Base de dados : MEDLINE
Pesquisa : D27.505.519.625.375.425.712 [Categoria DeCS]
Referências encontradas : 261 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 27 ir para página                         

  1 / 261 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29334795
[Au] Autor:Lazewska D; Kiec-Kononowicz K
[Ad] Endereço:a Department of Technology and Biotechnology of Drugs , Jagiellonian University Medical College , Kraków , Poland.
[Ti] Título:Progress in the development of histamine H receptor antagonists/inverse agonists: a patent review (2013-2017).
[So] Source:Expert Opin Ther Pat;28(3):175-196, 2018 Mar.
[Is] ISSN:1744-7674
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Since years, ligands blocking histamine H receptor (H R) activity (antagonists/inverse agonists) are interesting targets in the search for new cures for CNS disorders. Intensive works done by academic and pharmaceutical company researchers have led to many potent and selective H R antagonists/inverse agonists. Some of them have reached to clinical trials. Areas covered: Patent applications from January 2013 to September 2017 and the most important topics connected with H R field are analysed. Espacenet, Patentscope, Pubmed, GoogleScholar or Cochrane Library online databases were principially used to collect all the materials. Expert opinion: The research interest in histamine H R field is still high although the number of patent applications has decreased during the past 4 years (around 20 publications). Complexity of histamine H R biology e.g. many isoforms, constitutive activity, heteromerization with other receptors (dopamine D , D , adenosine A ) and pharmacology make not easy realization and evaluation of therapeutic potential of anti-H R ligands. First results from clinical trials have verified potential utility of histamine H R antagonist/inverse agonists in some diseases. However, more studies are necessary for better understanding of an involvement of the histaminergic system in CNS-related disorders and helping more ligands approach to clinical trials and the market. Lists of abbreviations: hAChEI - human acetylcholinesterase inhibitor; hBuChEI - human butyrylcholinesterase inhibitor; hMAO - human monoamine oxidase; MAO - monoamine oxidase.
[Mh] Termos MeSH primário: Desenho de Drogas
Agonismo Inverso de Drogas
Antagonistas dos Receptores Histamínicos H3/farmacologia
[Mh] Termos MeSH secundário: Animais
Doenças do Sistema Nervoso Central/tratamento farmacológico
Doenças do Sistema Nervoso Central/fisiopatologia
Seres Humanos
Ligantes
Patentes como Assunto
Receptores Histamínicos H3/efeitos dos fármacos
Receptores Histamínicos H3/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Histamine H3 Antagonists); 0 (Ligands); 0 (Receptors, Histamine H3)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180215
[Lr] Data última revisão:
180215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180117
[St] Status:MEDLINE
[do] DOI:10.1080/13543776.2018.1424135


  2 / 261 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28888822
[Au] Autor:Ledneczki I; Tapolcsányi P; Gábor E; Éles J; Greiner I; Schmidt É; Némethy Z; Kedves RS; Balázs O; Román V; Lévay G; Mahó S
[Ad] Endereço:Chemical Works of Gedeon Richter Plc, H-1475, Budapest P.O. Box 27, Hungary. Electronic address: ledneczki@richter.hu.
[Ti] Título:Discovery of novel steroidal histamine H receptor antagonists/inverse agonists.
[So] Source:Bioorg Med Chem Lett;27(19):4525-4530, 2017 10 01.
[Is] ISSN:1464-3405
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Emerging from an HTS campaign, novel steroid-based histamine H receptor antagonists were identified and characterized. Structural moieties of the hit compounds were combined to improve binding affinities which resulted in compound 4 as lead molecule. During the lead optimization due to the versatile modifications of diamino steroid derivatives, several in vitro potent compounds with subnanomolar binding affinities to histamine H receptors were found. The unfavorable binding to rat muscarinic receptors was successfully reduced by tuning the basicity. Compound 20 showed significant in vivo activity in the rat dipsogenia model and could serve as a pharmacological tool in the future.
