• 【对抗抑郁药物的依从性: 对社区药剂师咨询实践的评估。】 复制标题 收藏 收藏
    DOI:10.2147/PPA.S48486 复制DOI
    作者列表:Chong WW,Aslani P,Chen TF
    BACKGROUND & AIMS: BACKGROUND:Recent studies have shown that pharmacists have a role in addressing antidepressant nonadherence. However, few studies have explored community pharmacists' actual counseling practices in response to antidepressant adherence-related issues at various phases of treatment. The purpose of this study was to evaluate counseling practices of community pharmacists in response to antidepressant adherence-related issues. METHODS:A simulated patient method was used to evaluate pharmacist counseling practices in Sydney, Australia. Twenty community pharmacists received three simulated patient visits concerning antidepressant adherence-related scenarios at different phases of treatment: 1) patient receiving a first-time antidepressant prescription and hesitant to begin treatment; 2) patient perceiving lack of treatment efficacy for antidepressant after starting treatment for 2 weeks; and 3) patient wanting to discontinue antidepressant treatment after 3 months due to perceived symptom improvement. The interactions were recorded and analyzed to evaluate the content of consultations in terms of information gathering, information provision including key educational messages, and treatment recommendations. RESULTS:There was variability among community pharmacists in terms of the extent and content of information gathered and provided. In scenario 1, while some key educational messages such as possible side effects and expected benefits from antidepressants were mentioned frequently, others such as the recommended length of treatment and adherence-related messages were rarely addressed. In all scenarios, about two thirds of pharmacists explored patients' concerns about antidepressant treatment. In scenarios 2 and 3, only half of all pharmacists' consultations involved questions to assess the patient's medication use. The pharmacists' main recommendation in response to the patient query was to refer the patient back to the prescribing physician. CONCLUSION:The majority of pharmacists provided information about the risks and benefits of antidepressant treatment. However, there remains scope for improvement in community pharmacists' counseling practice for patients on antidepressant treatment, particularly in providing key educational messages including adherence-related messages, exploring patients' concerns, and monitoring medication adherence.
    背景与目标:
  • 【氯胺酮在难治性重度抑郁症中的抗抑郁作用: 一项两中心随机对照试验。】 复制标题 收藏 收藏
    DOI:10.1176/appi.ajp.2013.13030392 复制DOI
    作者列表:Murrough JW,Iosifescu DV,Chang LC,Al Jurdi RK,Green CE,Perez AM,Iqbal S,Pillemer S,Foulkes A,Shah A,Charney DS,Mathew SJ
    BACKGROUND & AIMS: OBJECTIVE:Ketamine, a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist, has shown rapid antidepressant effects, but small study groups and inadequate control conditions in prior studies have precluded a definitive conclusion. The authors evaluated the rapid antidepressant efficacy of ketamine in a large group of patients with treatment-resistant major depression. METHOD:This was a two-site, parallel-arm, randomized controlled trial of a single infusion of ketamine compared to an active placebo control condition, the anesthetic midazolam. Patients with treatment-resistant major depression experiencing a major depressive episode were randomly assigned under double-blind conditions to receive a single intravenous infusion of ketamine or midazolam in a 2:1 ratio (N=73). The primary outcome was change in depression severity 24 hours after drug administration, as assessed by the Montgomery-Åsberg Depression Rating Scale (MADRS). RESULTS:The ketamine group had greater improvement in the MADRS score than the midazolam group 24 hours after treatment. After adjustment for baseline scores and site, the MADRS score was lower in the ketamine group than in the midazolam group by 7.95 points (95% confidence interval [CI], 3.20 to 12.71). The likelihood of response at 24 hours was greater with ketamine than with midazolam (odds ratio, 2.18; 95% CI, 1.21 to 4.14), with response rates of 64% and 28%, respectively. CONCLUSIONS:Ketamine demonstrated rapid antidepressant effects in an optimized study design, further supporting NMDA receptor modulation as a novel mechanism for accelerated improvement in severe and chronic forms of depression. More information on response durability and safety is required before implementation in clinical practice.
