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[PMID]:29318278
[Au] Autor:Atri A; Frölich L; Ballard C; Tariot PN; Molinuevo JL; Boneva N; Windfeld K; Raket LL; Cummings JL
[Ad] Endereço:Ray Dolby Brain Health Center, California Pacific Medical Center, San Francisco.
[Ti] Título:Effect of Idalopirdine as Adjunct to Cholinesterase Inhibitors on Change in Cognition in Patients With Alzheimer Disease: Three Randomized Clinical Trials.
[So] Source:JAMA;319(2):130-142, 2018 01 09.
[Is] ISSN:1538-3598
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Importance: New therapeutic approaches for Alzheimer disease (AD) are needed. Objective: To assess whether idalopirdine, a selective 5-hydroxytryptamine-6 receptor antagonist, is effective for symptomatic treatment of mild to moderate AD. Design, Setting, and Participants: Three randomized clinical trials that included 2525 patients aged 50 years or older with mild to moderate AD (study 1: n = 933 patients at 119 sites; study 2: n = 858 at 158 sites; and study 3: n = 734 at 126 sites). The 24-week studies were conducted from October 2013 to January 2017; final follow-up on January 12, 2017. Interventions: Idalopirdine (10, 30, or 60 mg/d) or placebo added to cholinesterase inhibitor treatment (donepezil in studies 1 and 2; donepezil, rivastigmine, or galantamine in study 3). Main Outcomes and Measures: Primary end point in all 3 studies: change in cognition total score (range, 0-70; a lower score indicates less impairment) from baseline to 24 weeks measured by the 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog); key secondary end points: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Scale and 23-item Activities of Daily Living Inventory scores. Dose group efficacy required a significant benefit over placebo for the primary end point and 1 or more key secondary end points. Safety data and adverse event profiles were recorded. Results: Among 2525 patients randomized in the 3 trials (mean age, 74 years; mean baseline ADAS-Cog total score, 26; between 62% and 65% of participants were women), 2254 (89%) completed the studies. In study 1, the mean change in ADAS-Cog total score between baseline and 24 weeks was 0.37 for the 60-mg dose of idalopirdine group, 0.61 for the 30-mg dose group, and 0.41 for the placebo group (adjusted mean difference vs placebo, 0.05 [95% CI, -0.88 to 0.98] for the 60-mg dose group and 0.33 [95% CI, -0.59 to 1.26] for the 30-mg dose group). In study 2, the mean change in ADAS-Cog total score between baseline and 24 weeks was 1.01 for the 30-mg dose of idalopirdine group, 0.53 for the 10-mg dose group, and 0.56 for the placebo group (adjusted mean difference vs placebo, 0.63 [95% CI, -0.38 to 1.65] for the 30-mg dose group; given the gated testing strategy and the null findings at the 30-mg dose, statistical comparison of the 10-mg dose was not performed). In study 3, the mean change in ADAS-Cog total score between baseline and 24 weeks was 0.38 for the 60-mg dose of idalopirdine group and 0.82 for the placebo group (adjusted mean difference vs placebo, -0.55 [95% CI, -1.45 to 0.36]). Treatment-emergent adverse events occurred in between 55.4% and 69.7% of participants in the idalopirdine groups vs between 56.7% and 61.4% of participants in the placebo groups. Conclusions and Relevance: In patients with mild to moderate AD, the use of idalopirdine compared with placebo did not improve cognition over 24 weeks of treatment. These findings do not support the use of idalopirdine for the treatment of AD. Trial Registration: clinicaltrials.gov Identifiers: NCT01955161, NCT02006641, and NCT02006654.