[Mh] Termos MeSH primário: Descoberta de Drogas
Agonistas dos Receptores Histamínicos/farmacologia
Antagonistas dos Receptores Histamínicos H3/farmacologia
Receptores Histamínicos H3/metabolismo
[Mh] Termos MeSH secundário: Animais
Relação Dose-Resposta a Droga
Agonistas dos Receptores Histamínicos/síntese química
Agonistas dos Receptores Histamínicos/química
Antagonistas dos Receptores Histamínicos H3/síntese química
Antagonistas dos Receptores Histamínicos H3/química
Seres Humanos
Estrutura Molecular
Ratos
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Histamine Agonists); 0 (Histamine H3 Antagonists); 0 (Receptors, Histamine H3)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171125
[Lr] Data última revisão:
171125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170911
[St] Status:MEDLINE


  3 / 261 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28726523
[Au] Autor:de Biase S; Nilo A; Gigli GL; Valente M
[Ad] Endereço:a Neurology Unit, Department of Experimental and Clinical Medical Sciences , University of Udine Medical School , Udine , Italy.
[Ti] Título:Investigational therapies for the treatment of narcolepsy.
[So] Source:Expert Opin Investig Drugs;26(8):953-963, 2017 Aug.
[Is] ISSN:1744-7658
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Narcolepsy is a chronic sleep disorder characterized by a pentad of excessive daytime sleepiness (EDS), cataplexy, sleep paralysis, hypnagogic/hypnopompic hallucinations, and disturbed nocturnal sleep. While non-pharmacological treatments are sometimes helpful, more than 90% of narcoleptic patients require a pharmacological treatment. Areas covered: The present review is based on an extensive Internet and PubMed search from 1994 to 2017. It is focused on drugs currently in development for the treatment of narcolepsy. Expert opinion: Currently there is no cure for narcolepsy, with treatment focusing on symptoms control. However, these symptomatic treatments are often unsatisfactory. The research is leading to a better understanding of narcolepsy and its symptoms. New classes of compounds with possible applications in the development of novel stimulant/anticataplectic medications are described. H3 receptor antagonists represent a new therapeutic option for EDS in narcolepsy. JZP-110, with its distinct mechanism of action, would be a new therapeutic option for the treatment of EDS in the coming years. In the future, hypocretin-based therapies and immune-based therapies, could modify the clinical course of the disease. However, more information would be necessary to completely understand the autoimmune process and also how this process can be altered for therapeutic benefits.
[Mh] Termos MeSH primário: Desenho de Drogas
Drogas em Investigação/uso terapêutico
Narcolepsia/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Distúrbios do Sono por Sonolência Excessiva/tratamento farmacológico
Distúrbios do Sono por Sonolência Excessiva/fisiopatologia
Drogas em Investigação/farmacologia
Antagonistas dos Receptores Histamínicos H3/farmacologia
Antagonistas dos Receptores Histamínicos H3/uso terapêutico
Seres Humanos
Narcolepsia/fisiopatologia
Orexinas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Drugs, Investigational); 0 (Histamine H3 Antagonists); 0 (Orexins)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170807
[Lr] Data última revisão:
170807
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170721
[St] Status:MEDLINE
[do] DOI:10.1080/13543784.2017.1356819


  4 / 261 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28501482
[Au] Autor:Mani V; Jaafar SM; Azahan NSM; Ramasamy K; Lim SM; Ming LC; Majeed ABA
[Ad] Endereço:Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), 42300 Bandar Puncak Alam, Selangor, Malaysia; Brain Degeneration and Therapeutics Group, Pharmaceutical & Life Sciences CoRe, Universiti Teknologi MARA (UiTM), 40450 Shah Alam, Selangor Darul Ehsan, Malaysia; Department of Pharmacology and T
[Ti] Título:Ciproxifan improves cholinergic transmission, attenuates neuroinflammation and oxidative stress but does not reduce amyloid level in transgenic mice.
[So] Source:Life Sci;180:23-35, 2017 Jul 01.