    背景与目标:
  • 【kisspeptin-13抗抑郁药样作用的神经传递。】 复制标题 收藏 收藏
    DOI:10.1016/j.regpep.2012.08.017 复制DOI
    作者列表:Tanaka M,Csabafi K,Telegdy G
    BACKGROUND & AIMS: :Kisspeptins are G protein-coupled receptor ligands originally identified as human metastasis suppressor gene products that have the ability to suppress melanoma and breast cancer metastasis and which have recently been found to play an important role in initiating the secretion of gonadotropin-releasing hormone at puberty. In the brain, the gene is transcribed within the hippocampal dentate gyrus. Kisspeptin-13, one of the endogenous isoforms, consists of 13 amino acids. In this work, antidepressant-like effects of kisspeptin-13 were studied and the potential involvement of the adrenergic, serotonergic, cholinergic, dopaminergic and gabaergic receptors in its antidepressant-like effects was investigated in a modified forced swimming test (FST) in mice. The mice were pretreated with a nonselective α-adrenergic receptor antagonist, phenoxybenzamine, an α(1)/α(2β)-adrenergic receptor antagonist, prazosin, an α(2)-adrenergic receptor antagonist, yohimbine, a β-adrenergic receptor antagonist, propranolol, a mixed 5-HT(1)/5-HT(2) serotonergic receptor antagonist, methysergide, a nonselective 5-HT(2) serotonergic receptor antagonist, cyproheptadine, a nonselective muscarinic acetylcholine receptor antagonist, atropine, a D(2),D(3),D(4) dopamine receptor antagonist, haloperidol, or a γ-aminobutyric acid subunit A receptor antagonist, bicuculline. The FST revealed that kisspeptin-13 reversed the immobility, climbing and swimming times, suggesting antidepressant-like effects. Phenoxybenzamine, yohimbine and cyproheptadine prevented the effects of kisspeptin-13 on the immobility, climbing and swimming times, whereas prazosin, propranolol, methysergide, atropine, haloperidol and bicuculline did not modify the effects of kisspeptin-13. The results demonstrated that the antidepressant-like effects of kisspeptin-13 in a modified mouse FST are mediated, at least in part, by an interaction of the α(2)-adrenergic and 5-HT(2) serotonergic receptors.
    背景与目标: : kisspeptin是g蛋白偶联受体配体,最初被确定为人类转移抑制基因产物,具有抑制黑色素瘤和乳腺癌转移的能力,最近发现它们在启动促性腺激素释放激素的分泌中起重要作用青春期的激素。在大脑中,该基因在海马齿状回内转录。Kisspeptin-13是内源性同工型之一,由13个氨基酸组成。在这项工作中,研究了kisspeptin-13的抗抑郁药样作用,并在改良的强迫游泳试验 (FST) 中研究了肾上腺素能,血清素能,胆碱能,多巴胺能和gaba能受体在其抗抑郁药样作用中的潜在参与。小鼠。用非选择性 α-肾上腺素能受体拮抗剂苯氧基苯甲胺,α(1)/α(2β)-肾上腺素能受体拮抗剂,哌唑嗪,α(2)-肾上腺素能受体拮抗剂,育亨宾,β-肾上腺素能受体拮抗剂,普萘洛尔,混合5-HT(1)/5-HT(2) 5-羟色胺能受体拮抗剂,methysergide,非选择性5-HT(2) 5-羟色胺能受体拮抗剂,赛庚啶,非选择性毒蕈碱乙酰胆碱受体拮抗剂,阿托品,a D(2),D(3),D(4) 多巴胺受体拮抗剂,氟哌啶醇,或 γ-氨基丁酸亚基a受体拮抗剂,双小分子。FST显示,kisspeptin-13逆转了不动,攀爬和游泳时间,暗示了类似抗抑郁药的作用。苯氧基苯甲胺,育亨宾和赛庚啶阻止了kisspeptin-13对不动,攀爬和游泳时间的影响,而哌唑嗪,普萘洛尔,甲基sergide,阿托品,氟哌啶醇和双核苷不能改变kisspeptin-13的影响。结果表明,kisspeptin-13在改良小鼠FST中的抗抑郁药样作用至少部分由 α(2)-肾上腺素能和5-HT(2) 血清素能受体的相互作用介导。
  • 【多巴胺在抗抑郁药物作用机制中的作用。】 复制标题 收藏 收藏
    DOI:10.1016/s0014-2999(00)00566-5 复制DOI
    作者列表:D'Aquila PS,Collu M,Gessa GL,Serra G
    BACKGROUND & AIMS: :The present paper reviews evidence on the effect of antidepressant treatments on dopamine transmission. Chronic treatment with antidepressant drugs potentiates the behavioural stimulant responses elicited by the stimulation of dopamine receptors, including reward-related behaviours. Moreover, antidepressants affect dopamine release in several brain areas. The reviewed literature is discussed in terms of the possible mechanisms underlying antidepressant-induced supersensitivity to dopamine-mediated behavioural responses, and of the possible implications for the therapeutic effect of these drugs. It is concluded that the potentiation of dopaminergic neurotransmission induced by chronic antidepressant treatments might contribute to their therapeutic effect.
