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1.
Medicine (Baltimore) ; 99(11): e19527, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32176105

RESUMO

OBJECTIVE: Cognitive enhancers, including cholinesterase inhibitors and memantine, are used to treat dementia, but their effect for reducing post-electroconvulsive therapy (post-ECT) cognitive side effects is unclear. We conducted a systematic review and meta-analysis to assess the effectiveness of cognitive enhancers in the prevention of cognitive side effects due to ECT. METHODS: We identified relevant studies by searching electronic databases (e.g., PubMed, EMBASE, Web of Science, Cochrane Library). Only studies published up to October 2019 comparing cognitive enhancer vs placebo for cognitive function after ECT were included. The primary outcome extracted from the studies was cognitive function score. RESULTS: Five studies with 202 patients were included in this study. The cognitive enhancer group (CEG) had a significantly higher cognitive function score. Moreover, sensitivity analysis showed that no individual study had a significant impact on the overall results. CONCLUSIONS: This meta-analysis revealed that cognitive enhancers might improve cognitive function and reduce ECT-induced cognitive side effects. Nevertheless, more high-quality randomized controlled trials (RCTs) with long-term follow-up are still needed to make the final conclusion.


Assuntos
Transtornos Cognitivos/prevenção & controle , Cognição , Transtorno Depressivo/terapia , Eletroconvulsoterapia/efeitos adversos , Nootrópicos/administração & dosagem , Humanos , Período Pré-Operatório , Substâncias Protetoras/administração & dosagem
2.
J Biochem Mol Toxicol ; 34(2): e22429, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31860774

RESUMO

Alzheimer's disease (AD) is an age-associated neurodegenerative disease, which is developed by oxidative stress and acetylcholine contraction in the synaptic cleft of the neurons. This leads to dementia, memory loss, and decrease in learning ability and orientation. In this research work, we aimed to explore the neuroprotective effect of neferine on AlCl3 -induced AD in rats. The results of our study revealed that the increased reactive oxygen species (ROS) and nitric oxide in the hippocampus leads to the development of AD in the rats. The oral treatment of neferine done the following occurrences such as; it potentially inhibited the ROS formation and acts as a scavenging molecule by preventing the neurodegeneration. It also improved the memory and learning ability to complete the maze activity in the AD rats and significantly increased the antioxidants superoxide dismutase, catalase, and reduced glutathione in neferine treated AD rats. It aggressively declined the activity of acetylcholine esterase and Na+ K+ ATPase in the neurodegenerative rat models. The gene expression pattern of neuroinflammatory cytokines such as tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) were decreased in the neferine-treated rats. The neuroinflammatory proteins such as inducible nitric oxide (iNOS), cyclooxygenase-2 (COX-2), and nuclear factor kappa ß (Nf-κß) were decreased and Nf-κß inhibitor IKBα was increased in the neferine-treated AD rats. Finally, the histology study proved that the neferine treatment possibly prevents neurodegeneration in the hippocampus tissue of the AD models. Hence, these all findings concluded that the neferine could be a potential neuropreventive as well as neurodegenerative therapeutic compound in neurological and cognitive dysfunction.


Assuntos
Cloreto de Alumínio/farmacologia , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/tratamento farmacológico , Benzilisoquinolinas/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Fármacos Neuroprotetores/farmacologia , Nootrópicos/farmacologia , Administração Oral , Cloreto de Alumínio/efeitos adversos , Animais , Comportamento Animal/efeitos dos fármacos , Benzilisoquinolinas/administração & dosagem , Ciclo-Oxigenase 2/metabolismo , Citocinas/genética , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/administração & dosagem , Feminino , Expressão Gênica/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , NF-kappa B/metabolismo , Fármacos Neuroprotetores/administração & dosagem , Óxido Nítrico Sintase Tipo II/metabolismo , Nootrópicos/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar
3.
Rom J Ophthalmol ; 63(3): 222-230, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31687623

RESUMO

Objectives. Neuroprotective treatment, including citicoline, is a new perspective in glaucoma management, having the role of progression delay. The purpose of the present study was to observe the evolution of the different parameters in patients with glaucoma treated with citicoline. Methods. 22 patients with GPUD were enrolled in the study, and they received oral citicoline in addition to the ocular hypotensive therapy. Investigations were performed at the beginning of the current study, then at 3 months and 6 months, and included, besides full ophthalmologic checkup and IOP determination, optic nerve and RGCs OCT, and visual evoked potentials, pattern and flash. The data we obtained were statistically analyzed with the SPSS (Microsoft) program. Results. The outcomes of the study following VEP wave analysis indicated variations in P100 wave amplitude, but after 6 months period, an increase was found. Also, the P2 wave amplitude recorded statistically insignificant variations. The increase in P2 latency at 6 months was noted as statistically significant. Negative correlations were also met between the thickness of the RGC layer and the P100 latency, but also between the amplitude and the latency of this wave. At 6 months, a positive correlation between the RGC layer and the P100 amplitude was observed. The RNFL thickness at the optical disc had higher values at the 6 months visit, it was statistically significant, and a slight increase in the thickness of the RGC layer between successive visits was noted. These might be an examination artifact because clinically they are not possible. The RNFL thickness showed a positive correlation with the amplitude of P100 and P2 waves. Conclusions. The study of the parameters and their correlations demonstrated that citicoline had positive effects in glaucoma on certain aspects, data confirmed by literature.


