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931.
Cristiano R. Jesse 《Pharmacology, biochemistry, and behavior》2010,95(3):344-350
The involvement of the noradrenergic system, imidazoline, dopaminergic and adenosinergic receptors in the antidepressant-like action of tramadol in the mouse forced swimming test (FST) was evaluated in this study. The antidepressant-like effect of tramadol (40 mg/kg, per oral, p.o.) in the FST was blocked with yohimbine (1 mg/kg, i.p., an α2-adrenoceptor antagonist), α-methyl-para-tyrosine methyl ester (AMPT, 100 mg/kg, i.p., an inhibitor of tyrosine hydroxylase), efaroxan (1 mg/kg, i.p., an imidazoline I1/α2-adrenoceptor antagonist), idazoxan (0.06 mg/kg, i.p., an imidazoline I2/α2-adrenoceptor antagonist), antazoline (5 mg/kg, i.p., a ligand with high affinity for the I2 receptor), haloperidol (0.2 mg/kg, i.p., a non selective dopamine receptor antagonist), SCH23390 (0.05 mg/kg, subcutaneously, s.c., a dopamine D1 receptor antagonist), sulpiride (50 mg/kg, i.p., a dopamine D2 and D3 receptor antagonist) but was not reversed by prazosin (1 mg/kg, intraperitoneally, i.p., an α1-adrenoceptor antagonist) and caffeine (3 mg/kg, i.p., a nonselective adenosine receptor antagonist). Monoamine oxidase-A and -B (MAO-A and MAO-B) activities were neither inhibited in the whole brain nor in specific brain regions of mice treated with tramadol. These data demonstrated that the antidepressant-like effect caused by oral administration of tramadol in the mouse FST is mediated by the noradrenergic system, dopaminergic and imidazoline receptors. 相似文献
932.
Depressive symptoms are very frequent over a lifetime, especially for women. Menopause is a period of higher depressive vulnerability. There are suggestive data that estrogen deficiency may increase the susceptibility for depression. We studied whether a bilateral ovariectomy (OVX) modifies mice behaviors and antidepressant drug effects through tail suspension test (TST). We evaluated behavioral changes at 1 week, 2 weeks, and up to 2 months after OVX. The behavior responses to doxepin, paroxetine, and venlafaxine at 1 week, 2 weeks, and 2 months after OVX were evaluated. No obvious difference was detected on the duration of immobility among control group, sham group, and OVX group in the TST at 1 week and 2 weeks after OVX. But the duration of immobility of OVX group was distinctly longer than that of both control group and sham operation group at 2 months after OVX. At 1 and 2 weeks after OVX, only the antidepressant response to venlafaxine was observed, while response to paroxetine increased 2 months after OVX. Response to antidepressant drugs was strongly modified in OVX mice. The present results suggest that not all antidepressant drugs are appropriate for depression with estrogen deficiency. 相似文献
933.
抑郁症是一种高患病、高复发的精神类疾病。目前临床常用的抗抑郁药物,主要是基于上世纪50年代开发的三环类和单胺氧化酶抑制剂,其通过调节脑中5-羟色胺或去甲肾上腺素的水平,缓解患者的抑郁症状。新研发的抗抑郁药虽然特异性较以往有所提升,但仍然存在起效慢、患者应答率低和副作用严重等弊端。虫草素是我国传统中医药材冬虫夏草的主要活性成分。本文通过综述现有文献,讨论虫草素的抗抑郁效果及其涉及的生物学机制,为传统中医药材的研发应用和中医现代化进程提供新的思路和参考。 相似文献
934.
