快眼动睡眠调节机制及影响药物

探究快眼动（rapid eye movement,REM）睡眠调节机制及影响药物。本文从调控REM睡眠的神经环路出发，总结了脑桥、延髓、下丘脑中调控REM睡眠的相关核团，并且归纳了各类影响REM睡眠的药物，例如：选择性去甲肾上腺素再摄取抑制剂和选择性5-羟色胺（5-hydroxytryptamine,5-HT）再摄取抑制剂等，其作用机制可归纳为减少突触部位去甲肾上腺素、5-HT的降解，延长神经递质的作用时间；减少突触前膜再摄取，使突触间隙中递质作用时间延长, 相对提高去甲肾上腺素、5-HT神经元的兴奋性。     

抗抑郁药种类概述及发展趋势

随着抑郁症患者的日益增加，抗抑郁药面临着一个巨大的市场空间。从抗抑郁药作用机理和性质入手，综合阐述了抗抑郁药的种类与作用，并对其目前情况和发展趋势进行了详细的报道。     

Synthesis of Novel Pyrido[1,2-c]pyrimidine Derivatives with 6-Fluoro-3-(4-piperidynyl)-1,2-benzisoxazole Moiety as Potential SSRI and 5-HT1A Receptor Ligands

Two series of novel 4-aryl-2H-pyrido[1,2-c]pyrimidine (6a–i) and 4-aryl-5,6,7,8-tetrahydropyrido[1,2-c]pyrimidine (7a–i) derivatives were synthesized. The chemical structures of the new compounds were confirmed by ¹H and ¹³C NMR spectroscopy and ESI-HRMS spectrometry. The affinities of all compounds for the 5-HT_1A receptor and serotonin transporter protein (SERT) were determined by in vitro radioligand binding assays. The test compounds demonstrated very high binding affinities for the 5-HT_1A receptor of all derivatives in the series (6a–i and 7a–i) and generally low binding affinities for the SERT protein, with the exception of compounds 6a and 7g. Extended affinity tests for the receptors D₂, 5-HT_2A, 5-HT₆ and 5-HT₇ were conducted with regard to selected compounds (6a, 7g, 6d and 7i). All four compounds demonstrated very high affinities for the D₂ and 5-HT_2A receptors. Compounds 6a and 7g also had high affinities for 5-HT₇, while 6d and 7i held moderate affinities for this receptor. Compounds 6a and 7g were also tested in vivo to identify their functional activity profiles with regard to the 5-HT_1A receptor, with 6a demonstrating the activity profile of a presynaptic agonist. Metabolic stability tests were also conducted for 6a and 6d.     

A time to consider health care reform: A reply to Rudd, Cordero, and Bryan.

The author questions the premise on which the M. D. Rudd, L. Cordero, and C. J. Bryan (see record 2009-11890-001) argument is based and delineates some of the risks of psychotropic medication for children and adolescents. The argument is made that the diagnosis of depression should be made by specialty care providers who have particular expertise pertaining to specific developmental issues of children and adolescents. Recommendations are made for the development of psychosocial interventions for children and adolescents that may prove efficacious for the management of depression in children and adolescents. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Posttraumatic stress disorder arising after road traffic collisions: Patterns of response to cognitive–behavior therapy.

Road traffic collisions (RTCs) are common precipitants of posttraumatic stress disorder (PTSD). Two preliminary studies suggest that cognitive–behavior therapy (CBT) is, on average, effective in treating this disorder, although the major patterns of treatment outcome remain to be identified. Such outcomes might include treatment response, partial response, and response followed by relapse. To identify these patterns, 50 people with RTC-PTSD completed a 12-week course of CBT, with outcome assessment extending to 3-month follow up. Dynamic cluster analyses revealed 2 replicable patterns of outcome: one for responders (n?=?30) and one for partial responders (n?=?20). Partial responders, compared with responders, tended to have more severe pretreatment numbing symptoms and greater anger about their RTC, along with lower global levels of functioning, greater pain severity and interference, and greater depression and were more likely to be taking psychotropic medications. Responders and partial responders did not differ in homework adherence, number of sessions attended, therapist effects, or stressors occurring during therapy or in the presence or absence of RTC-related litigation. Implications for enhancing treatment outcome are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

抗抑郁药的信号转导机制

抗抑郁药的作用机制目前尚不明确, 传统单胺递质理论和受体理论都不能充分解释抗抑郁药的临床效应滞后现象。近年提出抗抑郁药的信号转导机制, 认为抗抑郁药是以G 蛋白为分子基础, 神经递质受体和G 蛋白为作用环节, 最终影响细胞内的信号转导并产生磷酸化作用增加、神经营养因子增多、神经发生增加等相关效应, 从而发挥抗抑郁作用。影响细胞内信号转导并产生相关效应需要的时间, 与抗抑郁药的临床效应滞后时间相吻合, 从而使抗抑郁药的滞后现象有了合理解释。这个机制的提出有助于抗抑郁新药的发展, 为研制安全、有效的新药指明了方向, 同时也为抑郁症生物学病因的阐明提供了必要信息。     