Assuntos
Citidina Difosfato Colina/administração & dosagem , Glaucoma de Ângulo Aberto/tratamento farmacológico , Doenças do Nervo Óptico/prevenção & controle , Nervo Óptico/diagnóstico por imagem , Células Ganglionares da Retina/patologia , Administração Oral , Adolescente , Adulto , Idoso , Progressão da Doença , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Glaucoma de Ângulo Aberto/complicações , Glaucoma de Ângulo Aberto/diagnóstico , Humanos , Pressão Intraocular/fisiologia , Masculino , Pessoa de Meia-Idade , Nootrópicos/administração & dosagem , Doenças do Nervo Óptico/diagnóstico , Doenças do Nervo Óptico/etiologia , Estudos Prospectivos , Células Ganglionares da Retina/efeitos dos fármacos , Fatores de Tempo , Tomografia de Coerência Óptica , Resultado do Tratamento , Adulto Jovem
4.
Einstein (Sao Paulo) ; 18: eAO4745, 2019.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31664322

RESUMO

OBJECTIVE: To estimate the prevalence of and factors associated with the use of methylphenidate for cognitive enhancement among undergraduate students. METHODS: Simple random sample of students of the Universidade Federal de Minas Gerais (n=438), invited to answer an online questionnaire about the use of methylphenidate. Data collection occurred from September 2014 to January 2015. The sample was described by means of proportions, means and standard deviations. A multivariate analysis was performed using the Classification and Regression Tree algorithm to classify the cases of use of methylphenidate for cognitive enhancement in groups, based on the exposure variables. RESULTS: Out of 378 students included, 5.8% (n=22) reported using methylphenidate for cognitive enhancement; in that, 41% (9/22) in the 4 weeks prior to the survey. The housing situation was the variable most often associated with the use of methylphenidate for cognitive enhancement. Eleven students reported using methylphenidate for cognitive enhancement and other purposes 4 weeks prior to the survey, 27% of whom had no medical prescription to purchase it. CONCLUSION: The use of methylphenidate for cognitive enhancement is frequent among Brazilian undergraduate students and should be considered a serious public health problem, especially due to risks of harm and adverse effects associated with its use.


Assuntos
Estimulantes do Sistema Nervoso Central/administração & dosagem , Nootrópicos/administração & dosagem , Nootrópicos/uso terapêutico , Estudantes/estatística & dados numéricos , Universidades/estatística & dados numéricos , Adulto , Brasil/epidemiologia , Estudos Transversais , Árvores de Decisões , Exercício/psicologia , Feminino , Humanos , Masculino , Metilfenidato/administração & dosagem , Uso Off-Label/estatística & dados numéricos , Prevalência , Características de Residência/estatística & dados numéricos , Fatores de Risco , Fatores Socioeconômicos , Estudantes/psicologia , Inquéritos e Questionários , Adulto Jovem
5.
Medicine (Baltimore) ; 98(34): e16920, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31441874

RESUMO

RATIONALE: Vascular cognitive impairment (VCI) is a common cause of dementia. Research suggests that hereditary factors (gene mutations) play an important role in the pathogenesis of VCI, and a mutation of the NOTCH3 locus is frequently identified in affected patients. Herein, we report the case of a patient with confirmed VCI associated with a NOTCH3 exon 33 gene mutation and review the relevant VCI literature. PATIENT CONCERNS: A 48-year-old man presented to our neurology clinic with gradually progressive cognitive impairment. DIAGNOSES: Brain magnetic resonance imaging revealed multiple punctate hyperintensities in the patient's periventricular white matter. Genetic analysis showed a c.6744C > T, p. Ala2223Val substitution in exon 33 of the NOTCH3 gene. We diagnosed thepatient with VCI secondary to a NOTCH3 gene mutation. INTERVENTIONS: Donepezil (5 mg) and memantine (5 mg) daily. OUTCOMES: The patient showed symptom improvement at his 3-month and 6-month follow-up appointments. LESSONS: This patient may have a new type of mutation that is different from the one seen in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, although it involves a NOTCH3 defect. We propose that the entire NOTCH3 gene should be sequenced in patients with suspected hereditary VCI. This practice could facilitate the discovery of newpathogenic mutations and diseases.