[Is] ISSN:1879-0631
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:AIM: The present study is aimed to investigate the ability of ciproxifan, a histamine H receptor antagonist to inhibit ß-amyloid (Aß)-induced neurotoxicity in SK-N-SH cells and APP transgenic mouse model. MATERIALS AND METHODS: In vitro studies was designed to evaluate the neuroprotective effects of ciproxifan in Aß - induced SK-N-SH cells. For the in vivo study, ciproxifan (1 and 3mg/kg, i.p.) was administrated to transgenic mice for 15days and behaviour was assessed using the radial arm maze (RAM). Brain tissues were collected to measure Aß levels (Aß and Aß ), acetylcholine (ACh), acetylcholinesterase (AChE), nitric oxide (NO), lipid peroxidation (LPO), antioxidant activities, cyclooxygenases (COX) and cytokines (IL-1α, IL-1ß and IL-6), while plasma was collected to measure TGF-1ß. RESULTS: The in vitro studies demonstrated neuroprotective effect of ciproxifan by increasing cell viability and inhibiting reactive oxygen species (ROS) in Aß -induced SK-N-SH cells. Ciproxifan significantly improved the behavioural parameters in RAM. Ciproxifan however, did not alter the Aß levels in APP transgenic mice. Ciproxifan increased ACh and showed anti-oxidant properties by reducing NO and LPO levels as well as enhancing antioxidant levels. The neuroinflammatory analysis showed that ciproxifan reduced both COX-1 and COX-2 activities, decreased the level of pro-inflammatory cytokines IL-1α, IL-1ß and IL-6 and increased the level of anti-inflammatory cytokine TGF-1ß. CONCLUSION: This present study provides scientific evidence of the use of ciproxifan via antioxidant and cholinergic pathways in the management of AD.
[Mh] Termos MeSH primário: Doença de Alzheimer/tratamento farmacológico
Antagonistas dos Receptores Histamínicos H3/farmacologia
Imidazóis/farmacologia
Fármacos Neuroprotetores/farmacologia
Estresse Oxidativo/efeitos dos fármacos
[Mh] Termos MeSH secundário: Acetilcolina/metabolismo
Doença de Alzheimer/patologia
Peptídeos beta-Amiloides/metabolismo
Animais
Antioxidantes/metabolismo
Linhagem Celular Tumoral
Citocinas/metabolismo
Modelos Animais de Doenças
Relação Dose-Resposta a Droga
Antagonistas dos Receptores Histamínicos H3/administração & dosagem
Seres Humanos
Imidazóis/administração & dosagem
Masculino
Aprendizagem em Labirinto/efeitos dos fármacos
Camundongos
Camundongos Transgênicos
Neuroblastoma/metabolismo
Fármacos Neuroprotetores/administração & dosagem
Fragmentos de Peptídeos/metabolismo
Espécies Reativas de Oxigênio/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amyloid beta-Peptides); 0 (Antioxidants); 0 (Cytokines); 0 (Histamine H3 Antagonists); 0 (Imidazoles); 0 (Neuroprotective Agents); 0 (Peptide Fragments); 0 (Reactive Oxygen Species); 0 (amyloid beta-protein (1-40)); 0 (amyloid beta-protein (1-42)); 0 (amyloid beta-protein (25-35)); 5EVQ7IRG99 (ciproxifan); N9YNS0M02X (Acetylcholine)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170515
[St] Status:MEDLINE


  5 / 261 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28372935
[Au] Autor:Kuder KJ; Lazewska D; Kaleta M; Latacz G; Kottke T; Olejarz A; Karcz T; Fruzinski A; Szczepanska K; Karolak-Wojciechowska J; Stark H; Kiec-Kononowicz K
[Ad] Endereço:Department of Technology and Biotechnology of Drugs, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, Kraków 30-688, Poland.
[Ti] Título:Synthesis and biological activity of novel tert-amylphenoxyalkyl (homo)piperidine derivatives as histamine H R ligands.
[So] Source:Bioorg Med Chem;25(10):2701-2712, 2017 May 15.
[Is] ISSN:1464-3391
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:As a continuation of our search for novel histamine H receptor ligands a series of twenty new tert-amyl phenoxyalkylamine derivatives (2-21) was synthesized. Compounds of four to eight carbon atoms spacer alkyl chain were evaluated on their binding properties at human histamine H receptor (hH R). The highest affinities were observed for pentyl derivatives 6-8 (K =8.8-23.4nM range) and among them piperidine derivative 6 with K =8.8nM. Structures 6, 7 were also classified as antagonists in cAMP accumulation assay (with EC =157 and 164nM, respectively). Moreover, new compounds were also evaluated for anticonvulsant activity in Antiepileptic Screening Program (ASP) at National Institute of Neurological Disorders and Stroke (USA). Seven compounds (2-4, 9, 11, 12 and 20) showed anticonvulsant activity at maximal electroshock (MES) test in the dose of 30mg/kg at 0.5h. In the subcutaneous pentetrazole (scMET) test compound 4 showed protection at 100 and 300mg/kg dose at mice, however compounds showed high neurotoxicity in rotarod test at used doses. Also, molecular modeling studies were undertaken, to explain affinity of compounds at hH R (taking into the consideration X-ray analysis of compound 18). In order to estimate "drug-likeness" of selected compounds in silico and experimental evaluation of lipophilicity, metabolic stability and cytotoxicity was performed.