[Mh] Termos MeSH primário: Doença de Alzheimer/tratamento farmacológico
Benzilaminas/uso terapêutico
Inibidores da Colinesterase/uso terapêutico
Indóis/uso terapêutico
Antagonistas da Serotonina/uso terapêutico
[Mh] Termos MeSH secundário: Acidentes por Quedas
Idoso
Idoso de 80 Anos ou mais
Doença de Alzheimer/psicologia
Benzilaminas/administração & dosagem
Benzilaminas/efeitos adversos
Inibidores da Colinesterase/efeitos adversos
Cognição/efeitos dos fármacos
Relação Dose-Resposta a Droga
Método Duplo-Cego
Quimioterapia Combinada
Feminino
Galantamina/uso terapêutico
Seres Humanos
Indanos/uso terapêutico
Indóis/administração & dosagem
Indóis/efeitos adversos
Masculino
Meia-Idade
Piperidinas/uso terapêutico
Rivastigmina/uso terapêutico
Antagonistas da Serotonina/administração & dosagem
Antagonistas da Serotonina/efeitos adversos
Falha de Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 ((2-(6-fluoro-1H-indol-3-yl)-ethyl)-(3-(2,2,3,3-tetrafluoropropoxy)benzyl)amine); 0 (Benzylamines); 0 (Cholinesterase Inhibitors); 0 (Indans); 0 (Indoles); 0 (Piperidines); 0 (Serotonin Antagonists); 0D3Q044KCA (Galantamine); 8SSC91326P (donepezil); PKI06M3IW0 (Rivastigmine)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180311
[Lr] Data última revisão:
180311
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180111
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1001/jama.2017.20373


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[PMID]:28837785
[Au] Autor:Arafa NMS; Ali EHA; Hassan MK
[Ad] Endereço:Faculty of Science, Biology Department, Jazan University, KSA & National Organization for Drug Control and Research, Department of Physiology, Egypt. Electronic address: nadianeuro@yahoo.com.
[Ti] Título:Canagliflozin prevents scopolamine-induced memory impairment in rats: Comparison with galantamine hydrobromide action.
[So] Source:Chem Biol Interact;277:195-203, 2017 Nov 01.
[Is] ISSN:1872-7786
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:Canagliflozin (CAN) is a sodium-glucose co-transporter 2 (SGLT2) inhibitor indicated to improve glycemic control in adults with type 2 diabetes mellitus. There is a little information about its effect on the cholinergic system that proposed mechanism for memory improvement occurring by SGLT2 drugs. This study aimed to estimate the effect of CAN as compared to galantamine (GAL) treatments for two weeks on scopolamine hydrobromide (SCO)-induced memory dysfunction in experimental rats. Animals divided into six groups; control (CON), CAN, GAL, SCO, SCO + CAN and SCO + GAL. Results indicated significant decrease in body weights of the CAN groups as compared to control values. Moreover, in the SCO + CAN and SCO + GAL the number of arm entry and number of correct alternation in Y maze task increased and showed improvement in the water maze task, acetylcholinesterase (AChE) activities decreased significantly, while monoamines levels significantly increased compared with the SCO group values. Results also recorded acetylcholine M1 receptor (M1 mAChR) in SCO + CAN or SCO + GAL groups in comparison with the SCO group. The study suggested that canagliflozin might improve memory dysfunction induced by scopolamine hydrobromide via cholinergic and monoamines system.
[Mh] Termos MeSH primário: Canagliflozina/uso terapêutico
Hipoglicemiantes/uso terapêutico
Transtornos da Memória/induzido quimicamente
Transtornos da Memória/prevenção & controle
Memória/efeitos dos fármacos
Hidrobrometo de Escopolamina
[Mh] Termos MeSH secundário: Acetilcolinesterase/metabolismo
Animais
Galantamina
Hipocampo/efeitos dos fármacos
Hipocampo/metabolismo
Masculino
Aprendizagem em Labirinto/efeitos dos fármacos
Transtornos da Memória/metabolismo
Ratos
Ratos Wistar
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Hypoglycemic Agents); 0D3Q044KCA (Galantamine); 0SAC974Z85 (Canagliflozin); 451IFR0GXB (Scopolamine Hydrobromide); EC 3.1.1.7 (Acetylcholinesterase)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171108
[Lr] Data última revisão:
171108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170825
[St] Status:MEDLINE


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[PMID]:28678552
[Au] Autor:Mohammad D; Chan P; Bradley J; Lanctôt K; Herrmann N
[Ad] Endereço:a Department of Pharmacology and Toxicology , University of Toronto , Toronto , ON , Canada.
