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1.
Front Neurosci ; 16: 794375, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35720701

RESUMO

Background: Histopathological studies in Wilson's disease (WD) have revealed increased copper and iron concentrations in the deep gray matter nuclei. However, the commonly used mean bulk susceptibility only reflects the regional metal concentration rather than the total metal content, and regional atrophy may affect the assessment of mean bulk susceptibility. Our study aimed to quantitatively assess the changes of metal concentration and total metal content in deep gray matter nuclei by quantitative susceptibility mapping to distinguish patients with neurological and hepatic WD from healthy controls. Methods: Quantitative susceptibility maps were obtained from 20 patients with neurological WD, 10 patients with hepatic WD, and 25 healthy controls on a 3T magnetic resonance imaging system. Mean bulk susceptibility, volumes, and total susceptibility of deep gray matter nuclei in different groups were compared using a linear regression model. The area under the curve (AUC) was calculated by receiver characteristic curve to analyze the diagnostic capability of mean bulk susceptibility and total susceptibility. Results: Mean bulk susceptibility and total susceptibility of multiple deep gray matter nuclei in patients with WD were higher than those in healthy controls. Compared with patients with hepatic WD, patients with neurological WD had higher mean bulk susceptibility but similar total susceptibility in the head of the caudate nuclei, globus pallidus, and putamen. Mean bulk susceptibility of putamen demonstrated the best diagnostic capability for patients with neurological WD, the AUC was 1, and the sensitivity and specificity were all equal to 1. Total susceptibility of pontine tegmentum was most significant for the diagnosis of patients with hepatic WD, the AUC was 0.848, and the sensitivity and specificity were 0.7 and 0.96, respectively. Conclusion: Brain atrophy may affect the assessment of mean bulk susceptibility in the deep gray matter nuclei of patients with WD, and total susceptibility should be an additional metric for total metal content assessment. Mean bulk susceptibility and total susceptibility of deep gray matter nuclei may be helpful for the early diagnosis of WD.

2.
Int J Pharm ; 619: 121651, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35288222

RESUMO

Liposomes functionalized with targeted material offer a breakthrough compared with passive drug delivery. Here, we designed a polymer material, VAP-PEG3350-DSPE (VAP-PEG-DSPE), modified with a d-peptide VAP ligand that combines tumor-homing VAP with GRP78 receptor, a cancer marker on the membranes of many cancer cells. This paper establishes a docetaxel-loaded lipid nanodisk modified with multifunctional material to evaluate its anti-NSCLC efficacy in vivo. Additionally, the present study verified that VAP-conjugated nanodisks adapt to the developed tumor vasculature of the lung cancer microenvironment, making it a promising nanocarrier for NSCLC-targeting therapy. Moreover, in vitro and in vivo experiments demonstrated the targeting ability of VAP-DISK/DTX to tumor cells. Lung slices of mice also demonstrated the safety of VAP-DISK/DTX. The encapsulation efficiency of docetaxel-disks (VAP-DISK/DTX) was as high as 92.46±4.48%. Encapsulating anti-cancer drugs in lipid nanoparticles is thus an effective mechanism to change the pharmacokinetic and pharmacodynamic characteristics of drugs.


Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Nanopartículas , Animais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Linhagem Celular Tumoral , Docetaxel/farmacologia , Sistemas de Liberação de Medicamentos , Lipossomos , Neoplasias Pulmonares/tratamento farmacológico , Camundongos , Camundongos Nus , Peptídeos , Polímeros , Microambiente Tumoral
3.
Psych J ; 11(2): 205-213, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34414691