Assuntos
Demência Vascular/genética , Receptor Notch3 , Disfunção Cognitiva/etiologia , Demência Vascular/complicações , Demência Vascular/tratamento farmacológico , Donepezila/administração & dosagem , Humanos , Masculino , Memantina/administração & dosagem , Pessoa de Meia-Idade , Mutação , Nootrópicos/administração & dosagem , Substância Branca/diagnóstico por imagem , Substância Branca/patologia
6.
J Clin Psychopharmacol ; 39(5): 455-461, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31433334

RESUMO

BACKGROUND: Animal models and human studies have identified the potential of modafinil as a cognitive enhancing agent, independent of its effects on promoting wakefulness in sleep-deprived samples. Given that single-dose applications of other putative memory enhancers (eg, D-cycloserine, yohimbine, and methylene blue) have shown success in enhancing clinical outcomes for anxiety-related disorders, we conducted a meta-analytic review examining the potential for single-dose effects for modafinil on cognitive functioning in non-sleep-deprived adults. METHODS: A total of 19 placebo-controlled trials that examined the effects of single-dose modafinil versus placebo on the cognitive domains of attention, executive functioning, memory, or processing speed were identified, allowing for the calculation of 67 cognitive domain-specific effect sizes. RESULTS: The overall positive effect of modafinil over placebo across all cognitive domains was small and significant (g = 0.10; 95% confidence interval, 0.05-0.15; P < 0.001). No significant differences between cognitive domains were found. Likewise, no significant moderation was found for modafinil dose (100 mg vs 200 mg) or for the populations studied (psychiatric vs nonpsychiatric). CONCLUSIONS: In conclusion, the available evidence indicates only limited potential for modafinil to act as a cognitive enhancer outside sleep-deprived populations.


Assuntos
Cognição/efeitos dos fármacos , Modafinila/administração & dosagem , Nootrópicos/administração & dosagem , Adulto , Atenção/efeitos dos fármacos , Estimulantes do Sistema Nervoso Central/administração & dosagem , Estimulantes do Sistema Nervoso Central/farmacologia , Função Executiva/efeitos dos fármacos , Humanos , Modafinila/farmacologia , Nootrópicos/farmacologia
7.
J Mol Neurosci ; 69(2): 224-234, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31230222

RESUMO

The safety and efficacy of a novel combination treatment of AChE inhibitors and choline supplement was initiated and evaluated in children and adolescents with autism spectrum disorder (ASD). Safety and efficacy were evaluated on 60 children and adolescents with ASD during a 9-month randomized, double-blind, placebo-controlled trial comprising 12 weeks of treatment preceded by baseline evaluation, and followed by 6 months of washout, with subsequent follow-up evaluations. The primary exploratory measure was language, and secondary measures included core autism symptoms, sleep and behavior. Significant improvement was found in receptive language skills 6 months after the end of treatment as compared to placebo. The percentage of gastrointestinal disturbance reported as a side effect during treatment was higher in the treatment group as compared to placebo. The treatment effect was enhanced in the younger subgroup (younger than 10 years), occurred already at the end of the treatment phase, and was sustained at 6 months post treatment. No significant side effects were found in the younger subgroup. In the adolescent subgroup, no significant improvement was found, and irritability was reported statistically more often in the adolescent subgroup as compared to placebo. Combined treatment of donepezil hydrochloride with choline supplement demonstrates a sustainable effect on receptive language skills in children with ASD for 6 months after treatment, with a more significant effect in those under the age of 10 years.


Assuntos
Transtorno Autístico/tratamento farmacológico , Colina/uso terapêutico , Donepezila/uso terapêutico , Linguagem , Nootrópicos/uso terapêutico , Adolescente , Criança , Colina/administração & dosagem , Colina/efeitos adversos , Donepezila/administração & dosagem , Donepezila/efeitos adversos , Quimioterapia Combinada , Feminino , Gastroenteropatias/etiologia , Humanos , Humor Irritável/efeitos dos fármacos , Masculino , Nootrópicos/administração & dosagem , Nootrópicos/efeitos adversos
8.
Medicine (Baltimore) ; 98(24): e16082, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31192971

RESUMO

BACKGROUND: In recent years, L-3-n-butylphthalide (L-NBP) has been used for Parkinson disease dementia (PDD) to attenuate cognitive impairments in China. Therefore, we selected published and qualified clinical trials to conduct a systematic review and meta-analysis with the aim of assessing the effectiveness and safety of L-NBP in the treatment of PDD. OBJECTIVE: This systematic review and meta-analysis aimed to assess the effectiveness and safety of L-NBP in the treatment of PDD. METHODS: We searched PubMed, EMBASE, China National Knowledge Infrastructure, Chinese Scientific Journal Database (VIP database), and Wan-Fang Database to collect eligible articles. We calculated pooled estimates of odds ratios or the standard mean deviation with 95% confidence intervals. RESULTS: Eight randomized controlled trials were included in our meta-analysis. Our meta-analysis showed that L-NBP combined with Western medicine (WM) had a better effect on improving cognitive dysfunction, the total effective rate, symptoms of Parkinson disease (PD), and activities of daily living function than WM alone. Regarding safety, no serious adverse events were observed in the experimental group. CONCLUSION: We found that L-NBP as a complementary therapy may have a positive therapeutic effect for improving cognitive dysfunction, the total effective rate, symptoms of PD, quality of life, and the related serum factors in the treatment of PDD. Furthermore, L-NBP was a safe treatment for PDD. However, the findings of our meta-analysis may be influenced by the low quality of the included studies. We highlight the need to conduct trials with higher methodological quality.