    背景与目标: : 本文回顾了抗抑郁药治疗对多巴胺传播影响的证据。抗抑郁药物的长期治疗增强了多巴胺受体刺激引起的行为刺激反应,包括奖励相关行为。此外,抗抑郁药会影响几个大脑区域的多巴胺释放。讨论了抗抑郁药诱导的对多巴胺介导的行为反应超敏的可能机制,以及对这些药物的治疗作用的可能影响。结论是,慢性抗抑郁药治疗引起的多巴胺能神经传递的增强可能有助于其治疗效果。
  • 【单胺能系统参与小鼠纹状体水提取物的抗抑郁样作用。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Saleem AM,Taufik Hidayat M,Jais AM,Fakurazi S,Moklas MA,Sulaiman MR,Amom Z,Basir R
    BACKGROUND & AIMS: BACKGROUND:In our previous study, the aqueous extract of Channa striatus (family: Channidae) fillet (AECSF) showed an antidepressant-like effect in mice. However, the mechanism of the antidepressant-like effect is unknown. AIM:The objective of this study was to explore the involvement of monoamines in the antidepressant-like effect of AECSF in mice. MATERIALS AND METHODS:AECSF was prepared by steaming the fillets of C. striatus. The male ICR mice were pretreated with various monoaminergic antagonists viz., p-chlorophenylalanine (100 mg/kg, i.p.), prazosin (1 mg/kg, i.p.) and yohimbine (1 mg/kg, i.p.), SCH23390 (0.05 mg/kg, s.c.) and sulpiride (50 mg/kg, i.p.) followed by treatment with AECSF and tested in tail suspension test (TST). Two-way ANOVA with Tukey test were used at p < 0.05 for significance. RESULTS:The pretreatments with p-chlorophenylalanine, prazosin and yohimbine, but not with SCH23390 and sulpiride, were able to reverse the antidepressant-like effect of AECSF in TST. CONCLUSIONS:The antidepressant-like effect of AECSF may be mediated through the serotonergic and noradrenergic systems and not through the dopaminergic system.
    背景与目标:
  • 【三环抗抑郁药阿米替林对HTB114人平滑肌肉瘤具有细胞毒性,并诱导p75(NTR) 依赖性凋亡。】 复制标题 收藏 收藏
    DOI:10.1097/CAD.0b013e328364312f 复制DOI
    作者列表:Pula G,Pistilli A,Montagnoli C,Stabile AM,Rambotti MG,Rende M
    BACKGROUND & AIMS: :Nerve growth factor (NGF) receptors, TrKA and p75(NTR), are being investigated in cancer therapy. Our previous data show that, in HTB114 uterine leiomyosarcoma cells, p75(NTR)-dependent apoptosis is inducible by cytotoxic drugs and can suppress nerve growth factor-dependent growth. Although amitriptyline can kill cancer cells and bind TrKA/B, its effects on p75-dependent apoptosis are unknown. The aim of this paper was to evaluate the antineoplastic potential of amitriptyline, and the role of p75(NTR)-dependent apoptosis in the chemoresistant uterine HTB114 leiomyosarcoma. Using proliferation assays and fluorescence-activated cell sorting analysis, we found that amitriptyline caused a marked reduction in HTB114 cell viability, associated with the parallel upregulation of p75(NTR) expression. This converted the TrKA⁺-proliferating cells into TrKA⁺/p75(NTR⁺), leading to downregulation of TrKA-prosurvival signaling (AKT) and activation of p75(NTR)-dependent apoptosis (through caspase-3). Overall, we provide novel evidence that HTB114 uterine leiomyosarcoma cells are highly sensitive to amitriptyline, supporting the role of p75(NTR)-dependent apoptosis as a novel cytotoxic mechanism of this drug and of p75(NTR) as an inducible stress receptor and a novel target in clinical oncology.