Effects of Antidepressants on IP-10 Production in LPS-Activated THP-1 Human Monocytes

Major depressive disorder and cardiovascular disease are common serious illnesses worldwide. Selective serotonin reuptake inhibitors and norepinephrine-dopamine reuptake inhibitors may reduce the mortality of cardiovascular disease patients with comorbid depression. Interferon-γ-inducible protein 10 (IP-10), a type 1 T helper cell (Th1)-related chemokine, contributes to manifestations of atherosclerosis during cardiovascular inflammations; however, the pathophysiological mechanisms linking cardiovascular disease and effective antidepressants have remained elusive. We investigated the in vitro effects of six different classes of antidepressants on the IP-10 chemokine expression in lipopolysaccharide (LPS)-stimulated monocytes, and their detailed intracellular mechanisms. The human monocytes were pretreated with antidepressants (10⁻⁸–10⁻⁵ M) before LPS-stimulation. IP-10 was measured by enzyme-linked immunosorbent assay (ELISA) and then intracellular signaling was investigated using Western blotting and chromatin immunoprecipitation. Fluoxetine and bupropion suppressed LPS-induced IP-10 expression in monocytes, and they had no cytotoxic effects. Furthermore, fluoxetine inhibited LPS-induced IP-10 expression via the mitogen-activated protein kinase (MAPK)-p38 pathway. Fluoxetine and bupropion could not only treat depression but also reduce Th1-related chemokine IP-10 production in human monocytes. Our results may indicate a possible mechanism related to how particular antidepressants reduce the risk of cardiovascular disease.     

HPLC-Q-TOF/MS测定保健食品中19种抗抑郁药物

目的：建立保健食品中非法添加19种抗抑郁药物的高效液相色谱—四极杆—飞行时间质谱快速筛查定性与定量分析方法。方法：样品采用甲醇溶液进行超声提取,提取液经C₁₈色谱柱分离,以0.1%甲酸水溶液—乙腈为流动相,梯度洗脱,在电喷雾正离子模式下进行检测,检测结果以试验方法建立的19种抗抑郁药物一级精确质量数据库和二级碎片质谱库进行筛查匹配。结果：在5～100 μg/L质量浓度范围内,19种目标化合物线性关系良好,相关系数为0.988 7~0.999 9,在2,5,10 μg/kg 3个加标水平下样品的回收率为81.2%～98.6%,相对标准偏差为0.9%～6.7%。结论：所建立的方法适用于保健食品中非法添加抗抑郁药物的快速筛查定性与定量分析。     

抗抑郁药度洛西汀的合成方法综述

抗抑郁药度洛西汀因其化学稳定、副作用小、药效明显优于其它抗抑郁药而具有广阔的发展前景,文章详细叙述了近年来国内外常见的几种合成方法,评述了各自优缺点,得出了一条最具竞争力的合成路线:以(S)-3-二甲胺基一1-2-噻吩基)-1-丙醇为原料,经拆分、醚化、酯化、水解得到目标。     

Trace Amine-Associated Receptor 1 Contributes to Diverse Functional Actions of O-Phenyl-Iodotyramine in Mice but Not to the Effects of Monoamine-Based Antidepressants

Trace Amine-Associated Receptor 1 (TAAR1) is a potential target for the treatment of depression and other CNS disorders. However, the precise functional roles of TAAR1 to the actions of clinically used antidepressants remains unclear. Herein, we addressed these issues employing the TAAR1 agonist, o-phenyl-iodotyramine (o-PIT), together with TAAR1-knockout (KO) mice. Irrespective of genotype, systemic administration of o-PIT led to a similar increase in mouse brain concentrations. Consistent with the observation of a high density of TAAR1 in the medial preoptic area, o-PIT-induced hypothermia was significantly reduced in TAAR1-KO mice. Furthermore, the inhibition of a prepulse inhibition response by o-PIT, as well as its induction of striatal tyrosine hydroxylase phosphorylation and elevation of extracellular DA in prefrontal cortex, were all reduced in TAAR1-KO compared to wildtype mice. O-PIT was active in both forced-swim and marble-burying tests, and its effects were significantly blunted in TAAR1-KO mice. Conversely, the actions on behaviour and prefrontal cortex dialysis of a broad suite of clinically used antidepressants were unaffected in TAAR1-KO mice. In conclusion, o-PIT is a useful tool for exploring the hypothermic and other functional antidepressant roles of TAAR1. By contrast, clinically used antidepressants do not require TAAR1 for expression of their antidepressant properties.