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61.
Synthesis of Novel Pyrimidin‐4‐One Bearing Piperazine Ring‐Based Amides as Glycogen Synthase Kinase‐3β Inhibitors with Antidepressant Activity 下载免费PDF全文
Imran Khan Mushtaq A. Tantray Hinna Hamid Mohammad Sarwar Alam Abul Kalam Faraz Shaikh Anamik Shah Firasat Hussain 《Chemical biology & drug design》2016,87(5):764-772
Novel pyrimidin‐4‐one derivatives have been synthesized using EDC coupling and evaluated as glycogen synthase kinase‐3β (GSK‐3β) inhibitors. Among all the synthesized compounds, compound 5 (3‐methyl‐6‐phenyl‐2‐(piperazin‐1‐yl)‐3,4‐dihydropyrimidin‐4‐one) exhibited the most potent inhibitory activity against GSK‐3β with IC50 value of 74 nm . The molecular docking studies were performed to elucidate the binding modes of the compounds with the target, and a crucial interaction involving hydrogen bond formation with Val‐135 to the active site of GSK‐3β was observed. Furthermore, the synthesized compounds were subjected to in vivo evaluation of their antidepressant activity, and compound 5 showing highest inhibition of GSK‐3β was also found to significantly reduce the duration of immobility at 50 mg/kg, when compared with fluoxetine, a known antidepressant drug. The results of our study suggest that compound 5 may serve as a valuable template for the design and development of inhibitors of GSK‐3β with antidepressant activity. 相似文献
62.
Introduction: The lifetime prevalence of major depressive episodes in the United States is nearly 17%. Clinical trials and clinical effectiveness studies have demonstrated that many patients will fail to achieve remission using traditional monotherapy, contributing to significant morbidity and suffering. Because of this, augmentation strategies have been proposed to improve both treatment response and remission.Areas covered: Brexpiprazole is a second generation antipsychotic (SGA) approved by the US FDA in 2015 as an add-on treatment to an antidepressant medication for the treatment of adults with MDD, based on the results of two large-scale, randomized, placebo-controlled trials. It is thought to exert its antidepressant effect by a partial agonism of both the dopamine D2 and serotonin 5HT1A receptors. In addition, it also has potent antagonistic activity at 5HT2A, α1B and α2 C receptors, which may also contribute to monoamine transmission regulation.Expert Opinion: Overall, the tolerability of brexpiprazole is promising with relatively low rates of side effects and discontinuation rates, thus establishing it as a new option for the treatment of depression. 相似文献
63.
Ileana L. Piña Katherine E. Di Palo Hector O. Ventura 《Journal of the American College of Cardiology》2018,71(20):2346-2359
This review discusses common mental health disorders and their associations with cardiovascular disease risks. Commonly found mental health disorders include depression, anxiety, and personality types. The link between depression and cardiovascular disease mortality has been established. Depression is also common in patients with heart failure. In addition to discussing psychological disorders, a review of psychotropic drugs is also included. Drugs are described for therapy for depression and anxiety, as well as associations with cardiovascular drug-drug interactions. Drug-drug interactions are more common and potentially dangerous in elderly patients, in whom the conditions often coexist. The most common drug-drug interactions involve the P450 system of enzymes. 相似文献
64.
舒血宁合并阿米替林治疗抑郁症多中心双盲对照研究 总被引:11,自引:0,他引:11
目的:观察合并应用银杏叶提取物能否提高经典抗抑郁药物阿米替林的抗抑郁疗效,能否减少阿米替林的不良反应。方法:采用多中心随机双盲对照研究方法。一组病人给予阿米替林合并银杏叶提取物(研究组),一组给予阿米替林与安慰剂(对照组),治疗8周。共纳入240例符合CCMD-2-R抑郁症标准的病人。结果:(1)研究组疗后Hamilton抑郁量表平均减分率显著高于对照组;(2)研究组治疗结束时CGI严重度显著低于对照组;(3)研究组As-berg副作用量表治疗后增分显著低于对照组。(4)研究组的疗效指数显著高于对照组。结论:银杏叶提取物与阿米替林合并应用可以显著增强后者的抗抑郁疗效,并且能显著减少后者的不良反应,因而提高了后者的疗效指数。 相似文献
65.
66.
p. karling Å. danielsson r. adolfsson † & k.-f. Norrback † 《Neurogastroenterology and motility》2007,19(11):896-904
There is bidirectional comorbidity between anxiety/depression and irritable bowel syndrome (IBS). To investigate the prevalence of IBS symptoms, and factors associated with gastrointestinal symptoms in patients with recurrent depressive disorder. Patients (n = 95) with recurrent type of major depression according to DSM-IV criteria and sex- and age-matched controls (n = 190) were sent questionnaires investigating symptoms of IBS [Gastrointestinal Symptom Rating Scale (GSRS)-IBS] and symptoms of anxiety and depression [Hospital Anxiety and Depression Scale (HADS)]. Medical records were checked over a 10-year period for chronic somatic symptoms or diseases. Seventy-three patients with unipolar disorder (mean age 63.6 years SD 13.8; range 23-86 years) and 156 controls (mean age 59.2 years SD 11.6, range 21-85 years) responded. Patients with recurrent depression had higher GSRS-IBS scores and showed a strong correlation between symptoms of IBS and anxiety-depression (r(s) = 0.54; P < 0.001). IBS symptoms were also associated with multiple pain symptoms, higher health-seeking behaviour and selective-serotonin-reuptake inhibitor intake. However, patients with recurrent depression (n = 46) in remission (HADS-Depression score <8) did not have more symptoms of IBS than controls (GSRS-IBS median score 6.0 vs 6.5; P = 0.46). There is a strong association between symptoms of IBS and symptoms of anxiety and depression, whereas depressive patients in remission do not have more IBS symptoms than controls. 相似文献
67.