RESUMO

Recent studies suggest that altered gamma-aminobutyric acidergic (GABAergic) function may result in multisensory integration deficits in schizophrenia. However, it is unclear whether the GABA level is abnormal in individuals with high levels of schizotypal traits and how it would correlate with sensory integration ability in these individuals. This study aimed to compare the GABA level between individuals with high and low levels of negative schizotypy, and examine the relationship between GABA levels and sensory integration ability in each group. In vivo GABA+ and N-acetylaspartate (NAA) levels in the striatum were measured using proton magnetic resonance imaging in 19 participants with high levels of negative schizotypy and 21 participants with low levels of negative schizotypy. The Sensory Integration subscale of the abridged version of the Cambridge Neurological Inventory was used. We examined the group differences in GABA+/NAA levels, and the correlation between striatal GABA+/NAA levels and sensory integration ability in each group. The two groups showed comparable levels of in-vivo GABA+/NAA. In-vivo GABA+/NAA levels were negatively correlated with sensory integration score in participants with low levels of negative schizotypy, but not in participants with high levels of negative schizotypy. Our findings indicate that the increased GABA level is correlated with better sensory integration ability in individuals with low levels of negative schizotypy, implicating the role of GABAergic function in multisensory integration. Unlike schizophrenia patients, individuals with high levels of schizotypy do not exhibit any abnormality in their GABAergic system and sensory integration ability.


Assuntos
Esquizofrenia , Transtorno da Personalidade Esquizotípica , Corpo Estriado , Humanos , Ácido gama-Aminobutírico
4.
Psych J ; 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34794205

RESUMO

This study showed a negative correlation between the glutamate level in the anterior cingulate cortex and cognitive theory of mind in individuals with high level of schizotypy but not in non-schizotypy individuals.

5.
Bioorg Med Chem Lett ; 31: 127681, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33189775

RESUMO

In this study, a series of trans-4-(2-(1,2,4,5-tetrahydro-3H-benzo[d]azepin-3-yl)ethyl)cyclohexan-1-amine derivatives as potential antipsychotics were synthesized and biologically evaluated to discover potential antipsychotics with good drug target selectivity. The preliminary structure-activity relationship was discussed, and optimal compound 12a showed both nanomolar affinity for D2/D3/5-HT1A/5-HT2A receptors and weak α1 and H1 receptor binding affinity. In addition, 12a was metabolically stable in vitro, displayed micromolar affinity for the hERG channel, and exhibited antipsychotic efficacy in the animal model of locomotor-stimulating effects of phencyclidine.


Assuntos
Aminas/farmacologia , Antipsicóticos/farmacologia , Azepinas/farmacologia , Cicloexanos/farmacologia , Receptores Dopaminérgicos/metabolismo , Receptores de Serotonina/metabolismo , Aminas/síntese química , Aminas/química , Animais , Antipsicóticos/síntese química , Antipsicóticos/química , Azepinas/síntese química , Azepinas/química , Cicloexanos/síntese química , Cicloexanos/química , Relação Dose-Resposta a Droga , Humanos , Locomoção/efeitos dos fármacos , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-Atividade
6.
Front Neurosci ; 14: 573633, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33041766

RESUMO

BACKGROUND: Neuropathological studies have revealed copper and iron accumulation in the deep gray matter (DGM) nuclei of patients with Wilson's disease (WD). However, the association between metal accumulation and neurodegeneration in WD has not been well studied in vivo. The study was aimed to investigate whether metal accumulation in the DGM was associated with the structural and functional changes of DGM in neurological WD patients. METHODS: Seventeen neurological WD patients and 20 healthy controls were recruited for the study. Mean bulk susceptibility values and volumes of DGM were obtained from quantitative susceptibility mapping (QSM). Regions of interest including the head of the caudate nucleus, globus pallidus, putamen, thalamus, substantia nigra, red nucleus, and dentate nucleus were manually segmented. The susceptibility values and volumes of DGM in different groups were compared using a linear regression model. Correlations between susceptibility values and volumes of DGM and Unified Wilson's Disease Rating Scale (UWDRS) neurological subscores were investigated. RESULTS: The susceptibility values of all examined DGM in WD patients were higher than those in healthy controls (P < 0.05). Volume reductions were observed in the head of the caudate nucleus, globus pallidus, putamen, thalamus, and substantia nigra of WD patients (P < 0.001). Susceptibility values were negatively correlated with the volumes of the head of the caudate nucleus (r p = -0.657, P = 0.037), putamen (r p = -0.667, P = 0.037), and thalamus (r p = -0.613, P = 0.046) in WD patients. UWDRS neurological subscores were positively correlated with the susceptibility values of all examined DGM. The susceptibility values of putamen, head of the caudate nucleus, and dentate nucleus could well predict UWDRS neurological subscores. CONCLUSION: Our study provided in vivo evidence that paramagnetic metal accumulation in the DGM was associated with DGM atrophy and neurological impairment. The susceptibility of DGM could be used as a biomarker to assess the severity of neurodegeneration in WD.