Assuntos
Antiparkinsonianos/administração & dosagem , Benzofuranos/administração & dosagem , Demência/tratamento farmacológico , Nootrópicos/administração & dosagem , Doença de Parkinson/tratamento farmacológico , Antiparkinsonianos/efeitos adversos , Benzofuranos/efeitos adversos , Cápsulas , Demência/etiologia , Humanos , Nootrópicos/efeitos adversos , Doença de Parkinson/psicologia , Ensaios Clínicos Controlados Aleatórios como Assunto
9.
Geriatr Gerontol Int ; 19(7): 654-659, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31074090

RESUMO

AIM: To evaluate the prevalence of potentially inappropriate prescribing (PIP), as defined by the internationally validated Screening Tool of Older Person's Prescriptions (STOPP) criteria, in 12 months before and after initiation of medicines for dementia. METHODS: A retrospective cohort study was carried out involving people with their first claim for dispensing of medicines for dementia (cholinesterase inhibitor or memantine) between 1 January 2015 and 31 December 2015, aged ≥65 years at 1 January 2016 and alive at the end of 2016. The index date was defined as the date of first supply of medicines for dementia. PIP was identified using the Screening Tool of Older Person's Prescriptions criteria, and PIP prevalence was compared in the 12 months pre- and post-index date. The McNemar's test was used to test differences in the prevalence of PIP between the two time periods. RESULTS: The cohort included 1176 patients: 60% were women and the median age was 80 years. The overall PIP prevalence was 85% in the 12 months pre-initiation of medicines for dementia compared with 89% in the 12 months post-initiation (P < 0.0001). The median number of Screening Tool of Older Person's Prescriptions criteria was two (interquartile range 1-4) in the 12 months pre-initiation of medicines for dementia, increasing to three (range 2-4) in the 12 months post-initiation. CONCLUSIONS: PIP was common in people dispensed medicines for dementia, with a significant increase in prevalence post-initiation of medicines for dementia compared with pre-initiation. These results highlight the need for targeted interventions to minimize inappropriate use of medicines in people with dementia. Geriatr Gerontol Int 2019; 19: 654-659.


Assuntos
Inibidores da Colinesterase , Demência/tratamento farmacológico , Prescrições de Medicamentos , Prescrição Inadequada/prevenção & controle , Memantina , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Austrália/epidemiologia , Inibidores da Colinesterase/administração & dosagem , Inibidores da Colinesterase/efeitos adversos , Demência/diagnóstico , Demência/epidemiologia , Demência/psicologia , Prescrições de Medicamentos/normas , Prescrições de Medicamentos/estatística & dados numéricos , Feminino , Humanos , Prescrição Inadequada/efeitos adversos , Masculino , Memantina/administração & dosagem , Memantina/efeitos adversos , Nootrópicos/administração & dosagem , Nootrópicos/efeitos adversos , Seleção de Pacientes , Lista de Medicamentos Potencialmente Inapropriados/normas , Prevalência , Estudos Retrospectivos
10.
eNeuro ; 6(2)2019.
Artigo em Inglês | MEDLINE | ID: mdl-31040160

RESUMO

Currently there is no effective therapy available for cognitive impairments in Down syndrome (DS), one of the most prevalent forms of intellectual disability in humans associated with the chromosomes 21 trisomy. Glucagon-like peptide-1 (GLP-1) is an incretin hormone that maintains glucose homeostasis by stimulating insulin secretion. Its natural cleavage product GLP-1 (9-36) lacks insulinotropic effects and has a low binding affinity for GLP-1 receptors; thus, GLP-1 (9-36) has historically been identified as an inactive metabolite. Conversely, recent work has demonstrated interesting physiological properties of GLP-1 (9-36) such as cardioprotection and neuroprotection. We have previously shown that GLP-1 (9-36) administration enhances neuronal plasticity in young WT mice and ameliorates cognitive deficits in a mouse model of Alzheimer's disease. Here, we report that systemic administration of GLP-1 (9-36) in Ts65Dn DS model mice of either sex resulted in decreased mitochondrial oxidative stress in hippocampus and improved dendritic spine morphology, increase of mature spines and reduction of immature spines. Importantly, these molecular alterations translated into functional changes in that long-term potentiation failure and cognitive impairments in TsDn65 DS model mice were rescued with GLP-1 (9-36) treatment. We also show that chronic GLP-1 (9-36) treatment did not alter glucose tolerance in either WT or DS model mice. Our findings suggest that GLP-1 (9-36) treatment may have therapeutic potential for DS and other neurodegenerative diseases associated with increased neuronal oxidative stress.