[Mh] Termos MeSH primário: Anticonvulsivantes/síntese química
Antagonistas dos Receptores Histamínicos H3/síntese química
Piperidinas/química
Receptores Histamínicos H3/química
[Mh] Termos MeSH secundário: Animais
Anticonvulsivantes/metabolismo
Anticonvulsivantes/toxicidade
Sítios de Ligação
Linhagem Celular
Proliferação Celular/efeitos dos fármacos
Eletrochoque
Células HEK293
Antagonistas dos Receptores Histamínicos H3/metabolismo
Antagonistas dos Receptores Histamínicos H3/toxicidade
Seres Humanos
Masculino
Camundongos
Simulação de Acoplamento Molecular
Neurônios/efeitos dos fármacos
Piperidinas/metabolismo
Piperidinas/toxicidade
Ligação Proteica
Estrutura Terciária de Proteína
Ratos
Ratos Sprague-Dawley
Receptores Histamínicos H3/metabolismo
Solubilidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anticonvulsants); 0 (Histamine H3 Antagonists); 0 (Piperidines); 0 (Receptors, Histamine H3)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170426
[Lr] Data última revisão:
170426
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170405
[St] Status:MEDLINE


  6 / 261 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28132918
[Au] Autor:Lu CW; Lin TY; Chang CY; Huang SK; Wang SJ
[Ad] Endereço:Department of Anesthesiology, Far-Eastern Memorial Hospital, Pan-Chiao District, New Taipei City 22060, Taiwan; Department of Mechanical Engineering, Yuan Ze University, Taoyuan 320, Taiwan.
[Ti] Título:Ciproxifan, a histamine H receptor antagonist and inverse agonist, presynaptically inhibits glutamate release in rat hippocampus.
[So] Source:Toxicol Appl Pharmacol;319:12-21, 2017 Mar 15.
[Is] ISSN:1096-0333
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Ciproxifan is an H receptor antagonist and inverse agonist with antipsychotic effects in several preclinical models; its effect on glutamate release has been investigated in the rat hippocampus. In a synaptosomal preparation, ciproxifan reduced 4-aminopyridine (4-AP)-evoked Ca -dependent glutamate release and cytosolic Ca concentration elevation but did not affect the membrane potential. The inhibitory effect of ciproxifan on 4-AP-evoked glutamate release was prevented by the Gi/Go-protein inhibitor pertussis toxin and Ca 2.2 (N-type) and Ca 2.1 (P/Q-type) channel blocker ω-conotoxin MVIIC, but was not affected by the intracellular Ca -release inhibitors dantrolene and CGP37157. Furthermore, the phospholipase A (PLA ) inhibitor OBAA, prostaglandin E (PGE ), PGE2 subtype 2 (EP ) receptor antagonist PF04418948, and extracellular signal-regulated kinase (ERK) inhibitor FR180204 eliminated the inhibitory effect of ciproxifan on glutamate release. Ciproxifan reduced the 4-AP-evoked phosphorylation of ERK and synapsin I, a presynaptic target of ERK. The ciproxifan-mediated inhibition of glutamate release was prevented in synaptosomes from synapsin I-deficient mice. Moreover, ciproxifan reduced the frequency of miniature excitatory postsynaptic currents without affecting their amplitude in hippocampal slices. Our data suggest that ciproxifan, acting through the blockade of Gi/Go protein-coupled H receptors present on hippocampal nerve terminals, reduces voltage-dependent Ca entry by diminishing PLA /PGE /EP receptor pathway, which subsequently suppresses the ERK/synapsin I cascade to decrease the evoked glutamate release.