Jeffrey S Burgdorf Xiao-Lei Zhang Patric K Stanton Joseph R Moskal John E Donello 《The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP)》2022,25(12):979
BackgroundThe role of glutamatergic receptors in major depressive disorder continues to be of great interest for therapeutic development. Recent studies suggest that both negative and positive modulation of N-methyl-D-aspartate receptors (NMDAR) can produce rapid antidepressant effects. Here we report that zelquistinel, a novel NMDAR allosteric modulator, exhibits high oral bioavailability and dose-proportional exposures in plasma and the central nervous system and produces rapid and sustained antidepressant-like effects in rodents by enhancing activity-dependent, long-term synaptic plasticity.MethodsNMDAR-mediated functional activity was measured in cultured rat brain cortical neurons (calcium imaging), hNR2A or B subtype-expressing HEK cells, and synaptic plasticity in rat hippocampal and medial prefrontal cortex slices in vitro. Pharmacokinetics were evaluated in rats following oral administration. Antidepressant-like effects were assessed in the rat forced swim test and the chronic social deficit mouse model. Target engagement and the safety/tolerability profile was assessed using phencyclidine-induced hyperlocomotion and rotarod rodent models.ResultsFollowing a single oral dose, zelquistinel (0.1–100 µg/kg) produced rapid and sustained antidepressant-like effects in the rodent depression models. Brain/ cerebrospinal fluid concentrations associated with zelquistinel antidepressant-like activity also increased NMDAR function and rapidly and persistently enhanced activity-dependent synaptic plasticity (long-term potentiation), suggesting that zelquistinel produces antidepressant-like effects by enhancing NMDAR function and synaptic plasticity. Furthermore, Zelquistinel inhibited phencyclidine (an NMDAR antagonist)-induced hyperlocomotion and did not impact rotarod performance.ConclusionsZelquistinel produces rapid and sustained antidepressant effects by positively modulating the NMDARs, thereby enhancing long-term potentiation of synaptic transmission. 相似文献
935.
抗抑郁药文拉法辛的合成研究 总被引:4,自引:0,他引:4
以苯甲醚为起始原料,采用新路线经傅克酰化、胺化、还原、溴代、格氏五步反应制得新型抗抑郁药文拉法辛(venlafaxine) ,总收率为11 % ,反应原料易得,反应条件温和,后处理方便,适合工业化生产。 相似文献
936.
ObjectiveSerotonergic dysfunction may be involved in the etiology of overall neuropsychiatric symptoms (NPS) and agitation in patients with dementia; therefore, we aim to perform a systematic review and meta-analysis to investigate the efficacy of serotonergic antidepressants in such populations.MethodsWe systematically searched PubMed, Medline, Embase, and Cochrane Library to obtain randomized controlled trials (RCTs) from the date of their inception until December 11, 2020 to examine the effect of serotonergic antidepressants on the outcomes of interest in patients with dementia. Data were pooled using a random-effects model. Co-primary outcomes were mean changes in overall NPS and agitation as a specific symptom of NPS. Secondary outcomes were mean changes in depressive symptoms, cognition, and care burden.ResultsFourteen randomized controlled trials were eligible (n = 1,374; mean age = 76.8 years; mean proportion of female = 61.9 %). Serotonergic antidepressants significantly reduced the overall NPS (k = 12, n = 1276, Hedges’ g = −0.49, 95 % confidence intervals [CIs] = -0.74 to -0.24, p < 0.001) and agitation severity (k = 9, n = 749, Hedges’ g = −0.28, 95 % CIs = −0.43 to −0.14, p < 0.001), both with small effect size in patients with dementia. For secondary outcome, serotonergic antidepressants also significantly improved depressive symptoms, cognition, and care burden with small to very small effect sizes (depressive symptoms, k = 8, n = 938, Hedges’ g = −0.32, 95 % CIs = −0.49 to −0.15, p < 0.001;cognition, k = 6, n = 983, Hedges’ g = 0.15, 95 % CIs = 0.002 to 0.29, p = 0.046; care burden, k = 7, n = 961, Hedges’ g = −0.24, 95 % CIs = −0.41 to −0.07, p = 0.005). Subgroup analysis showed that both selective serotonin reuptake inhibitors (SSRIs) and non-SSRIs significant reduced agitation and depressive symptoms (For agitation, SSRIs, k = 6, n = 605, Hedges’ g = −0.25, 95 % CIs = −0.41 to −0.09, p=0.002; non-SSRIs, k = 3, n = 144, Hedges’ g = −0.41, 95 % CIs = −0.74 to −0.08, p = 0.016; For depression, SSRIs, k = 6, n = 736, Hedges’ g = −0.29, 95 % CIs = −0.48 to −0.09, p=0.004; non-SSRIs, k = 343, n = 144, Hedges’ g = −0.43, 95 % CIs = −0.78 to −0.09, p = 0.016), whereas only SSRIs reduced overall NPS (k = 9, n = 1109, Hedges’ g = −0.49, 95 % CIs = −0.78 to −0.20, p = 0.001) and care burden (k = 5, n = 740, Hedges’ g = −0.29, 95 % CIs = −0.50 to −0.08, p=0.007).ConclusionThe present meta-analysis indicates that serotonergic antidepressants effectively alleviate overall NPS, agitation, depressive symptoms, and care burden, and improve cognitive function. 相似文献
937.