Assuntos
Aprendizagem da Esquiva/efeitos dos fármacos , Disfunção Cognitiva/tratamento farmacológico , Espinhas Dendríticas/efeitos dos fármacos , Síndrome de Down/tratamento farmacológico , Peptídeo 1 Semelhante ao Glucagon/análogos & derivados , Hipocampo/efeitos dos fármacos , Potenciação de Longa Duração/efeitos dos fármacos , Plasticidade Neuronal/efeitos dos fármacos , Nootrópicos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Memória Espacial/efeitos dos fármacos , Animais , Comportamento Animal/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Peptídeo 1 Semelhante ao Glucagon/administração & dosagem , Peptídeo 1 Semelhante ao Glucagon/farmacologia , Teste de Tolerância a Glucose , Masculino , Camundongos , Camundongos Transgênicos , Nootrópicos/administração & dosagem
11.
Prog Brain Res ; 245: 57-88, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30961872

RESUMO

The treatment of Alzheimer's disease (AD) is up to today one of the most unsuccessful examples of biomedical science. Despite the high number of literature evidences detailing the multifactorial and complex etiopathology of AD, no cure is yet present on the market and the available treatments are only symptomatic. The reasons could be ascribed on two main factors: (i) lack of ability of the majority of drugs to cross the blood-brain barrier (BBB), thus excluding the brain for any successful therapy; (ii) lack of selectivity and specificity of drugs, decreasing the efficacy of even potent anti-AD drugs. The exploitation of specifically engineered nanomedicines planned to cross the BBB and to target the most "hot" site of action (i.e., ß-amyloid) is one of the most interesting innovations in drug delivery and could reasonably represent an promising choice for possible treatments and even early-diagnosis of AD. In this chapter, we therefore outline the most talented approaches in AD treatment with a specific focus on the main advantages/drawbacks and future possible translation to clinic application.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/efeitos dos fármacos , Barreira Hematoencefálica , Nanomedicina/métodos , Fármacos Neuroprotetores/administração & dosagem , Nootrópicos/administração & dosagem , Animais , Humanos
12.
eNeuro ; 6(2)2019.
Artigo em Inglês | MEDLINE | ID: mdl-31016230

RESUMO

The importance of the dorsal hippocampus (DH) in mediating the memory-enhancing effects of the sex-steroid hormone 17ß-estradiol (E2) is well established. However, estrogen receptors (ERs) are highly expressed in other brain regions that support memory formation, including the medial prefrontal cortex (mPFC). The mPFC and DH interact to mediate the formation of several types of memory, and behavioral tasks that recruit the mPFC are enhanced by systemic E2 administration, making this region a prime candidate for investigating circuit-level questions regarding the estrogenic regulation of memory. Further, infusion of E2 directly into the DH increases dendritic spine density in both the DH and mPFC, and this effect depends upon rapid activation of cell-signaling pathways in the DH, demonstrating a previously unexplored interaction between the DH and mPFC that led us to question the role of the mPFC in object memory consolidation and the necessity of DH-mPFC interactions in the memory-enhancing effects of E2. Here, we found that infusion of E2 directly into the mPFC of ovariectomized mice increased mPFC apical spine density and facilitated object recognition and spatial memory consolidation, demonstrating that E2 in the mPFC increases spinogenesis and enhances on memory consolidation. Next, chemogenetic suppression of the mPFC blocked the beneficial effects of DH-infused E2 on memory consolidation, indicating that systems-level DH-mPFC interactions are necessary for the memory-enhancing effects of E2. Together, these studies provide evidence that E2 in the mPFC mediates memory formation, and reveal that the DH and mPFC act in concert to support the memory-enhancing effects of E2 in female mice.


Assuntos
Espinhas Dendríticas/efeitos dos fármacos , Estradiol/farmacologia , Estrogênios/farmacologia , Hipocampo/efeitos dos fármacos , Consolidação da Memória/efeitos dos fármacos , Nootrópicos/farmacologia , Córtex Pré-Frontal/efeitos dos fármacos , Memória Espacial/efeitos dos fármacos , Animais , Estradiol/administração & dosagem , Estrogênios/administração & dosagem , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Nootrópicos/administração & dosagem , Ovariectomia
13.
PLoS One ; 14(4): e0215612, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31002681

RESUMO

Understanding the effects of cognitive enhancing drugs is an important area of research. Much of the research, however, has focused on restoring memory following some sort of disruption to the brain, such as damage or injections of scopolamine. Aniracetam is a positive AMPA-receptor modulator that has shown promise for improving memory under conditions when the brain has been damaged, but its effectiveness in improving memory in neurologically healthy subjects is unclear. The aim of the present study was to examine the effects of aniracetam (100mg/kg and 200 mg/kg) on short-term memory in "neurologically healthy" pigeons. Pigeons were administered aniracetam via either intramuscular injection or orally, either 30 or 60 minutes prior to testing on a delayed matching-to-sample task. Aniracetam had no effect on the pigeons' memory performance, nor did it affect response latency. These findings add to the growing evidence that, while effective at improving memory function in models of impaired memory, aniracetam has no effect in improving memory in healthy organisms.