[Mh] Termos MeSH primário: Agonismo Inverso de Drogas
Ácido Glutâmico/secreção
Hipocampo/secreção
Antagonistas dos Receptores Histamínicos H3/farmacologia
Imidazóis/farmacologia
Terminações Pré-Sinápticas/secreção
[Mh] Termos MeSH secundário: Animais
Canais de Cálcio Tipo N/secreção
Relação Dose-Resposta a Droga
Hipocampo/efeitos dos fármacos
Masculino
Camundongos
Camundongos da Linhagem 129
Camundongos Endogâmicos C57BL
Técnicas de Cultura de Órgãos
Terminações Pré-Sinápticas/efeitos dos fármacos
Ratos
Ratos Sprague-Dawley
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Calcium Channels, N-Type); 0 (Histamine H3 Antagonists); 0 (Imidazoles); 0 (voltage-dependent calcium channel (P-Q type)); 3KX376GY7L (Glutamic Acid); 5EVQ7IRG99 (ciproxifan)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170131
[St] Status:MEDLINE


  7 / 261 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28129985
[Au] Autor:Szakacs Z; Dauvilliers Y; Mikhaylov V; Poverennova I; Krylov S; Jankovic S; Sonka K; Lehert P; Lecomte I; Lecomte JM; Schwartz JC; HARMONY-CTP study group
[Ad] Endereço:State Health Center, Budapest, Hungary.
[Ti] Título:Safety and efficacy of pitolisant on cataplexy in patients with narcolepsy: a randomised, double-blind, placebo-controlled trial.
[So] Source:Lancet Neurol;16(3):200-207, 2017 03.
[Is] ISSN:1474-4465
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Histaminergic neurons are crucial to maintain wakefulness, but their role in cataplexy is unknown. We assessed the safety and efficacy of pitolisant, a histamine H3 receptor inverse agonist, for treatment of cataplexy in patients with narcolepsy. METHODS: For this randomised, double-blind, placebo-controlled trial we recruited patients with narcolepsy from 16 sleep centres in nine countries (Bulgaria, Czech Republic, Hungary, Macedonia, Poland, Russia, Serbia, Turkey, and Ukraine). Patients were eligible if they were aged 18 years or older, diagnosed with narcolepsy with cataplexy according to version two of the International Classification of Sleep Disorders criteria, experienced at least three cataplexies per week, and had excessive daytime sleepiness (defined as an Epworth Sleepiness Scale score ≥12). We used a computer-generated sequence via an interactive web response system to randomly assign patients to receive either pitolisant or placebo once per day (1:1 ratio). Randomisation was done in blocks of four. Participants and investigators were masked to treatment allocation. Treatment lasted for 7 weeks: 3 weeks of flexible dosing decided by investigators according to efficacy and tolerance (5 mg, 10 mg, or 20 mg oral pitolisant), followed by 4 weeks of stable dosing (5 mg, 10 mg, 20 mg, or 40 mg). The primary endpoint was the change in the average number of cataplexy attacks per week as recorded in patient diaries (weekly cataplexy rate [WCR]) between the 2 weeks of baseline and the 4 weeks of stable dosing period. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01800045. FINDINGS: The trial was done between April 19, 2013, and Jan 28, 2015. We screened 117 patients, 106 of whom were randomly assigned to treatment (54 to pitolisant and 52 to placebo) and, after dropout, 54 patients from the pitolisant group and 51 from the placebo group were included in the intention-to-treat analysis. The WCR during the stable dosing period compared with baseline was decreased by 75% (WCR =2·27; WCR =9·15; WCR =0·25) in patients who received pitolisant and 38% (WCR =4·52; WCR =7·31; WCR =0·62) in patients who received placebo (rate ratio 0·512; 95% CI 0·43-0·60, p<0·0001). Treatment-related adverse events were significantly more common in the pitolisant group than in the placebo group (15 [28%] of 54 vs 6 [12%] of 51; p=0·048). There were no serious adverse events, but one case of severe nausea in the pitolisant group. The most frequent adverse events in the pitolisant group (headache, irritability, anxiety, and nausea) were mild or moderate except one case of severe nausea. No withdrawal syndrome was detected following pitolisant treatment; one case was detected in the placebo group. INTERPRETATION: Pitolisant was well tolerated and efficacious in reducing cataplexy. If confirmed in long-term studies, pitolisant might constitute a useful first-line therapy for cataplexy in patients with narcolepsy, for whom there are currently few therapeutic options. FUNDING: Bioprojet, France.