[Ti] Título:Acetylcholinesterase inhibitors for treating dementia symptoms - a safety evaluation.
[So] Source:Expert Opin Drug Saf;16(9):1009-1019, 2017 Sep.
[Is] ISSN:1744-764X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: The prevalence of Alzheimer's disease (AD) continues to rise, while treatment options for cognitive impairment are limited. Acetylcholinesterase inhibitors (AChEIs) aim to provide symptomatic benefit for cognitive decline, however these drugs are not without adverse events (AEs). The safety profile of each drug must be taken carefully into consideration before being prescribed, as new dosages and formulations have recently been approved. Areas covered: Donepezil, galantamine and rivastigmine are the three AChEIs approved for the treatment of varying stages of AD. Numerous clinical trials and post-marketing studies have evaluated the safety of these medications. This article will review the safety, efficacy and tolerability of these drugs in treating AD. Topics including pharmacovigilance databases, concomitant drug interactions, prescribing cascades, and treatment discontinuation are also covered. Expert opinion: AChEI use in those with mild, moderate or severe AD provide modest improvements in cognition, function and behavior. The pharmacological treatment of AD using AChEIs is associated with generally mild AEs. Differences in drug formulations should be taken into account when determining the most appropriate route of administration for each individual. Furthermore, discontinuation of AChEIs must be carefully monitored as it may be associated with worsening cognitive impairment.
[Mh] Termos MeSH primário: Doença de Alzheimer/tratamento farmacológico
Inibidores da Colinesterase/uso terapêutico
Demência/tratamento farmacológico
[Mh] Termos MeSH secundário: Doença de Alzheimer/fisiopatologia
Inibidores da Colinesterase/efeitos adversos
Transtornos Cognitivos/tratamento farmacológico
Transtornos Cognitivos/fisiopatologia
Demência/fisiopatologia
Interações Medicamentosas
Galantamina/efeitos adversos
Galantamina/uso terapêutico
Seres Humanos
Indanos/efeitos adversos
Indanos/uso terapêutico
Piperidinas/efeitos adversos
Piperidinas/uso terapêutico
Rivastigmina/efeitos adversos
Rivastigmina/uso terapêutico
Índice de Gravidade de Doença
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Cholinesterase Inhibitors); 0 (Indans); 0 (Piperidines); 0D3Q044KCA (Galantamine); 8SSC91326P (donepezil); PKI06M3IW0 (Rivastigmine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170904
[Lr] Data última revisão:
170904
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170706
[St] Status:MEDLINE
[do] DOI:10.1080/14740338.2017.1351540


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[PMID]:28441543
[Au] Autor:Sun S; Wei Y; Cao Y; Deng B
[Ad] Endereço:Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin 541004, China.
[Ti] Título:Simultaneous electrochemiluminescence determination of galanthamine, homolycorine, lycorenine, and tazettine in Lycoris radiata by capillary electrophoresis with ultrasonic-assisted extraction.
[So] Source:J Chromatogr B Analyt Technol Biomed Life Sci;1055-1056:15-19, 2017 Jun 15.
[Is] ISSN:1873-376X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:After ultrasonic-assisted extraction, four lycoris radiata alkaloids: galanthamine, homolycorine, lycorenine, and tazettine were determined by capillary electrophoresis electrochemiluminescence. Polyvinylpyrrolidone was added to the running buffer (RB) to obtain better resolution. Experimental conditions influencing the determination were examined, including the additives, detection potential, separation voltage, injection voltage and time, and RB pH and concentration. Under optimal experimental conditions, the baseline separation of the four alkaloids occurred within 16min. The proposed method displayed the following linear ranges (in ng/mL): galanthamine [60-5000], homolycorine [40-5000], lycorenine [5.0-1500], and tazettine [8.0-2500]. The detection limits in ng/mL, (S/N=3), were galanthamine [14], homolycorine [11], lycorenine [1.8], and tazettine [3.1]. Intra-day and inter-day RSDs for the four alkaloids of the six replicates were less than 2.7% and 3.1%, respectively. The recoveries in% were: tazettine [102.5], lycorenine [98.20], galanthamine [97.30], and homolycorine [98.33].