7.
Bioorg Med Chem Lett ; 29(24): 126769, 2019 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-31699607

RESUMO

A series of novel alkoxy-piperidine derivatives were synthesized and evaluated for their serotonin reuptake inhibitory and binding affinities for 5-HT1A/5-HT7 receptors. In vivo antidepressant activities of the selective compounds were explored using the forced swimming test (FST) and tail suspension test (TST) in mice. The results showed that compounds 7a (reuptake inhibition (RUI), IC50 = 177 nM; 5-HT1A, Ki = 12 nM; 5-HT7, Ki = 25 nM) and 15g (RUI, IC50 = 85 nM; 5-HT1A, Ki = 17 nM; 5-HT7, Ki = 35 nM) were potential antidepressant agents in animal behavioral models with high 5-HT1A/5-HT7 receptor affinities and moderate serotonin reuptake inhibition, and good metabolic stability in vitro.


Assuntos
Antidepressivos/uso terapêutico , Piperidinas/síntese química , Piperidinas/uso terapêutico , Inibidores de Captação de Serotonina/uso terapêutico , Antidepressivos/farmacologia , Humanos , Piperidinas/farmacologia , Inibidores de Captação de Serotonina/farmacologia
8.
Bioorg Med Chem Lett ; 29(23): 126703, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31627993

RESUMO

A series of novel aralkyl piperazine and piperidine derivatives were synthesized, and evaluated for their serotonin reuptake inhibitory and 5-HT1A/5-HT7 receptors affinities activity. Antidepressant activities in vivo of the selective compound were screened using the forced swimming test (FST) and tail suspension test (TST). The results indicated that compound 19a exhibited high affinities for the 5-HT1A/5-HT7 receptors (5-HT1A, Ki = 12 nM; 5-HT7, Ki = 3.2 nM) coupled with potent serotonin reuptake inhibition (IC50 = 14 nM) and showed a marked antidepressant-like effect in the FST and TST models.


Assuntos
Antidepressivos/uso terapêutico , Piperazina/uso terapêutico , Piperidinas/uso terapêutico , Inibidores de Captação de Serotonina/uso terapêutico , Antidepressivos/farmacologia , Humanos , Piperazina/farmacologia , Piperidinas/farmacologia , Inibidores de Captação de Serotonina/farmacologia , Relação Estrutura-Atividade
9.
ACS Nano ; 13(10): 11623-11631, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31532630

RESUMO

Structural dynamics and changes in electronic structures driven by photoexcited carriers are critical issues in both semiconducting and optoelectronic nanodevices. Herein, a phase diagram for the transient states and relevant dynamic processes in multiwalled boron nitride nanotubes (BNNTs) has been extensively studied for a full reversible cycle after a fs-laser excitation in ultrafast TEMs, and the significant structural features and evolution of electronic natures have been investigated using pulsed electron diffraction and femtosecond-resolved electron energy-loss spectroscopy (EELS). It is revealed that nonthermal anisotropic alterations of the lattice apparently precede the phonon-driven thermal transients along the radial and axial directions. Ab initio calculations support these findings and show that electrons excited from the π to π* orbitals in the BN nanotubes weaken the intralayer bonds while strengthening the interlayer bonds along the radial direction. Importantly, time-resolved EELS measurements show contraction of the energy bandgap after fs-laser excitation associated with nonthermal structural transients. This fact verifies that laser-induced bandgap renormalization in semiconductors can essentially be correlated with both the rapid processes of excited carriers and nonthermal lattice evolution.