目的:比较多种抗抑郁药治疗儿童青少年抑郁症的效果,为儿童青少年抑郁症的治疗提供疗效与耐受性方面的依据。方法:在PubMed、Cochrane Library、EMBASE、Web of Science、PsycINFO、中国生物医学文献数据库、中国知网和万方数据知识服务平台等数据库中检索关于抗抑郁药治疗儿童青少年抑郁症的随机对照试验,检索时间截至2021年12月。对纳入文献进行质量评价及数据提取,采用Stata 15.1软件对有效率、耐受性进行分析,采用累积排序概率曲线下面积(SUCAR)评估药物有效率和耐受性的累积概率。结果:最终纳入32篇文献的33项随机对照试验研究,共6949例患者,涉及阿米替林、维拉唑酮、氟西汀、司来吉兰、帕罗西汀、丙咪嗪、地昔帕明、舍曲林、去甲替林、艾司西酞普兰、西酞普兰、文拉法辛、度洛西汀等13种抗抑郁药。网状meta分析结果显示,度洛西汀(OR=1.95,95%CI:1.41~2.69)、氟西汀(OR=1.73,95%CI:1.40~2.14)、文拉法辛(OR=1.37,95%CI:1.04~1.80)、艾司西酞普兰(OR=1.48,95%CI:1.12~... 相似文献
938.
RATIONALE: Bupropion is an atypical antidepressant and the only non-nicotine-based therapy approved for smoking cessation. Its use has raised much debate as to how a non-nicotine-based agent can aid in smoking cessation. OBJECTIVES: We assessed the effects of bupropion on brain reward function under baseline conditions and subsequent to withdrawal from chronic nicotine administration in rats. METHODS: A discrete-trial intracranial self-stimulation paradigm procedure was used that provides one with current intensity thresholds, a measure of reward in rats under baseline conditions and subsequent to withdrawal from chronic nicotine (3.16 mg/kg per day for 7 days via osmotic minipump). Somatic signs were recorded based on a checklist of nicotine abstinence signs in animals withdrawn from nicotine. RESULTS: Bupropion (10-60 mg/kg) dose-dependently lowered reward thresholds in non-withdrawing subjects indicating an increase in reward. Interestingly, a sub-effective dose of bupropion (5 mg/kg) blocked completely the threshold lowering effects of acute nicotine (0.25 mg/kg). Animals withdrawn from chronic nicotine exhibited increases in somatic signs of withdrawal and elevated brain reward thresholds, which is indicative of "diminished interest or pleasure" (i.e. anhedonia) in the rewarding stimuli. Bupropion (10-40 mg/kg) reversed both the reward deficit and the somatic signs, with the highest dose (40 mg/kg) inducing a protracted reversal of the threshold elevation. CONCLUSIONS: Bupropion acts on multiple levels to alter brain reward circuits influenced by nicotine, in addition to reducing the expression of somatic signs of withdrawal. First, bupropion, unlike other antidepressants, increases brain reward function under baseline conditions in non-withdrawing subjects. Second, at low doses bupropion blocks the rewarding effects of nicotine. Third, bupropion reverses the negative affective aspects of nicotine withdrawal. Such actions are likely to act in concert to mediate the unique anti-smoking properties of bupropion. 相似文献
939.
蒙中医药对抑郁症认识有别,蒙医药认为抑郁症是由赫依偏盛所致,治疗重在调节赫依、平衡三根、宁心安神、促进白脉传导;中医药认为肝郁气滞、情志不遂为抑郁症的核心病机,治疗以疏肝解郁,兼顾心脾为主。槟榔十三味丸为蒙医调节赫依的经典名方,具有调节赫依,安神止痛之功,通过调节赫依,平衡三根,促进了白脉的传导,达到治疗抑郁症的目的。蒙医认为脑为白脉之海,故槟榔十三味丸治疗抑郁症的机制实则为心脑同治。进而从中医药角度分析槟榔十三味丸,发现其多用辛味药,能行气温中,因而调理中焦脾胃气机可能是其治疗抑郁症的重要途径,温补肾阳的功效也提示其通过心脑肾同调治疗抑郁症。因此在抑郁症的临床治疗中,中医可以学习蒙医辛味药的用药经验,重视调理脾胃气机和温补肾阳;中医治疗抑郁症多从肝论治,所以蒙医也可以借鉴中医疏肝解郁药的应用经验。 相似文献
940.