[Mh] Termos MeSH primário: Alcaloides de Amaryllidaceae/análise
Eletroforese Capilar/métodos
Galantamina/análise
Medições Luminescentes/métodos
Lycoris/química
[Mh] Termos MeSH secundário: Alcaloides de Amaryllidaceae/isolamento & purificação
Tampões (Química)
Eletroforese Capilar/economia
Galantamina/isolamento & purificação
Limite de Detecção
Medições Luminescentes/economia
Extratos Vegetais/química
Povidona/química
Sonicação/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amaryllidaceae Alkaloids); 0 (Buffers); 0 (Plant Extracts); 0D3Q044KCA (Galantamine); 477-19-0 (lycorenine); 477-20-3 (homolycorine); 76WEU12CSO (tazettine); FZ989GH94E (Povidone)
[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:170426
[St] Status:MEDLINE


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[PMID]:28374576
[Au] Autor:Stavrakov G; Philipova I; Zheleva-Dimitrova D; Valkova I; Salamanova E; Konstantinov S; Doytchinova I
[Ad] Endereço:Faculty of Pharmacy, Medical University of Sofia, Sofia, Bulgaria.
[Ti] Título:Docking-based design and synthesis of galantamine-camphane hybrids as inhibitors of acetylcholinesterase.
[So] Source:Chem Biol Drug Des;90(5):709-718, 2017 Nov.
[Is] ISSN:1747-0285
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Galantamine (GAL) as an acetylcholinesterase inhibitor (AChEI) is among the main drugs approved for the treatment of Alzheimer's disease. It fits perfectly into acetylcholinesterase (AChE) binding gorge, but it is too short to fill it. The amyloid beta (Aß) peptide binds in the peripheral anionic site (PAS) at the entrance of the binding gorge of AChE and initiates the formation of amyloid plaques. The blockade of PAS prevents from AChE-induced Aß aggregation. In this study, we describe the design of a series of galantamine-camphane hybrids as AChEIs. Camphane (CAM) is a bulky fragment that disposes well on the wide gorge entrance. The designed hybrids have linkers of different length. They were docked into AChE, and the highest scored compounds were synthesized and tested for AChE inhibitory activity. Some of the novel hybrids showed 191- and 369-fold better inhibition than GAL. The CAM fragment of the best binders fits in the same region, proximal to PAS, where the Ω-loop of Aß binds to AChE. The hybrids cross blood-brain barrier by passive diffusion and are non-neurotoxic at the inhibitory concentrations.
[Mh] Termos MeSH primário: Acetilcolinesterase/metabolismo
Inibidores da Colinesterase/química
Inibidores da Colinesterase/farmacologia
Galantamina/química
Galantamina/farmacologia
[Mh] Termos MeSH secundário: Acetilcolinesterase/química
Animais
Barreira Hematoencefálica/metabolismo
Bornanos/química
Bornanos/farmacocinética
Bornanos/farmacologia
Linhagem Celular
Inibidores da Colinesterase/farmacocinética
Electrophorus
Galantamina/farmacocinética
Seres Humanos
Camundongos
Simulação de Acoplamento Molecular
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bornanes); 0 (Cholinesterase Inhibitors); 0D3Q044KCA (Galantamine); 464-15-3 (camphane); EC 3.1.1.7 (Acetylcholinesterase)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171113
[Lr] Data última revisão:
171113
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170405
[St] Status:MEDLINE
[do] DOI:10.1111/cbdd.12991


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[PMID]:28295141
[Au] Autor:Campbell NL; Perkins AJ; Gao S; Skaar TC; Li L; Hendrie HC; Fowler N; Callahan CM; Boustani MA
[Ad] Endereço:Department of Pharmacy Practice, Purdue University School of Pharmacy, West Lafayette, Indiana.