10.
J Am Chem Soc ; 141(8): 3404-3408, 2019 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-30739447

RESUMO

A quaternary compound Bi3O2S2Cl, which consists of novel [BiS2Cl]2- layers, is reported. It adopts a layered structure of the space group I4/ mmm (No. 139) with lattice parameters: a = 3.927(1) Å, c = 21.720(5) Å. In this compound, bismuth and chlorine atoms form an infinite planar layer, which is unique among the bismuth halides. Superconductivity is observed in both polycrystals and single crystals, and is significantly enhanced in the samples prepared with less sulfur or at higher temperatures. By tuning the content of sulfur, Bi3O2S2Cl can be converted from a semiconductor into a superconductor. The superconducting critical temperature ranges from 2.6 to 3.5 K. Our discovery of the [BiS2Cl]2- layer opens another door in searching for the bismuth compounds with novel physical properties.

11.
Eur J Med Chem ; 144: 701-715, 2018 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-29291438

RESUMO

A series of novel aralkyl piperazine derivatives were synthesized, and evaluated for their serotonin reuptake inhibitory and 5-HT1A/5-HT7 receptors affinities activity. Antidepressant activities in vivo of the compounds were screened using the forced swimming test (FST) and tail suspension test (TST). The results indicated that compounds 21k (RUI, IC50 = 31 nM; 5-HT1A, 5-HT7, ki = 62, 12 nM) and 21n (RUI, IC50 = 25 nM; 5-HT1A, 5-HT7, ki = 28, 3.3 nM) exhibited high affinities for the 5-HT1A/5-HT7 receptors coupled with potent serotonin reuptake inhibition. Specifically, the most promising compound 21n possessed a good oral pharmacokinetic properties and an acceptable hERG profile, and showed potent antidepressant-like effect in the FST and TST models.


Assuntos
Antidepressivos/farmacologia , Piperazinas/farmacologia , Receptor 5-HT1A de Serotonina/metabolismo , Receptores de Serotonina/metabolismo , Inibidores de Captação de Serotonina/farmacologia , Animais , Antidepressivos/síntese química , Antidepressivos/química , Relação Dose-Resposta a Droga , Humanos , Masculino , Estrutura Molecular , Piperazina , Piperazinas/síntese química , Piperazinas/química , Ratos , Ratos Sprague-Dawley , Inibidores de Captação de Serotonina/síntese química , Inibidores de Captação de Serotonina/química , Relação Estrutura-Atividade
12.
Bioorg Med Chem Lett ; 27(24): 5420-5423, 2017 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-29138029

RESUMO

A series of arylalkanol and aralkyl piperazine derivatives have been synthesized and evaluated for 5-HT reuptake inhibitory abilities and binding affinities at the 5-HT1A/5-HT7 receptors. Antidepressant activities of the compounds in vivo were screened using the forced swimming test (FST). The results indicated that the compound 8j exhibited high affinities for the 5-HT1A/5-HT7 receptors (5-HT1A, ki = 0.84 nM; 5-HT7, ki = 12 nM) coupling with moderate 5-HT reuptake inhibitory activity (RUI, IC50 = 100 nM) and showed a marked antidepressant-like activity in the FST model.


Assuntos
Antidepressivos/síntese química , Piperazinas/química , Receptor 5-HT1A de Serotonina/metabolismo , Receptores de Serotonina/metabolismo , Inibidores de Captação de Serotonina/síntese química , Animais , Antidepressivos/metabolismo , Antidepressivos/farmacologia , Células HEK293 , Meia-Vida , Humanos , Concentração Inibidora 50 , Camundongos , Microssomos Hepáticos/metabolismo , Atividade Motora/efeitos dos fármacos , Piperazinas/metabolismo , Piperazinas/farmacologia , Ratos , Receptor 5-HT1A de Serotonina/química , Receptores de Serotonina/química , Inibidores de Captação de Serotonina/metabolismo , Inibidores de Captação de Serotonina/farmacologia , Relação Estrutura-Atividade
13.
Eur J Med Chem ; 123: 332-353, 2016 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-27487565

RESUMO

A series of novel benzisothiazolylpiperazine derivatives combining potent dopamine D2 and D3, and serotonin 5-HT1A and 5-HT2A receptor properties were synthesized and evaluated for their potential antipsychotic properties. The most-promising derivative was 9j. The unique pharmacological features of 9j were a high affinity for D2, D3, 5-HT1A, and 5-HT2A receptors, together with a 20-fold selectivity for the D3 versus D2 subtype, and a low affinity for muscarinic M1 (reducing the risk of anticholinergic side effects), and for hERG channels (reducing incidence of QT interval prolongation). In animal behavioral models, 9j inhibited the locomotor-stimulating effects of phencyclidine, blocked conditioned avoidance response, and improved the cognitive deficit in the novel object recognition tests in rats. 9j exhibited a low potential for catalepsy, consistent with results with risperidone. In addition, favorable brain penetration of 9j in rats was detected. These studies have demonstrated that 9j is a potential atypical antipsychotic candidate.