    背景与目标: : 神经生长因子 (NGF) 受体TrKA和p75(NTR) 正在癌症治疗中进行研究。我们以前的数据表明,在HTB114子宫平滑肌肉瘤细胞中,细胞毒性药物可诱导p75(NTR) 依赖性凋亡,并可以抑制神经生长因子依赖性生长。尽管阿米替林可以杀死癌细胞并结合TrKA/B,但其对p75-dependent凋亡的影响尚不清楚。本文的目的是评估阿米替林的抗肿瘤潜力,以及p75(NTR) 依赖性凋亡在化学抗性子宫HTB114平滑肌肉瘤中的作用。使用增殖测定和荧光激活的细胞分选分析,我们发现阿米替林导致HTB114细胞活力显着降低,与p75(NTR) 表达的平行上调有关。这将TrKA + 增殖细胞转化为TrKA +/p75(NTR +),导致TrKA-前生存信号 (AKT) 的下调和p75(NTR) 依赖性细胞凋亡的激活 (通过caspase-3)。总体而言,我们提供了新的证据,表明HTB114子宫平滑肌肉瘤细胞对阿米替林高度敏感,支持p75(NTR) 依赖性凋亡作为该药物的新型细胞毒性机制的作用,以及p75(NTR) 作为可诱导的应激受体的作用。临床肿瘤学的新靶标。
  • 【农村养老院居民抑郁症的抗抑郁治疗。】 复制标题 收藏 收藏
    DOI:10.1080/01612840802274651 复制DOI
    作者列表:Kerber CS,Dyck MJ,Culp KR,Buckwalter K
    BACKGROUND & AIMS: :Under-diagnosis and under-treatment of depression are major problems in nursing home residents. The purpose of this study was to determine antidepressant use among nursing home residents who were diagnosed with depression using three different methods: (1) the Geriatric Depression Scale, (2) Minimum Data Set, and (3) primary care provider assessments. As one would expect, the odds of being treated with an antidepressant were about eight times higher for those diagnosed as depressed by the primary care provider compared to the Geriatric Depression Scale or the Minimum Data Set. Men were less likely to be diagnosed and treated with antidepressants by their primary care provider than women. Depression detected by nurses through the Minimum Data Set was treated at a lower rate with antidepressants, which generates issues related to interprofessional communication, nursing staff communication, and the need for geropsychiatric role models in nursing homes.
    背景与目标: : 抑郁症的诊断不足和治疗不足是疗养院居民的主要问题。这项研究的目的是确定使用三种不同方法诊断为抑郁症的疗养院居民中的抗抑郁药使用 :( 1) 老年抑郁量表,(2) 最小数据集,以及 (3) 初级保健提供者评估。正如人们所期望的那样,与老年抑郁症量表或最低数据集相比,初级保健提供者诊断为抑郁症的人接受抗抑郁药治疗的几率大约是抑郁症的八倍。与女性相比,男性被初级保健提供者诊断和治疗抗抑郁药的可能性较小。护士通过最低数据集检测到的抑郁症,使用抗抑郁药以较低的比率进行治疗,这会产生与专业间沟通,护理人员沟通以及在疗养院中需要老年儿童榜样有关的问题。
  • 【DNA甲基化与抗抑郁药物的关系: 系统评价。】 复制标题 收藏 收藏
    DOI:10.3390/ijms21030826 复制DOI
    作者列表:Webb LM,Phillips KE,Ho MC,Veldic M,Blacker CJ
    BACKGROUND & AIMS: :Major depressive disorder (MDD) is the leading cause of disability worldwide and is associated with high rates of suicide and medical comorbidities. Current antidepressant medications are suboptimal, as most MDD patients fail to achieve complete remission from symptoms. At present, clinicians are unable to predict which antidepressant is most effective for a particular patient, exposing patients to multiple medication trials and side effects. Since MDD's etiology includes interactions between genes and environment, the epigenome is of interest for predictive utility and treatment monitoring. Epigenetic mechanisms of antidepressant medications are incompletely understood. Differences in epigenetic profiles may impact treatment response. A systematic literature search yielded 24 studies reporting the interaction between antidepressants and eight genes (BDNF, MAOA, SLC6A2, SLC6A4, HTR1A, HTR1B, IL6, IL11) and whole genome methylation. Methylation of certain sites within BDNF, SLC6A4, HTR1A, HTR1B, IL11, and the whole genome was predictive of antidepressant response. Comparing DNA methylation in patients during depressive episodes, during treatment, in remission, and after antidepressant cessation would help clarify the influence of antidepressant medications on DNA methylation. Individuals' unique methylation profiles may be used clinically for personalization of antidepressant choice in the future.