[Ti] Título:Adherence and Tolerability of Alzheimer's Disease Medications: A Pragmatic Randomized Trial.
[So] Source:J Am Geriatr Soc;65(7):1497-1504, 2017 Jul.
[Is] ISSN:1532-5415
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/OBJECTIVES: Post-marketing comparative trials describe medication use patterns in diverse, real-world populations. Our objective was to determine if differences in rates of adherence and tolerability exist among new users to acetylcholinesterase inhibitors (AChEI's). DESIGN: Pragmatic randomized, open label comparative trial of AChEI's currently available in the United States. SETTING: Four memory care practices within four healthcare systems in the greater Indianapolis area. PARTICIPANTS: Eligibility criteria included older adults with a diagnosis of possible or probable Alzheimer's disease (AD) who were initiating treatment with an AChEI. Participants were required to have a caregiver to complete assessments, access to a telephone, and be able to understand English. Exclusion criteria consisted of a prior severe adverse event from AChEIs. INTERVENTION: Participants were randomized to one of three AChEIs in a 1:1:1 ratio and followed for 18 weeks. MEASUREMENTS: Caregiver-reported adherence, defined as taking or not taking study medication, and caregiver-reported adverse events, defined as the presence of an adverse event. RESULTS: 196 participants were included with 74.0% female, 30.6% African Americans, and 72.9% who completed at least twelfth grade. Discontinuation rates after 18 weeks were 38.8% for donepezil, 53.0% for galantamine, and 58.7% for rivastigmine (P = .063) in the intent to treat analysis. Adverse events and cost explained 73.1% and 25.4% of discontinuation. No participants discontinued donepezil due to cost. Adverse events were reported by 81.2% of all participants; no between-group differences in total adverse events were statistically significant. CONCLUSIONS: This pragmatic comparative trial showed high rates of adverse events and cost-related non-adherence with AChEIs. Interventions improving adherence and persistence to AChEIs may improve AD management. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01362686 (https://clinicaltrials.gov/ct2/show/NCT01362686).
[Mh] Termos MeSH primário: Doença de Alzheimer/tratamento farmacológico
Inibidores da Colinesterase/efeitos adversos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Doença de Alzheimer/etnologia
Custos de Medicamentos
Grupos Étnicos
Feminino
Galantamina/uso terapêutico
Seres Humanos
Indanos/uso terapêutico
Indiana
Masculino
Adesão à Medicação
Piperidinas/uso terapêutico
Rivastigmina/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; PRAGMATIC CLINICAL TRIAL
[Nm] Nome de substância:
0 (Cholinesterase Inhibitors); 0 (Indans); 0 (Piperidines); 0D3Q044KCA (Galantamine); 8SSC91326P (donepezil); PKI06M3IW0 (Rivastigmine)
[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:170316
[St] Status:MEDLINE
[do] DOI:10.1111/jgs.14827


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[PMID]:28138912
[Au] Autor:Fisher A; Carney G; Bassett K; Dormuth CR
[Ad] Endereço:Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, 2176 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada. anat.fisher@ti.ubc.ca.
[Ti] Título:Tolerability of Cholinesterase Inhibitors: A Population-Based Study of Persistence, Adherence, and Switching.
[So] Source:Drugs Aging;34(3):221-231, 2017 Mar.