Assuntos
Encéfalo/efeitos dos fármacos , Columbidae/fisiologia , Memória de Curto Prazo/efeitos dos fármacos , Pirrolidinonas/farmacologia , Administração Oral , Animais , Encéfalo/fisiologia , Cognição/efeitos dos fármacos , Cognição/fisiologia , Injeções Intramusculares , Memória de Curto Prazo/fisiologia , Nootrópicos/administração & dosagem , Nootrópicos/farmacocinética , Nootrópicos/farmacologia , Desempenho Psicomotor/efeitos dos fármacos , Pirrolidinonas/administração & dosagem , Pirrolidinonas/farmacocinética , Fatores de Tempo
14.
Eur J Pharm Biopharm ; 139: 262-271, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30981946

RESUMO

The transdermal route offers an attractive alternative route of drug administration especially for Alzheimer's disease patients through eliminating gastrointestinal side effects and ultimately improving compliance. In this study, we prepared an optimized matrix-type patches for the transdermal delivery of galantamine free base with ex vivo and in vitro evaluation. Four pressure sensitive adhesives with different functional groups, ten penetration enhancers and four drug loadings were tested to determine the optimized patch. The ex vivo permeation of the different formulated patches through human cadaver skin using vertical Franz diffusion cells showed that GELVA GMS 788 was the best pressure sensitive adhesive among the tested polymers. FT-IR and rheological studies done to investigate any potential interactions of the polymer with the drug and/or additives showed the possibility of hydrogen bonding between the drug and pressure sensitive adhesive (PSA), also the additives had a plasticization effect causing increased flexibility of the polymer chains. The optimized formulation had 10%w/w drug loading, 5% w/w limonene as a penetration enhancer, and 5%w/w oleic acid as a crystallization inhibitor. The combination of limonene and oleic acid increased the flux of galantamine by 2.7-fold compared to 1.7-fold when limonene was used alone. The optimized patch exhibited diffusion release kinetics and fitted well to Higuchi's model and yielded a permeation rate of 32.4 ±â€¯1.41 µg/cm2/h across human cadaver skin.


Assuntos
Portadores de Fármacos/farmacologia , Galantamina/administração & dosagem , Nootrópicos/administração & dosagem , Absorção Cutânea/efeitos dos fármacos , Adesivo Transdérmico , Adesivos/química , Administração Cutânea , Idoso , Doença de Alzheimer/tratamento farmacológico , Cadáver , Cristalização , Difusão , Portadores de Fármacos/química , Avaliação Pré-Clínica de Medicamentos , Liberação Controlada de Fármacos , Feminino , Galantamina/farmacocinética , Humanos , Limoneno/química , Limoneno/farmacologia , Masculino , Adesão à Medicação , Nootrópicos/farmacocinética , Ácido Oleico/química , Ácido Oleico/farmacologia , Permeabilidade/efeitos dos fármacos , Polímeros/química , Pressão , Pele/efeitos dos fármacos , Pele/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier
15.
Medicine (Baltimore) ; 98(6): e13685, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30732122

RESUMO

BACKGROUND: Previous clinical trials have reported that vinpocetine can be used for the treatment of cognitive dysfunction. However, its efficacy is still inconclusive. In this systematic review study, we aim to assess its efficacy and safety for the treatment of poststroke cognitive dysfunction (PSCD). METHODS: We will search the following electronic databases from the inception to the present to evaluate the efficacy and safety of vinpocetine for patients with PSCD. These databases include CENTRAL, EMBASE, MEDILINE, CINAHL, AMED, and four Chinese databases. All randomized controlled trials (RCTs) of vinpocetine for PSCD will be considered for inclusion without the language restrictions. The methodological quality of all included RCTs will be evaluated by the Cochrane risk of bias tool. The 95% confidence intervals will be utilized to calculate the continuous data, the mean difference or standard mean difference, and dichotomous data with risk ratio. DISSEMINATION AND ETHICS: The results of this review will be disseminated through peer-reviewed journals. Its results may provide important evidence for the clinical practice, as well as the future studies. It does not require ethical approval, because this systematic review will not involve the individual data. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018115224.


