ISSN:0946-1965
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Propiverine hydrochloride (P4) is an antimuscarinic drug used in overactive bladder syndrome. METHODS: Two studies were performed: one in 24 patients with open-angle glaucoma (OAG) treated with topical ß-blockers, one in 24 patients with narrow-angle glaucoma (NAG) treated with pilocarpine ± topical ß-blockers. Patients were treated in randomized, placebo-controlled, double-blind parallel-group fashion (15 : 9 attribution to P4 vs. placebo (PL)). TREATMENTS: Single-blind PL dose in the morning of day 1 for baseline; double-blind 15 mg P4 or matched placebo t.i.d. from the afternoon of day 1 until the morning of day 7. RESULTS: In the morning of day 7, trough mean serum P4 concentrations were 169.4 ng/mL (CV (coefficient of variation): 0.55) and 140.7 ng/mL (CV: 0.56) in OAG and NAG; at 3:15 hours after dosing: 237.4 ng/mL (CV: 0.47) and 212.4 ng/mL P4 (CV: 0.38), respectively. P4-treatment led to a prompt (OAG) or more gradient (NAG) increase in pupil diameter (PUD), with a maximum difference from PL of 0.97 mm (95% confidence interval (CI): 0.67 - 1.27) and 0.87 mm (95% CI: 0.36 - 1.39) in OAG and NAG, respectively. However, there was no average increase in intraocular pressure (IOP) or increase in noteworthy safety-relevant individual IOP values (or changes thereof). There was no effect on visual acuity or accommodation. CONCLUSIONS: 1-week treatment with P4 appeared to be safe 1) in OAG patients treated with topical ß-blockers and 2) in NAG patients treated with topical pilocarpine ± ß-blockers, irrespective of whether the eyes had previously been treated with glaucoma surgery or laser therapy.
.
[Mh] Termos MeSH primário: Benzilatos/efeitos adversos
Glaucoma de Ângulo Fechado/tratamento farmacológico
Glaucoma de Ângulo Aberto/tratamento farmacológico
Antagonistas Muscarínicos/efeitos adversos
[Mh] Termos MeSH secundário: Antagonistas Adrenérgicos beta/uso terapêutico
Idoso
Benzilatos/sangue
Método Duplo-Cego
Feminino
Seres Humanos
Pressão Intraocular/efeitos dos fármacos
Masculino
Meia-Idade
Método Simples-Cego
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Adrenergic beta-Antagonists); 0 (Benzilates); 0 (Muscarinic Antagonists); 468GE2241L (propiverine)
[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:160927
[St] Status:MEDLINE


  10 / 823 MEDLINE  
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Texto completo
[PMID]:27374291
[Au] Autor:Ito Y; Kashiwabara M; Yoshida A; Hikiyama E; Onoue S; Yamada S
[Ad] Endereço:Deaparment of Pharmacokinetics and Pharmacodynamics, Graduate School of Pharmaceutical Sciences, University of Shizuoka.
[Ti] Título:Muscarinic Receptor Binding in Rat Bladder Urothelium and Detrusor Muscle by Intravesical Solifenacin.
[So] Source:Biol Pharm Bull;39(7):1167-71, 2016.
[Is] ISSN:1347-5215
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:Solifenacin is an antimuscarinic agent used to treat symptoms of overactive bladder. Pharmacologically significant amounts of solifenacin were excreted in the urine of humans taking a clinical dose of this drug. The aim of this study is to measure muscarinic receptor binding in the bladder urothelium and detrusor muscles of rats following the intravesical instillation of solifenacin. Muscarinic receptors were measured by radioreceptor assay using [N-methyl-(3)H]scopolamine methyl chloride ([(3)H]NMS), a selective radioligand of muscarinic receptors. Solifenacin showed concentration-dependent inhibition of specific [(3)H]NMS binding in the bladder urothelium and detrusor muscle of rats, with no significant difference in Ki values or Hill coefficients between these tissues. Following the intravesical instillation of solifenacin, there was significant muscarinic receptor binding (increase in Kd for specific [(3)H]NMS binding) in the bladder urothelium and detrusor muscle of rats. Similar bladder muscarinic receptor binding was observed by the intravesical instillation of oxybutynin, but not with trospium. In conclusion, the present study has demonstrated that solifenacin binds muscarinic receptors not only in the detrusor muscle but also in the bladder urothelium with high affinity. These bladder muscarinic receptors may be significantly affected by solifenacin excreted in the urine.
[Mh] Termos MeSH primário: Antagonistas Muscarínicos/farmacologia
Músculo Liso/metabolismo
Receptores Muscarínicos/metabolismo
Succinato de Solifenacina/farmacologia
Bexiga Urinária/metabolismo
Agentes Urológicos/farmacologia
Urotélio/metabolismo
[Mh] Termos MeSH secundário: Administração Intravesical
Animais
Benzilatos/farmacologia
Masculino
Ácidos Mandélicos/farmacologia
Nortropanos/farmacologia
Ratos Sprague-Dawley
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzilates); 0 (Mandelic Acids); 0 (Muscarinic Antagonists); 0 (Nortropanes); 0 (Receptors, Muscarinic); 0 (Urological Agents); 1E6682427E (trospium chloride); K9P6MC7092 (oxybutynin); KKA5DLD701 (Solifenacin Succinate)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170127
[Lr] Data última revisão:
170127
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160705
[St] Status:MEDLINE
[do] DOI:10.1248/bpb.b16-00194



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