[Is] ISSN:1179-1969
[Cp] País de publicação:New Zealand
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Cholinesterase inhibitors (ChEIs) are prescribed to dementia patients despite their poor tolerance. Low tolerability potentially reduces persistence and adherence, while inducing switching between medications. Comparisons of these utilization measures contribute to knowledge of the relative tolerability of these medications. AIM: The aim was to compare persistence, adherence, and switching between donepezil, galantamine, oral rivastigmine, and rivastigmine patch. METHODS: A population-based cohort study, using British Columbia claims data (2009-2013), assessed ChEI new users aged 40 and older. We conducted survival analysis to compare persistence and Poisson regression to estimate switching rates. Good adherence, defined as a medication possession ratio of ≥80%, was modeled using log-binomial regression. Analyses were adjusted using propensity scores. RESULTS: Patients on galantamine had longer mean persistence and better adherence compared with patients on donepezil, with a hazard ratio for discontinuation of 0.91 [95% confidence interval (CI) 0.87-0.96] and a relative risk for good adherence of 1.01 (95% CI 1.002-1.03). Rivastigmine was associated with the shortest mean persistence [3.6 months (95% CI 3.0-4.2) and 5.0 (95% CI 4.7-5.3) for oral and patch, respectively] and the highest mean switching rates. Comparing the two rivastigmine preparations, the patch was associated with decreased discontinuation compared with oral [hazard ratio 0.79 (95% CI 0.71-0.89)] and decreased switching [relative risk 0.63 (95% CI 0.46-0.87) during the first 6 months of treatment]. Paradoxically, the patch was also associated with poorer adherence [relative risk for good adherence 0.94 (95% CI 0.91-0.98)] than the oral formulation. CONCLUSIONS: Based on estimates of persistence, adherence, and switching, galantamine was the best tolerated ChEI and rivastigmine the least.
[Mh] Termos MeSH primário: Doença de Alzheimer/tratamento farmacológico
Inibidores da Colinesterase/uso terapêutico
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Tolerância a Medicamentos
Feminino
Galantamina/uso terapêutico
Seres Humanos
Indanos/uso terapêutico
Masculino
Adesão à Medicação
Piperidinas/uso terapêutico
Rivastigmina/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cholinesterase Inhibitors); 0 (Indans); 0 (Piperidines); 0D3Q044KCA (Galantamine); 8SSC91326P (donepezil); PKI06M3IW0 (Rivastigmine)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171114
[Lr] Data última revisão:
171114
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170201
[St] Status:MEDLINE
[do] DOI:10.1007/s40266-017-0438-x


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[PMID]:28127976
[Au] Autor:Pohanka M; Zakova J; Fusek J
[Ti] Título:Galantamine has impact on immunity in mice exposed to keyhole limpet hemocyanin.
[So] Source:Bratisl Lek Listy;118(1):9-12, 2017.
[Is] ISSN:0006-9248
[Cp] País de publicação:Slovakia
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: In this work, we hypothesized whether galantamine could interact with the cholinergic anti-inflammatory pathway and modulate immunity this way. BACKGROUND: Galantamine is a drug used for the therapy of Alzheimer disease. The drug inhibits enzyme acetylcholinesterase in the central nervous system, which causes better availability of neurotransmitter acetylcholine. METHODS: In the experiment, we immunized BALB/c laboratory mice by keyhole limpet hemocyanin (KLH) in combination with galantamine in a dose 0.02-0.5 mg/kg. The animals were sacrificed from 1 to 7 days after the substances applications and plasma was collected in order to examine immunochemical markers by enzyme-linked immunosorbent assay. RESULTS: We found significant drop in production of immunoglobulins and interleukin (IL) 4 level while IL2, IL4 and tumour necrosis factor α remained unaltered for the whole experiment. We infer that galantamine causes better availability of acetylcholine also in blood system, where the neurotransmitter interacts with nicotinic acetylcholine receptors on macrophages and initiates cholinergic anti-inflammatory pathway. CONCLUSIONS: In a conclusion, galantamine can cause lower efficacy of vaccination or immunity response to an infectious disease and the phenomenon should be taken into consideration in the current therapy (Tab. 1, Fig. 2, Ref. 24).