    背景与目标: : 重度抑郁症 (MDD) 是全球残疾的主要原因,与自杀和医疗合并症的高发生率有关。当前的抗抑郁药物是次优的,因为大多数MDD患者无法完全缓解症状。目前,临床医生无法预测哪种抗抑郁药对特定患者最有效,使患者暴露于多种药物试验和副作用。由于MDD的病因包括基因与环境之间的相互作用,因此表观基因组对于预测效用和治疗监测很有意义。抗抑郁药物的表观遗传机制尚不完全清楚。表观遗传谱的差异可能会影响治疗反应。系统的文献搜索产生了24项研究,报告了抗抑郁药与八个基因 (BDNF,MAOA,SLC6A2,SLC6A4,HTR1A,HTR1B,IL6,IL11) 和全基因组甲基化之间的相互作用。BDNF,SLC6A4,HTR1A,HTR1B,IL11和全基因组中某些位点的甲基化可预测抗抑郁反应。在抑郁发作期间,治疗期间,缓解期间以及抗抑郁药停止后比较患者的DNA甲基化将有助于阐明抗抑郁药物对DNA甲基化的影响。个人独特的甲基化谱将来可能会在临床上用于个性化抗抑郁药的选择。
  • 【新生去甲肾上腺素能神经元损伤后成年大鼠5-HT1A受体的反应性 -- 对抗抑郁药样作用的影响。】 复制标题 收藏 收藏
    DOI:10.1016/j.brainres.2008.08.054 复制DOI
    作者列表:Dabrowska J,Nowak P,Brus R
    BACKGROUND & AIMS: :The aim of this study was to assess the 5-HT1A receptor reactivity after neonatal noradrenergic neurons' lesion. DSP-4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine), 50 mg/kg, was administered 30 min after a selective serotonin reuptake inhibitor (SSRI)--zimelidine (10 mg/kg) on the 1st and 3rd day of life. Zimelidine was used to prevent serotonin (5-HT) depletion. 5-HT1A autoreceptor is involved in the regulation of 5-HT release as well as the pathogenesis of depression. During a microdialysis study of anaesthetized rats, the 5-HT1A receptor agonist, R-(+)-8-OH-DPAT (0.1 mg/kg), decreased 5-HT release in the medial prefrontal cortex of control rats but this effect was significantly attenuated in DSP-4-treated animals (10-12 weeks old). To further determine which type of receptor, either pre or postsynaptically located, is involved in the attenuated response to the 5-HT1A receptor agonist in lesioned rats, behavioral tests were conducted. In the forced swimming test, DSP-4 treated rats after saline injection, displayed shorter immobility time in comparison to control rats. R-(+)-8-OH-DPAT (0.5 mg/kg) evoked an antidepressant-like effect in control and DSP-4 treated rats in a learned helplessness paradigm as well as the forced swimming test. The results of this study provided further support for the exclusive desensitization of 5-HT1A autoreceptor in adult rats with neonatal lesion of the central noradrenergic system.
    背景与目标: : 这项研究的目的是评估新生儿去甲肾上腺素能神经元病变后的5-HT1A受体反应性。在生命的第1天和第3天,在选择性5-羟色胺再摄取抑制剂 (SSRI)-齐美利定 (10 mg/kg) 后30分钟施用DSP-4 (N-(2-氯乙基)-N-ethyl-2-bromobenzylamine) 50 mg/kg。Zimelidine用于防止5-羟色胺 (5-HT) 消耗。5-HT1A自身受体参与5-HT释放的调节以及抑郁症的发病机理。在麻醉大鼠的微透析研究中,5-HT1A受体激动剂R-()-8-OH-DPAT (0.1 mg/kg) 降低了对照大鼠内侧前额叶皮层的5-HT释放,但这种作用在DSP-4-treated动物 (10-12周龄) 中明显减弱。为了进一步确定哪种类型的受体 (位于突触前或突触后) 参与受损大鼠对5-HT1A受体激动剂的减弱反应,进行了行为测试。在强迫游泳试验中,与对照大鼠相比,注射盐水后DSP-4处理的大鼠显示出更短的不动时间。R-()-8-OH-DPAT (0.5 mg/kg) 在习得的无助范式和强迫游泳测试中,在对照和DSP-4治疗的大鼠中引起了抗抑郁药样作用。这项研究的结果为中枢去甲肾上腺素能系统新生损伤的成年大鼠中5-HT1A自身受体的排他性脱敏提供了进一步的支持。
  • 【5-HT1A受体激活和抗抑郁样作用: F 13714具有很高的功效和明显的抗抑郁潜力。】 复制标题 收藏 收藏
    DOI:10.1016/s0014-2999(01)01011-1 复制DOI
    作者列表:Koek W,Vacher B,Cosi C,Assié MB,Patoiseau JF,Pauwels PJ,Colpaert FC
    BACKGROUND & AIMS: :To examine further the hypothesis that the magnitude of the intrinsic activity of agonists at 5-HT1A receptors determines the magnitude of their psychotropic activity, we studied the relationship between the maximal receptor activation produced by various 5-HT1A receptor ligands and their antidepressant-like effects (i.e., decreased immobility in the forced swimming test in rats). Using three different in vitro assays suitable to measure differences among high, intermediate, and low efficacy 5-HT1A receptor agonists, ligands were identified with intrinsic activities ranging from low-negative (i.e., the inverse agonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexane-carboxamide (WAY 100635)) to high-positive (i.e., 3-chloro-4-fluorophenyl-(4-fluoro-4-[[(5-methyl-6-methylamino-pyridin-2-ylmethyl)-amino]-methyl]-piperidin-1-yl-methanone (F 13714)). In addition, novel compounds with intermediate intrinsic activity, like buspirone, but with high selectivity for 5-HT1A receptors, unlike buspirone, were identified. The maximal effects of the 5-HT1A receptor ligands in the forced swimming test correlated positively (rS=0.91, P<0.005) with the rank order of their intrinsic activity at 5-HT1A receptors. This relationship constitutes evidence that the magnitude of the psychotropic activity of 5-HT1A receptor ligands is a positive function of their intrinsic activity at the receptor, and suggests that F 13714, which had maximal effects in the forced swimming test significantly larger than any of the other compounds examined here, did so because of its higher intrinsic activity at 5-HT1A receptors.