Assuntos
Amidas/síntese química , Amidas/farmacologia , Antipsicóticos/síntese química , Antipsicóticos/farmacologia , Piperazinas/química , Receptores de Superfície Celular/metabolismo , Amidas/efeitos adversos , Amidas/farmacocinética , Animais , Antipsicóticos/efeitos adversos , Antipsicóticos/farmacocinética , Comportamento Animal/efeitos dos fármacos , Catalepsia/induzido quimicamente , Catalepsia/fisiopatologia , Cognição/efeitos dos fármacos , Locomoção/efeitos dos fármacos , Masculino , Piperazina , Ratos , Ratos Sprague-Dawley , Relação Estrutura-Atividade
14.
Nanoscale ; 8(11): 6094-100, 2016 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-26932298

RESUMO

On-demand drug delivery is becoming feasible via the design of either exogenous or endogenous stimulus-responsive drug delivery systems. Herein we report the development of gadolinium arsenite nanoparticles as a self-delivery platform to store, deliver and release arsenic trioxide (ATO, Trisenox), a clinical anti-cancer drug. Specifically, unloading of the small molecule drug is triggered by an endogenous stimulus: inorganic phosphate (Pi) in the blood, fluid, and soft or hard tissue. Kinetics in vitro demonstrated that ATO is released with high ON/OFF specificity and no leakage was observed in the silent state. The nanoparticles induced tumor cell apoptosis, and reduced cancer cell migration and invasion. Plasma pharmacokinetics verified extended retention time, but no obvious disturbance of phosphate balance. Therapeutic efficacy on a liver cancer xenograft mouse model was dramatically potentiated with reduced toxicity compared to the free drug. These results suggest a new drug delivery strategy which might be applied for ATO therapy on solid tumors.


Assuntos
Antineoplásicos/química , Arsenicais/química , Sistemas de Liberação de Medicamentos , Óxidos/química , Fosfatos/química , Animais , Apoptose , Trióxido de Arsênio , Linhagem Celular Tumoral , Movimento Celular , Dextranos/química , Feminino , Células Hep G2 , Humanos , Cinética , Neoplasias Hepáticas/patologia , Camundongos , Microscopia Eletrônica de Transmissão , Nanopartículas , Invasividade Neoplásica , Transplante de Neoplasias , Ratos , Espectroscopia de Infravermelho com Transformada de Fourier , Termodinâmica
15.
Eur J Med Chem ; 86: 219-34, 2014 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-25164761

RESUMO

A series of aralkyl diamine derivatives were designed, synthesized, and evaluated for their triple reuptake inhibitory abilities. Compounds 18c (5-HT, NE, DA, IC50 = 389, 69, 238 nM), 36a (5-HT, NE, DA, IC50 = 378, 477, 247 nM), and 36d (5-HT, NE, DA, IC50 = 501, 206, 357 nM) showed in vivo activities in the rat forced swim test at 5, 10, and 20 mg/kg PO. 36a was identified as the most promising candidate in this study. Specifically, 36a exhibited high selectivity for monoamine transporters over a number of CNS-related targets. Furthermore, 36a showed a good pharmacokinetic properties and acceptable safety profile in preclinical studies.