[Mh] Termos MeSH primário: Acetilcolinesterase/sangue
Doença de Alzheimer/imunologia
Anti-Inflamatórios/farmacologia
Inibidores da Colinesterase/sangue
Galantamina/farmacologia
Hemocianinas/farmacologia
[Mh] Termos MeSH secundário: Acetilcolina/sangue
Animais
Interações Medicamentosas
Ensaio de Imunoadsorção Enzimática
Feminino
Imunoglobulinas/sangue
Mediadores da Inflamação/sangue
Macrófagos/efeitos dos fármacos
Macrófagos/imunologia
Camundongos
Camundongos Endogâmicos BALB C
Receptores Nicotínicos/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents); 0 (Cholinesterase Inhibitors); 0 (Immunoglobulins); 0 (Inflammation Mediators); 0 (Receptors, Nicotinic); 0D3Q044KCA (Galantamine); 9013-72-3 (Hemocyanins); EC 3.1.1.7 (Acetylcholinesterase); FV4Y0JO2CX (keyhole-limpet hemocyanin); N9YNS0M02X (Acetylcholine)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170128
[St] Status:MEDLINE
[do] DOI:10.4149/BLL_2017_002


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[PMID]:27806662
[Au] Autor:de la Tremblaye PB; Bondi CO; Lajud N; Cheng JP; Radabaugh HL; Kline AE
[Ad] Endereço:1 Department of Physical Medicine and Rehabilitation, University of Pittsburgh , Pittsburgh, Pennsylvania.
[Ti] Título:Galantamine and Environmental Enrichment Enhance Cognitive Recovery after Experimental Traumatic Brain Injury But Do Not Confer Additional Benefits When Combined.
[So] Source:J Neurotrauma;34(8):1610-1622, 2017 Apr 15.
[Is] ISSN:1557-9042
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Environmental enrichment (EE) enhances cognition after traumatic brain injury (TBI). Galantamine (GAL) is an acetylcholinesterase inhibitor that also may promote benefits. Hence, the aims of this study were to assess the efficacy of GAL alone (standard [STD] housing) and in combination with EE in adult male rats after TBI. The hypothesis was that both therapies would confer motor, cognitive, and histological benefits when provided singly, but that their combination would be more efficacious. Anesthetized rats received a controlled cortical impact or sham injury, then were randomly assigned to receive GAL (1, 2, or 3 mg/kg; intraperitoneally [i.p.]) or saline vehicle (VEH; 1 mL/kg; i.p.) beginning 24 h after surgery and once daily for 21 days (experiment 1). Motor (beam-balance/walk) and cognitive (Morris water maze [MWM]) assessments were conducted on post-operative Days 1-5 and 14-19, respectively. Cortical lesion volumes were quantified on Day 21. Sham controls were better versus all TBI groups. No differences in motor function or lesion volumes were observed among the TBI groups (p > 0.05). In contrast, GAL (2 mg/kg) enhanced MWM performance versus VEH and GAL (1 and 3 mg/kg; p < 0.05). In experiment 2, GAL (2 mg/kg) or VEH was combined with EE and the data were compared with the STD-housed groups from experiment 1. EE alone enhanced motor performance over the VEH-treated and GAL-treated (2 mg/kg) STD-housed groups (p < 0.05). Moreover, both EE groups (VEH or GAL) facilitated spatial learning and reduced lesion size versus STD + VEH controls (p < 0.05). No additional benefits were observed with the combination paradigm, which does not support the hypothesis. Overall, the data demonstrate that EE and once daily GAL (2 mg/kg) promote cognitive recovery after TBI. Importantly, the combined therapies did not negatively affect outcome and thus this therapeutic protocol may have clinical utility.