    背景与目标: : 为了进一步研究以下假设: 激动剂在5-HT1A受体上的内在活性大小决定了其精神活性的大小,我们研究了各种5-HT1A受体配体产生的最大受体激活与其抗抑郁药之间的关系-样作用 (即,大鼠强制游泳试验中的不动度降低)。使用适用于测量高,中和低功效5-HT1A受体激动剂之间差异的三种不同的体外测定法,鉴定出配体的内在活性范围为低阴性 (即,反向激动剂N-[2-[4-(2-甲氧基苯基)-1-哌嗪基] 乙基]-N-(2-吡啶基) 环己烷-甲酰胺 (路100635)) 至高阳性 (即,3-氯-4-氟苯基-(4-氟-4-[[(5-甲基-6-甲基氨基-吡啶-2-基甲基)-氨基]-甲基]-piperidin-1-yl-methanone (F 13714)。此外,具有中间固有活性的新化合物,如丁螺环酮,但对5-HT1A受体具有高选择性,与丁螺环酮不同,5-ht1a受体配体在强迫游泳试验中的最大作用呈正相关 (rS = 0.91,P<0.005),其在5-HT1A受体上的内在活性的等级顺序。这种关系证明5-HT1A受体配体的精神活性的大小是其在受体上内在活性的正向功能,并表明F 13714,在强迫游泳测试中具有最大作用的效果明显大于此处检查的任何其他化合物,之所以这样做是因为它在5-HT1A受体上具有更高的内在活性。
  • 【GSK-3: 增强AMPA对NMDA通量介导氯胺酮快速抗抑郁作用的关键调控靶点。】 复制标题 收藏 收藏
    DOI:10.1111/bdi.12452 复制DOI
    作者列表:Zarate CA Jr,Machado-Vieira R
    BACKGROUND & AIMS: -2
    背景与目标: -2
  • 【芥酸酰胺 (一种生物活性脂肪酸酰胺) 的抗抑郁和抗焦虑样行为作用,涉及小鼠的下丘脑-垂体-肾上腺轴。】 复制标题 收藏 收藏
    DOI:10.1016/j.neulet.2016.12.072 复制DOI
    作者列表:Li MM,Jiang ZE,Song LY,Quan ZS,Yu HL
    BACKGROUND & AIMS: :Erucamide (Era) is a bioactive fatty acid amide, which is similar to the classical endocannabinoid analogue oleoylethanolamide (OEA). In the present study, we hypothesized that Era may regulate the central nervous system and may have the potential to antagonize depression and anxiety. Therefore, we investigated the antidepressant and anxiolytic effects of Era in animal models in comparison with fluoxetine (Fxt). Fifty mice were randomly divided into 5 groups, and treated with a vehicle (0.3% methyl cellulose, 20mL/kg, p.o.), Era (5, 10, 20mg/kg, p.o.), or Fxt (20mg/kg, p.o.) for 7days. Immobility was used to evaluate depressive-like behavior in the forced swimming test (FST) and tail suspension test (TST). Animal activity and exploratory behavior as well as anxiety-like behaviors were measured in open field test (OFT) and elevated plus-maze test (EPMT) in mice. Additionally, serum adrenocorticotrophic hormone (ACTH) and corticosterone (CORT) levels were determined using the ELISA method, and the total anti-oxidative capacity (T-AOC) was detected by ultraviolet spectrophotometry. Our data showed that Era (5, 10, or 20mg/kg) induced a significant reduction in mouse immobility time in the TST and FST compared to the normal control group (vehicle group). The positive control, Fxt (20mg/kg group), also induced a significant change in immobility time in the TST and FST compared to the control (vehicle) group. In the OFT, compared with the control group, Fxt (20mg/kg) and Era (5, 10, or 20mg/kg) did not significantly change the locomotive activity (locomotive time, immobility time, or locomotive distance) in mice, but Fxt (20mg/kg) and Era (10, or 20mg/kg) significantly increased the percentage of time spent and squares visited in the OFT central area. In regards to the EPMT, the data showed that Fxt (20mg/kg) and Era (10, 20mg/kg) significantly increased the ratio of time spent and entries in open arms, but did not significantly change the total locomotive distance (including open arms and closed arms) compared to the control group. Biochemical tests found that after 7days of drug treatment, compared with the control group, ACTH and CORT serum levels in mice were significantly decreased, although T-AOC levels did not significantly change. In conclusion, Era (dose range of 5-20mg/kg) administered orally may alleviate depression- and anxiety-like behaviors in mice, and the antidepressant and anti-anxiety effects of Era may be related to the regulation of the hypothalamus-pituitary-adrenal axis (HPA).