Assuntos
Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Nootrópicos/uso terapêutico , Acidente Vascular Cerebral/complicações , Alcaloides de Vinca/uso terapêutico , Humanos , Nootrópicos/administração & dosagem , Nootrópicos/efeitos adversos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Alcaloides de Vinca/administração & dosagem , Alcaloides de Vinca/efeitos adversos
16.
Exp Neurol ; 315: 32-41, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30711647

RESUMO

Approximately 10 million new cases of traumatic brain injury (TBI) are reported each year worldwide with many of these injuries resulting in higher order cognitive impairments. Galantamine (GAL), an acetylcholine esterase inhibitor (AChEI) and positive allosteric modulator of nicotinic acetylcholine receptors (nAChRs), has been reported to ameliorate cognitive deficits after clinical TBI. Previously, we demonstrated that controlled cortical impact (CCI) injury to rats resulted in significant executive function impairments as measured by the attentional set-shifting test (AST), a complex cognitive task analogous to the Wisconsin Card Sorting Test (WCST). We hypothesized that chronic administration of GAL would normalize performance on the AST post-TBI. Isoflurane-anesthetized adult male rats were subjected to moderate CCI (2.8 mm tissue deformation at 4 m/s) or sham injury. Rats were then randomized into one of three treatment groups (i.e., 1 mg/kg GAL, 2 mg/kg GAL, or 1 mL/kg saline vehicle; VEH) or their respective sham controls. GAL or VEH was administered intraperitoneally daily commencing 24 hours post-surgery and until AST testing at 4 weeks post-injury. The AST data revealed significant impairments in the first reversal stage after TBI, seen as increased trials to reach criterion and elevated total errors (p < 0.05). These behavioral flexibility deficits were equally normalized by the administration of both doses of GAL (p < 0.05). Additionally, the higher dose of GAL (2 mg/kg) also significantly reduced cortical lesion volume compared to TBI + VEH controls (p < 0.05). In summary, daily GAL administration provides an efficacious treatment for cognitive deficits and histological recovery after experimental brain trauma. Clinically, these findings are promising considering robust results were attained using a pharmacotherapy already used in the clinic to treat mild dementia.


Assuntos
Atenção/efeitos dos fármacos , Lesões Encefálicas Traumáticas/tratamento farmacológico , Lesões Encefálicas Traumáticas/psicologia , Galantamina/uso terapêutico , Nootrópicos/uso terapêutico , Reversão de Aprendizagem/efeitos dos fármacos , Animais , Lesões Encefálicas Traumáticas/patologia , Córtex Cerebral/patologia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/psicologia , Relação Dose-Resposta a Droga , Função Executiva/efeitos dos fármacos , Galantamina/administração & dosagem , Injeções Intraperitoneais , Masculino , Nootrópicos/administração & dosagem , Desempenho Psicomotor/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
17.
Medicine (Baltimore) ; 98(4): e13931, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30681554

RESUMO

More than 40% dementia patients received traditional Chinese Medicine treatment. However, the prescription pattern of Chinese herbal formulae (CHF) for treating neurocognitive or behavioral disorders in patients with dementia has not been elucidated. This large-scale survey aimed is to evaluate core patterns of CHF and drug-herb concurrent use in patients with dementia.We analyzed patients with a diagnosis of dementia from one million cohorts of the Longitudinal Health Insurance Database in the National Health Insurance Research Database, between 1997 and 2008. Of 18,141 newly diagnosed dementia patients, 3471 patients received CHF for mental and nervous system diseases. There were 13,254 outpatient visits, with 60,968 formulae prescriptions. We calculate the frequency and proportion of combined use, identify drug-herb concurrent usage, and determine core prescription patterns. Also, we drew network graphs of co-prescription pairs which occurred more than 200 times.Chinese medicine prescription patterns changed as dementia progressed.During the first 3 years after the diagnosis of dementia, Jia-Wei-Xiao-Yao-San, Gan-Mai-Da-Zao-Tang, and Ban-Xia-Bai-Zhu-Tian-Ma-Tang were the core CHF prescribed for mental and nervous system disorders. However, during the later stages of dementia, Suan-Zao-Ren-Tang, Gui-Pi-Tang, Jia-Wei-Xiao-Yao-San, and Wen-Dan-Tang were the core CHF prescribed. Benzodiazepines were the most common sedative drugs combined with traditional Chinese formulae.The results of this study suggest that TCM prescription were different in various stages of dementia, and indicated the frequently combined use of the TCM formulae and Benzodiazepines in dementia care.


Assuntos
Fármacos do Sistema Nervoso Central/uso terapêutico , Demência/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Ansiolíticos/administração & dosagem , Antidepressivos/administração & dosagem , Antipsicóticos/administração & dosagem , Fármacos do Sistema Nervoso Central/administração & dosagem , Medicamentos de Ervas Chinesas/uso terapêutico , Glycyrrhiza uralensis , Humanos , Programas Nacionais de Saúde , Nootrópicos/administração & dosagem , Índice de Gravidade de Doença , Taiwan
18.
Subst Use Misuse ; 54(6): 908-920, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30658557