[Mh] Termos MeSH primário: Lesões Encefálicas Traumáticas
Inibidores da Colinesterase/farmacologia
Disfunção Cognitiva
Galantamina/farmacologia
Aprendizagem em Labirinto/fisiologia
Reabilitação Neurológica/métodos
Desempenho Psicomotor/fisiologia
[Mh] Termos MeSH secundário: Animais
Comportamento Animal/fisiologia
Lesões Encefálicas Traumáticas/complicações
Lesões Encefálicas Traumáticas/patologia
Lesões Encefálicas Traumáticas/fisiopatologia
Lesões Encefálicas Traumáticas/terapia
Inibidores da Colinesterase/administração & dosagem
Disfunção Cognitiva/tratamento farmacológico
Disfunção Cognitiva/etiologia
Disfunção Cognitiva/reabilitação
Terapia Combinada
Modelos Animais de Doenças
Meio Ambiente
Galantamina/administração & dosagem
Masculino
Ratos
Ratos Sprague-Dawley
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cholinesterase Inhibitors); 0D3Q044KCA (Galantamine)
[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:161104
[St] Status:MEDLINE
[do] DOI:10.1089/neu.2016.4790


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[PMID]:27846868
[Au] Autor:Hager K; Baseman AS; Nye JS; Brashear HR; Han J; Sano M; Davis B; Richards HM
[Ad] Endereço:Clinic for Medicine of the Elderly, Hannover, Germany.
[Ti] Título:Effect of concomitant use of memantine on mortality and efficacy outcomes of galantamine-treated patients with Alzheimer's disease: post-hoc analysis of a randomized placebo-controlled study.
[So] Source:Alzheimers Res Ther;8(1):47, 2016 Nov 15.
[Is] ISSN:1758-9193
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: A large, prospective, 2-year, randomized study in patients with mild-to-moderate Alzheimer's disease or mixed dementia demonstrated reductions in mortality and cognitive/functional decline in galantamine-treated patients. A post-hoc analysis was conducted to study the effect of (the presence or absence of) concomitant memantine use on treatment outcome. METHODS: Randomized patients (N = 2045) were divided into subgroups based on memantine use. Analyses included demographic and clinical characteristics (age, nursing home placement, Mini-Mental State Examination (MMSE) and Disability Assessment for Dementia (DAD) scores) and mortality endpoints. RESULTS: Overall, 496 (24.3 %) patients were memantine users and were older (mean (SD), 74.0 (8.76) vs 72.8 (8.76), p = 0.008), with lower MMSE scores (18.2 (4.16) vs 19.2 (4.02), p < 0.0001) and DAD scores (58.0 (23.49) vs 62.5 (20.52), p < 0.0001) than nonusers. Mortality rates (per 100 patient-years) in memantine nonusers (n = 1549) were lower for galantamine (1.39) vs placebo-treated patients (4.15). In memantine users, mortality rates were similar for placebo-treated (4.49) and galantamine-treated patients (5.57). In memantine nonusers at 24 months, the decline in MMSE scores (effect size (95 % CI) 0.25 (0.14; 0.36)) and DAD scores (0.17 (0.06; 0.28)) from baseline was lower in galantamine patients vs placebo patients. The absence of these benefits in memantine users could not be explained by baseline age, MMSE, or DAD scores. CONCLUSION: This post-hoc analysis shows that the beneficial effects of galantamine at 2 years post treatment were not observed in patients who had been placed on background memantine. The reasons for memantine treatment and the possibility of interaction between memantine and galantamine merit further investigation. TRIAL REGISTRATION: ClinicalTrials.gov NCT00679627 . Registered 15 May 2008.
[Mh] Termos MeSH primário: Doença de Alzheimer
Inibidores da Colinesterase/uso terapêutico
Antagonistas de Aminoácidos Excitatórios/uso terapêutico
Galantamina/uso terapêutico
Memantina/uso terapêutico
Resultado do Tratamento
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Doença de Alzheimer/tratamento farmacológico
Doença de Alzheimer/mortalidade
Doença de Alzheimer/psicologia
Avaliação da Deficiência
Método Duplo-Cego
Feminino
Seres Humanos
Estudos Longitudinais
Masculino
Meia-Idade
Escalas de Graduação Psiquiátrica
Estudos Retrospectivos
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Cholinesterase Inhibitors); 0 (Excitatory Amino Acid Antagonists); 0D3Q044KCA (Galantamine); W8O17SJF3T (Memantine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171013
[Lr] Data última revisão:
171013
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161117
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE



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