    背景与目标: : 芥酸酰胺 (Era) 是一种生物活性脂肪酸酰胺,类似于经典的内源性大麻素类似物油酰乙醇酰胺 (OEA)。在本研究中,我们假设Era可能调节中枢神经系统,并且可能具有对抗抑郁和焦虑的潜力。因此,我们与氟西汀 (Fxt) 相比,研究了Era在动物模型中的抗抑郁和抗焦虑作用。将50只小鼠随机分为5组,用赋形剂 (0.3% 甲基纤维素,20ml/kg,p.o.) 、Era (5,10,20 mg/kg,p.o.) 或Fxt (20 mg/kg,p.o.) 处理7天。在强迫游泳测试 (FST) 和尾部悬挂测试 (TST) 中,使用不动来评估类似抑郁的行为。在小鼠的野外试验 (OFT) 和高架迷宫试验 (EPMT) 中测量了动物的活动和探索行为以及焦虑样行为。此外,采用ELISA法测定血清促肾上腺皮质激素 (ACTH) 和皮质酮 (CORT) 水平,并通过紫外分光光度法检测总抗氧化能力 (t-aoc)。我们的数据显示,与正常对照组 (媒介物组) 相比,Era (5、10或20 mg/kg) 在TST和FST中诱导小鼠不动时间显着减少。与对照组 (赋形体) 相比,阳性对照Fxt (20 mg/kg组) 在TST和FST中也引起了不动时间的显着变化。在OFT中,与对照组相比,Fxt (20 mg/kg) 和Era (5、10或20 mg/kg) 并未显着改变小鼠的机车活动 (机车时间,不动时间或机车距离),但Fxt (20 mg/kg) 和Era (10,或20 mg/kg) 显着增加了OFT中心区域花费时间和访问广场的百分比。关于EPMT,数据显示,Fxt (20 mg/kg) 和Era (10,20 mg/kg) 显着增加了张开臂所花费的时间和进入的比率,但并未显着改变总机车距离 (包括张开臂和闭合臂) 与对照组相比。生化测试发现,药物治疗7天后,与对照组相比,小鼠ACTH和CORT血清水平明显降低,尽管t-aoc水平没有明显变化。总之,口服Era (剂量范围为5-20 mg/kg) 可以减轻小鼠的抑郁和焦虑样行为,Era的抗抑郁和抗焦虑作用可能与下丘脑-垂体-肾上腺轴 (HPA) 的调节有关。
  • 【认知行为疗法对抗抑郁药物的量化优势: 对早期荟萃分析的挑战。】 复制标题 收藏 收藏
    DOI:10.1111/j.1600-0447.2008.01196.x 复制DOI
    作者列表:Parker GB,Crawford J,Hadzi-Pavlovic D
    BACKGROUND & AIMS: OBJECTIVE:The study aimed to review the conclusion of a previously published meta-analysis which quantified distinct superiority of cognitive therapy to antidepressant drug-therapy (P < 0.0001). METHOD:We sought to include all studies used in the original meta-analysis. Adopting both that study's inclusion criteria and additional criteria resulted in a reduced set of studies. We analysed both 'completer' and 'intention to treat' data, using effect size and odds ratio quantification. RESULTS:There was an overall trend for cognitive therapy to be superior to antidepressant drug-therapy, but this was significant for only one of the four meta-analyses (an intention to treat analysis). We demonstrated considerable heterogeneity between studies, and a significantly higher drop-out rate in the antidepressant groups. CONCLUSION:The previous interpretation--cognitive therapy being distinctly superior to antidepressant medication--cannot be sustained from the currently analysed data set.