Assuntos
Diaminas/farmacologia , Dopamina/metabolismo , Norepinefrina/antagonistas & inibidores , Serotonina/metabolismo , Animais , Diaminas/síntese química , Diaminas/química , Relação Dose-Resposta a Droga , Feminino , Células HEK293 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos , Estrutura Molecular , Norepinefrina/metabolismo , Ratos , Relação Estrutura-Atividade
16.
Oncol Lett ; 8(2): 891-897, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25009663

RESUMO

Metastasis-associated in colon cancer 1 (MACC1) is a newly identified gene that has been shown to promote tumor cell invasion and metastasis. The present study investigated the effect of MACC1 downregulation on the biological characteristics of the ovarian cancer OVCAR3 cell line. In this study, MACC1 expression was blocked using the RNA interference technique. The downregulation of MACC1 mRNA and protein expression was confirmed using quantitative polymerase chain reaction and western blot analysis. The proliferative activity and adhesion rate of the cells were detected using cell counting kit-8 and a cell adhesion assay, while cell invasion was determined using a Matrigel invasion assay and migration capacity was observed using migration and wound-healing assays. A tube formation assay was also used to examine the angiogenic capacity of cells, and a luciferase assay was performed to assess whether MACC1 binds to the c-MET gene. The MACC1 mRNA and protein expression levels were significantly downregulated using sequence-specific small interfering RNA (siRNA). The inhibition of MACC1 expression markedly decreased the invasive, metastatic and angiogenic capacities of the cells, but only slightly inhibited growth and adhesion. In addition, a putative MACC1-binding site was identified in the 3'-untranslated region of c-MET. MACC1-siRNA was also found to significantly reduce the expression of the c-MET protein and a luciferase reporter assay confirmed that c-MET was the target gene of MACC1. These results demonstrated that the attenuation of MACC1 suppresses cell invasion and migration and that MACC1 may regulate cell metastasis through targeting the expression of c-MET. Inhibition of the function of MACC1 may represent a new strategy for treating ovarian cancer.

17.
Acta Pharmacol Sin ; 34(9): 1149-55, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23892272

RESUMO

AIM: SKF83959 (3-methyl-6-chloro-7,8-hydroxy-1-(3-methylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine) is an atypical dopamine receptor-1 (D1 receptor) agonist, which exhibits many D1 receptor-independent effects. In the present work, we examined the effects of SKF83959 on monoaminergic transporters in vitro and its anti-depressant activity in vivo. METHODS: Human serotonin transporter (SERT), norepinephrine transporters (NET) or dopamine transporters (DAT) were stably expressed in CHO cells. The uptake kinetics of SERT, NET, and DAT were examined using [(3)H]-serotonin, [(3)H]-norepinephrine or [(3)H]-dopamine, respectively. A triple reuptake inhibitor DOV21947 was used as the positive control. Tail suspension test and forced swimming test were conducted in mice. SKF83959 or DOV21947 (2-8 mg/kg) were intraperitoneally injected 30 min before the tests. RESULTS: SKF83959 was a competitive inhibitor of SERT (K(i)=1.43±0.45 µmol/L), but a noncompetitive inhibitor of NET (K(i)=0.60±0.07 µmol/L) and DAT (K(i)=9.01±0.80 µmol/L). In contrast, DOV21947 was a competitive inhibitor of SERT (K(i)=0.89±0.24 µmol/L) and DAT (K(i)=1.47±0.31 µmol/L) and a noncompetitive inhibitor of NET (K(i)=0.18±0.04 µmol/L). In mice, both SKF83959 and DOV21947 elicited anti-depressant activity in a dose-dependent manner. CONCLUSION: SKF83959 functions as a novel triple reuptake inhibitor in vitro and exerts anti-depressant effects in vivo.


Assuntos
2,3,4,5-Tetra-Hidro-7,8-Di-Hidroxi-1-Fenil-1H-3-Benzazepina/análogos & derivados , Antidepressivos/farmacologia , Proteínas da Membrana Plasmática de Transporte de Dopamina/antagonistas & inibidores , Proteínas da Membrana Plasmática de Transporte de Norepinefrina/antagonistas & inibidores , Proteínas da Membrana Plasmática de Transporte de Serotonina , 2,3,4,5-Tetra-Hidro-7,8-Di-Hidroxi-1-Fenil-1H-3-Benzazepina/farmacologia , 2,3,4,5-Tetra-Hidro-7,8-Di-Hidroxi-1-Fenil-1H-3-Benzazepina/uso terapêutico , Animais , Antidepressivos/uso terapêutico , Células CHO , Cricetinae , Cricetulus , Depressão/tratamento farmacológico , Depressão/metabolismo , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Relação Dose-Resposta a Droga , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas da Membrana Plasmática de Transporte de Norepinefrina/metabolismo , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo
18.
Sci Rep ; 3: 1245, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23409236