[Mh] Termos MeSH primário: Cataplexia/tratamento farmacológico
Cataplexia/etiologia
Antagonistas dos Receptores Histamínicos H3/uso terapêutico
Narcolepsia/complicações
Piperidinas/uso terapêutico
Resultado do Tratamento
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Bases de Dados Bibliográficas/estatística & dados numéricos
Método Duplo-Cego
Feminino
Seguimentos
Seres Humanos
Masculino
Meia-Idade
Estudos Retrospectivos
Índice de Gravidade de Doença
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Histamine H3 Antagonists); 0 (Piperidines); 4BC83L4PIY (1-(3-(3-(4-chlorophenyl)propoxy)propyl)piperidine)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170727
[Lr] Data última revisão:
170727
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170129
[St] Status:MEDLINE


  8 / 261 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28087755
[Ti] Título:â–¼Pitolisant for narcolepsy.
[So] Source:Drug Ther Bull;55(1):6-8, 2017 Jan.
[Is] ISSN:1755-5248
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:â–¼Pitolisant (Wakix-Bioprojet Pharma) is a new treatment for adults with narcolepsy with or without cataplexy. It was licensed for use in the EU in March last year and has orphan drug status. Here, we consider the evidence for pitolisant for the treatment of narcolepsy in adults and how it fits with current management strategies.
[Mh] Termos MeSH primário: Narcolepsia/tratamento farmacológico
Piperidinas/uso terapêutico
[Mh] Termos MeSH secundário: Adulto
Contraindicações
Gerenciamento Clínico
Antagonistas dos Receptores Histamínicos H3/uso terapêutico
Seres Humanos
Piperidinas/efeitos adversos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Histamine H3 Antagonists); 0 (Piperidines); 4BC83L4PIY (1-(3-(3-(4-chlorophenyl)propoxy)propyl)piperidine)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170115
[St] Status:MEDLINE
[do] DOI:10.1136/dtb.2017.1.0448


  9 / 261 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27353353
[Au] Autor:Sawant-Basak A; Chen L; Shaffer CL; Palumbo D; Schmidt A; Tseng E; Spracklin DK; Gallezot JD; Labaree D; Nabulsi N; Huang Y; Carson RE; McCarthy T
[Ad] Endereço:a Departments of Pharmacokinetics , Dynamics, and Metabolism, Pfizer Inc. , Cambridge , MA , USA.
[Ti] Título:Quantitative projection of human brain penetration of the H antagonist PF-03654746 by integrating rat-derived brain partitioning and PET receptor occupancy.
[So] Source:Xenobiotica;47(2):119-126, 2017 Feb.
[Is] ISSN:1366-5928
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:1. Unbound brain drug concentration (C ), a valid surrogate of interstitial fluid drug concentration (C ), cannot be directly determined in humans, which limits accurately defining the human C :C of investigational molecules. 2. For the H R antagonist (1R,3R)-N-ethyl-3-fluoro-3-[3-fluoro-4-(pyrrolidin-1-lmethyl)phenyl]cyclobutane-1-carboxamide (PF-03654746), we interrogated C :C in humans and nonhuman primate (NHP). 3. In rat, PF-03654746 achieved net blood-brain barrier (BBB) equilibrium (C :C of 2.11). 4. In NHP and humans, the PET receptor occupancy-based C IC of PF-03654746 was 0.99 nM and 0.31 nM, respectively, which were 2.1- and 7.4-fold lower than its in vitro human H K (2.3 nM). 5. In an attempt to understand this higher-than-expected potency in humans and NHP, rat-derived C :C of PF-03654746 was integrated with C IC to identify unbound (neuro) potency of PF-03654746, nIC . 6. The nIC of PF-03654746 was 2.1 nM in NHP and 0.66 nM in human which better correlated (1.1- and 3.49-fold lower) with in vitro human H K (2.3 nM). 7. This correlation of the nIC and in vitro hH K suggested the translation of net BBB equilibrium of PF-03654746 from rat to NHP and humans, and confirmed the use of C as a reliable surrogate of C . 8. Thus, nIC quantitatively informed the human C :C of PF-03654746.