Heather A Mitchell Todd H Ahern L Cameron Liles Martin A Javors David Weinshenker 《Neuropsychopharmacology》2006,60(10):1046-1052
BACKGROUND: Acute administration of different classes of antidepressants can enhance or reduce spontaneous locomotor activity in a novel environment, but the effects of chronic antidepressant treatment on spontaneous locomotor activity in novel and familiar environments are less well characterized. Because norepinephrine is an important regulator of spontaneous locomotor activity, we speculated that norepinephrine transporter blockade contributes to the effects of some antidepressants on spontaneous locomotor activity. METHODS: Antidepressant drugs (reboxetine, desipramine, imipramine, venlafaxine, bupropion) were administered acutely (intraperitoneal) or chronically (via osmotic minipump) to control and norepinephrine transporter knockout mice, and spontaneous locomotor activity in novel or familiar environments was recorded. RESULTS: Acute treatment with most norepinephrine transporter-blocking antidepressants decreased spontaneous locomotor activity in a novel environment, whereas chronic treatment decreased spontaneous locomotor activity in both novel and familiar environments. The exception was bupropion, a dual norepinephrine transporter/dopamine transporter blocker, which tended to increase spontaneous locomotor activity. Coadministration of reboxetine and the dopamine transporter blocker GBR 12909 also increased spontaneous locomotor activity. Norepinephrine transporter knockout mice had low basal spontaneous locomotor activity, which was increased by bupropion, whereas reboxetine had no effect in norepinephrine transporter knockout mice. CONCLUSIONS: Acute or chronic inactivation of the norepinephrine transporter decreases spontaneous locomotor activity in novel and familiar environments unless coupled with dopamine transporter blockade. 相似文献
68.
目的 :研究十八症提取物的镇静、镇痛、抗抑郁及抗炎活性。方法 :以十八症的醋酸乙酯提取物和乙醇提取物按 50 ,100mg·kg-1对小鼠分别灌胃给药 ,测定小鼠穿格行走数、扭体数、强迫游泳累计不动时间及耳廓肿胀率来考察十八症提取物的镇静、镇痛、抗抑郁、抗炎活性。结果 :醋酸乙酯提取物可使小鼠穿格行走数、扭体数、累计不动时间及耳廓肿胀率均明显减小 ,而乙醇提取物仅引起小鼠穿格行走数和累计不动时间显著减小。结论 :十八症的醋酸乙酯提取物有较显著的镇静、镇痛、抗抑郁及抗炎作用 ,而乙醇提取物仅在镇静、抗抑郁作用方面具一定活性。 相似文献
69.
老年人脑卒中后抑郁症的发病机制及预防 总被引:1,自引:0,他引:1
[目的]探讨脑卒中后老年患者抑郁症的发病机制及预防措施。[方法]归纳相关资料,对命题进行分析。[结论]医护人员应采取针对性的用药及护理措施,预防患者卒中后抑郁症的发生。 相似文献
70.
苏郁胶囊对抑郁模型小鼠行为及海马神经元损伤的影响 总被引:5,自引:2,他引:5
目的:探究苏郁胶囊对慢性应激抑郁模型小鼠行为、海马神经元损伤及海马突触体内游离Ca2+浓度的影响。方法:将60只昆明种雄性小鼠分为正常组、模型组、苏郁胶囊高、中、低剂量组(22.8,11.4,5.7 g·kg-1)。采用长期不可预见性中等强度应激造成小鼠抑郁模型。测定各组小鼠体重变化,Open-field法和糖水消耗实验测定各组小鼠的行为变化;Nissl染色法观察海马CA1,CA3区神经元形态及锥体细胞数目;以Fura-2负载及荧光分光光度计检测海马突触体内游离Ca2+浓度。结果:与正常组比较,模型组小鼠体重增长缓慢(P<0.01),水平活动得分和垂直活动得分显著减少(P<0.01),糖水消耗量明显降低(P<0.01);海马CA3区锥体细胞数量明显减少(P<0.01);海马突触体内游离Ca2+浓度明显升高(P<0.01);苏郁胶囊高剂量组于第14,21天时小鼠体重增长数明显高于模型组(P<0.05);苏郁胶囊高剂量能增加抑郁小鼠的水平活动得分(P<0.05);苏郁胶囊高、中剂量组能增加抑郁小鼠的垂直活动得分(P<0.01,P<0.05);苏郁胶囊高、中、低剂量能明显增加抑郁小鼠的糖水消耗量(P<0.01,P<0.05,P<0.05);苏郁胶囊高、中、低剂量组能明显增加海马CA3区锥体细胞数量 (P<0.01,P<0.05,P<0.05);苏郁胶囊高、中、低剂量组能明显降低抑郁小鼠海马突触体内游离Ca2+浓度(P<0.01,P<0.01,P<0.05)。结论:苏郁胶囊能改善小鼠的抑郁样行为;保护抑郁模型小鼠海马神经元损伤,其可能与苏郁胶囊抑制海马神经细胞外Ca2+内流,阻止Ca2+超载相关。 相似文献