RESUMO

BACKGROUND: Use of prescription stimulants for cognitive enhancement in healthy individuals has been of growing interest to the academic community. University students can be prone to use these pharmacological cognitive enhancers (PCEs) for their perceived academic benefits. OBJECTIVES: We aimed to understand university students' beliefs about the factors influencing PCE use, the cognitive and health effects of the drugs, and how these conceptions are interrelated. METHODS: Data were collected through focus groups with 45 students at the University of Toronto in 2015/2016. We used thematic analysis to extract key themes and cooccurrence coefficients to evaluate the overlap between these themes. RESULTS: We found that participants perceived users as either struggling students or high-achieving ones. Alleged benefits of PCEs included enhanced focus, attention, memorization, and grades, but did not include increased intelligence or long-term cognitive enhancement. Participants disagreed on whether ADHD diagnosis would affect how PCEs worked and how "needing the drug" was determined. Mentions of nonspecific side effects were common, as was the possibility of misuse (e.g., addiction, abuse). Though not an initial aim of the study, we uncovered patterns pertaining to whom participants used as sources of information about different themes. We propose that social learning theory provides a useful framework to explain how the experiences of peers may shape the conceptions of our participants. Conclusions/Importance: Our findings highlight that conceptions surrounding PCEs are multileveled, and informed by a variety of sources, including peers. This should be considered in the development of interventions geared toward university students.


Assuntos
Cognição , Conhecimentos, Atitudes e Prática em Saúde , Nootrópicos/administração & dosagem , Automedicação/psicologia , Estudantes/psicologia , Adulto , Cognição/efeitos dos fármacos , Feminino , Humanos , Masculino , Grupo Associado , Universidades
19.
Clin Pharmacol Ther ; 105(1): 121-130, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29717478

RESUMO

Memantine and the Acetylcholinesterase inhibitors (AChEIs) are two classes of drugs that are used to treat patients with Alzheimer's disease. We conducted a network meta-analysis of randomized controlled trials to compare the treatment effectiveness of monotherapy or combination therapy A total of 23,707 AD patients in 76 randomized trials were identified. In patients with mild-to-moderate AD, monotherapy with donepezil, galantamine or rivastigmine were superior to placebo in enhancing cognitive functions and activities of daily living (ADL), whereas monotherapy with donepezil or memantine were superior to placebo in improving behavioral symptoms. However, combination therapy with AChEIs and memantine did not show additional benefit than monotherapy. In patients with moderate-to-severe AD, neither monotherapy nor combination therapy were superior to placebo in any domain measurement. Combination therapy with memantine and AChEIs is confirmed to have no additional benefits over monotherapy. This article is protected by copyright. All rights reserved.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Inibidores da Colinesterase/administração & dosagem , Dopaminérgicos/administração & dosagem , Memantina/administração & dosagem , Nootrópicos/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/epidemiologia , Humanos , Meta-Análise em Rede , Resultado do Tratamento
20.
Mini Rev Med Chem ; 19(1): 72-78, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30009706

RESUMO

BACKGROUND: Currently, there is no conclusive cure for Alzheimer's disease (AD) and existing treatments mainly offer symptomatic relief. Dysfunction of the cholinergic system plays an important role in the pathogenesis of AD. Tacrine (1, 2, 3, 4-tetrahydroacridin-9-amine, III) was the first approved agent for the palliative therapy of AD but its use is associated with some complications. Development of novel multi target derivatives of Tacrine with lower complications is strongly warranted. In this study, new aminobenzothiazole (1-5, with many useful biological and pharmacological properties) analogues (IV-VIII) were synthesized by changing of amine moiety of III. Then, the effects of these new compounds on learning and memory impairment in scopolamine-induced model of amnesia were studied and the outcomes were compared with control and Tacrine groups in rat. MATERIAL AND METHODS: The rats received Tacrine or its derivatives (IV-VIII) i.p. for two weeks at a dose of 10 mg/kg. For induction of amnesia, scopolamine at a dose of 1 mg/kg was daily administered i.p. started on day-8 till the end of the study. Behavioral experiments including Y-maze, novel object recognition (discrimination) and passive avoidance paradigms were conducted at week 2. RESULTS: Data analysis showed that some Tacrine derivatives, especially VII with 2-amino, 6-nitrobenzothiazole moiety, could markedly and significantly improve alternation score, discrimination ratio and step through latency compared to control and Tacrine groups. CONCLUSION: These findings indicated that some of these derivatives (especially compounds VI and VII) are capable to mitigate learning and memory deficits in scopolamine-induced model of amnesia in rats and may have potential benefit in management of patients with AD.


Assuntos
Amnésia/tratamento farmacológico , Benzotiazóis/química , Benzotiazóis/uso terapêutico , Nootrópicos/química , Nootrópicos/uso terapêutico , Tacrina/análogos & derivados , Tacrina/uso terapêutico , Doença de Alzheimer/tratamento farmacológico , Aminação , Animais , Benzotiazóis/administração & dosagem , Aprendizagem/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Nootrópicos/administração & dosagem , Ratos , Ratos Wistar , Escopolamina , Tacrina/administração & dosagem
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