    背景与目标:
  • 【慢性抗抑郁药治疗对大鼠大脑皮层中Gs和Gi α 亚基蛋白和mRNA水平缺乏影响。】 复制标题 收藏 收藏
    DOI:10.1016/0893-133X(95)00211-U 复制DOI
    作者列表:Emamghoreishi M,Warsh JJ,Sibony D,Li PP
    BACKGROUND & AIMS: Experimental evidence indicates that chronic antidepressant treatment in rats modifies the central nervous system beta-adrenoceptor signaling pathway at multiple sites including receptor, G-protein, adenylyl cyclase, and protein kinase A. In the present study, we examined the postreceptor effect of antidepressant treatment on the protein and mRNA levels of stimulatory and inhibitory C protein alpha-subunits (G alpha s and G alpha i) and beta-subunits in rats infused continuously with various antidepressants for 21 days. Chronic treatment with tricylic (desipramine and amitriptyline) and monoamine oxidase inhibiting (tranylcypromine) antidepressants did not significantly affect the immunoreactivity levels of G alpha s (both 45- and 52-kDa species), G alpha i1, G alpha i2, G beta 36, and beta 35 in rat cerebral cortex. Similarly, the levels of mRNA encoding these G protein subunits remained unchanged subsequent to these drug treatments. In contrast, cortical beta-adrenoceptor number was significantly decreased by these treatments. These results suggest that the adaptive changes of rat cerebral cortical beta-adrenoceptor-adenylyl cyclase system often seen after chronic antidepressant treatment are not accompanied by changes in the abundance and gene expression of G alpha s, G alpha i, or G beta proteins.

    背景与目标: 实验证据表明,在大鼠中进行慢性抗抑郁治疗会在多个部位 (包括受体,g蛋白,腺苷酸环化酶和蛋白激酶A) 改变中枢神经系统 β-肾上腺素受体信号通路。在本研究中,我们检查了抗抑郁药治疗对连续输注各种抗抑郁药的大鼠的刺激性和抑制性C蛋白 α 亚基 (G α s和G α i) 和 β 亚基的蛋白质和mRNA水平的受体后作用。持续21天。用三环 (地昔帕明和阿米替林) 和单胺氧化酶抑制 (反环丙胺) 抗抑郁药进行慢性治疗不会显着影响G alpha s (45和52 kDa物种),G alpha i1,G alpha i2的免疫反应性水平,gβ36和 β35在大鼠大脑皮层中。同样,在这些药物治疗后,编码这些g蛋白亚基的mRNA水平保持不变。相反,通过这些治疗,皮质 β-肾上腺素受体的数量显着减少。这些结果表明,慢性抗抑郁药治疗后经常看到的大鼠大脑皮层 β-肾上腺素受体-腺苷酸环化酶系统的适应性变化并不伴随G α s,G α i或G β 蛋白的丰度和基因表达的变化。
  • 【民航中抗抑郁药的使用和安全性: 一项针对澳大利亚10年数据的病例对照研究。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Ross J,Griffiths K,Dear K,Emonson D,Lambeth L
    BACKGROUND & AIMS: OBJECTIVES:Australian aviation medical certification authorities began allowing use of antidepressant medications by aviation personnel in 1987; a sufficiently long period of time and number of personnel involved to allow a preliminary study. The aim of this study was to identify significant safety-related outcomes, such as aircraft accidents or incidents that may be related to the use of antidepressant medication in pilots and air traffic controllers. METHODS:The study employed a matched cohort of all holders of Australian aviation medical certificates who were prescribed antidepressants during the period 1 January 1993 to 30 June 2004 (n = 481), and a matched comparison group. Outcomes of interest were accidents and incidents. RESULTS:No significant differences between the two groups were found in any of the analyses. There were 18 accidents recorded for the antidepressant group and 15 for the comparison group across the whole period, compared with 5 for cases and 5 for controls during the period while antidepressants were being taken. There were 113 incidents recorded for the antidepressant group compared with 131 controls. A non-significantly higher number of accidents and incidents were recorded among cases in the period prior to commencing antidepressant medication. CONCLUSION:This study found no evidence of adverse safety outcomes arising from permitting individuals to operate as commercial or private aircrew or air traffic controllers while using antidepressants provided specific criteria are met and maintained. This finding has the potential to change current policies of aviation regulatory bodies internationally and may be of significance to a range of transport and other safety-critical occupations and activities.
    背景与目标:

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