RESUMO

Magnetoelectric multiferroics are materials that have coupled magnetic and electric dipole orders, which can bring novel physical phenomena and offer possibilities for new device functions. In this report, single-crystalline Bi(4.2)K(0.8)Fe(2)O(9+δ) nanobelts which are isostructural with the high-temperature superconductor Bi(2)Sr(2)CaCu(2)O(8+δ) are successfully grown by a hydrothermal method. The regular stacking of the rock salt slabs and the BiFeO(3)-like perovskite blocks along the c axis of the crystal makes the Bi(4.2)K(0.8)Fe(2)O(9+δ) nanobelts have a natural magnetoelectric-dielectric superlattice structure. The most striking result is that the bulk material made of the Bi(4.2)K(0.8)Fe(2)O(9+δ) nanobelts is of multiferroicity near room temperature accompanied with a structure anomaly. When an external magnetic field is applied, the electric polarization is greatly suppressed, and correspondingly, a large negative magnetocapacitance coefficient is observed around 270 K possibly due to the magnetoelectric coupling effect. Our result provides contributions to the development of single phase multiferroics.

19.
Yao Xue Xue Bao ; 47(6): 755-63, 2012 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-22919723

RESUMO

Compounds with serotonin reuptake inhibition/5-HT(1A) dual activity were used to build 3D pharmacophore model as a training molecules by Discover Studio. Based on the model, 8 novel aryl piperazine benzo[b][1,4] oxazine derivatives were designed and synthesized, and their structures were confirmed by 1H NMR and HR-MS. Biological evaluation illustrated that compounds VI(1) and VI(7) showed potent functional activities at both 5-HT transporter and 5-HT(1A) receptor, which can be used as lead compounds to guide future research of design and synthesis of potent novel compounds.


Assuntos
Desenho de Fármacos , Oxazinas/síntese química , Piperazinas/síntese química , Animais , Células CHO , Cricetinae , Cricetulus , Vetores Genéticos , Estrutura Molecular , Oxazinas/química , Oxazinas/farmacologia , Piperazina , Piperazinas/química , Piperazinas/farmacologia , Plasmídeos , Ligação Proteica , Receptor 5-HT1A de Serotonina/genética , Receptor 5-HT1A de Serotonina/metabolismo , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Inibidores de Captação de Serotonina/metabolismo , Relação Estrutura-Atividade , Transfecção
20.
Eur J Med Chem ; 54: 123-36, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22608762

RESUMO

A series of arylalkanol-piperidine derivatives was synthesized, and their triple reuptake inhibition and in vivo activities have been evaluated. Among them, compounds 2a, 2j, 2k, 2m and 2n exhibited high potency for 5-HT, NA and DA transporters. Optimized compounds 2j and 2m showed significant reduction of immobility time compared to that of vehicle in the mouse tail suspension test (TST) test at doses ranging from 10 to 50 mg/kg po, and were not generally motor stimulants at 50 mg/kg dose. In addition, compounds 2j and 2m displayed desirable pharmacokinetic properties in SD rats.


Assuntos
Antidepressivos/química , Antidepressivos/farmacologia , Inibidores da Captação de Neurotransmissores/química , Inibidores da Captação de Neurotransmissores/farmacologia , Piperidinas/química , Piperidinas/farmacologia , Animais , Antidepressivos/metabolismo , Antidepressivos/farmacocinética , Técnicas de Química Sintética , Masculino , Camundongos , Inibidores da Captação de Neurotransmissores/metabolismo , Inibidores da Captação de Neurotransmissores/farmacocinética , Piperidinas/metabolismo , Piperidinas/farmacocinética , Ratos , Ratos Sprague-Dawley , Receptores de Amina Biogênica/metabolismo
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