[Mh] Termos MeSH primário: Ciclobutanos/farmacocinética
Antagonistas dos Receptores Histamínicos H3/farmacocinética
Pirrolidinas/farmacocinética
[Mh] Termos MeSH secundário: Animais
Transporte Biológico
Barreira Hematoencefálica
Encéfalo
Seres Humanos
Ratos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cyclobutanes); 0 (Histamine H3 Antagonists); 0 (N-ethyl-3-fluoro-3-(3-fluoro-4-(pyrrolidinylmethyl)phenyl)cyclobutanecarboxamide); 0 (Pyrrolidines)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170621
[Lr] Data última revisão:
170621
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160630
[St] Status:MEDLINE
[do] DOI:10.3109/00498254.2016.1166531


  10 / 261 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
[PMID]:27932863
[Au] Autor:Sadek B; Saad A; Latacz G; Kuder K; Olejarz A; Karcz T; Stark H; Kiec-Kononowicz K
[Ad] Endereço:Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
[Ti] Título:Non-imidazole-based histamine H3 receptor antagonists with anticonvulsant activity in different seizure models in male adult rats.
[So] Source:Drug Des Devel Ther;10:3879-3898, 2016.
[Is] ISSN:1177-8881
[Cp] País de publicação:New Zealand
[La] Idioma:eng
[Ab] Resumo:A series of twelve novel non-imidazole-based ligands ( ) was developed and evaluated for its in vitro binding properties at the human histamine H3 receptor (hH3R). The novel ligands were investigated for their in vivo protective effects in different seizure models in male adult rats. Among the H3R ligands ( ) tested, ligand showed significant and dose-dependent reduction in the duration of tonic hind limb extension in maximal electroshock (MES)-induced seizure model subsequent to acute systemic administration (5, 10, and 20 mg/kg, intraperitoneally), whereas ligands , , and without appreciable protection in MES model were most promising in pentylenetetrazole (PTZ) model. Moreover, the protective effect observed for ligand in MES model was lower than that observed for the reference drug phenytoin and was entirely abrogated when rats were co-administered with the brain-penetrant H1R antagonist pyrilamine (PYR) but not the brain-penetrant H2R antagonist zolantidine (ZOL), demonstrating that histaminergic neurotransmission by activation of postsynaptically located H1Rs seems to be involved in the protective action. On the contrary, PYR and ZOL failed to abrogate the full protection provided by in PTZ model and the moderate protective effect by in strychnine (STR) model. Moreover, the experimental and in silico estimation of properties such as metabolism was performed for five selected test compounds. Also, lipophilicity using planar reversed-phase thin-layer chromatography method was included for better understanding of the molecular properties of the tested compounds. Additionally, the absorption, distribution, metabolism, and elimination and toxicity parameters were evaluated for the most promising compounds , , , , and utilizing in vitro methods. These interesting results highlight the potential of H3R ligands as new antiepileptic drugs or as adjuvants to available epilepsy medications.
[Mh] Termos MeSH primário: Anticonvulsivantes/uso terapêutico
Modelos Animais de Doenças
Antagonistas dos Receptores Histamínicos H3/uso terapêutico
Éteres Fenílicos/uso terapêutico
Piperidinas/uso terapêutico
Receptores Histamínicos H3/metabolismo
Convulsões/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Anticonvulsivantes/química
Células HEK293
Antagonistas dos Receptores Histamínicos H3/administração & dosagem
Antagonistas dos Receptores Histamínicos H3/química
Seres Humanos
Injeções Intraperitoneais
Ligantes
Masculino
Éteres Fenílicos/administração & dosagem
Éteres Fenílicos/química
Piperidinas/administração & dosagem
Piperidinas/química
Ratos
Ratos Wistar
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (1-(3-(4-tert-pentylphenoxy)propyl)piperidine); 0 (Anticonvulsants); 0 (Histamine H3 Antagonists); 0 (Ligands); 0 (Phenyl Ethers); 0 (Piperidines); 0 (Receptors, Histamine H3); 4BC83L4PIY (1-(3-(3-(4-chlorophenyl)propoxy)propyl)piperidine)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170321
[Lr] Data última revisão:
170321
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161210
[St] Status:MEDLINE



página 1 de 27 ir para página                         
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

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