Multiple Organolithium Generation in the Continuous Flow Synthesis of Amitriptyline

A continuous flow protocol for the preparation of the tricyclic antidepressant (TCA) amitriptyline is reported. The advantages of flow chemistry when handling organometallic agents as well as when performing reaction with gases are demonstrated. Continuous multilithiation combined with carboxylation and the Parham cyclization, a Grignard addition and thermolytic water elimination by inductive heating are key features of the multistep protocol.

     

龙牙草石油醚提取物中的挥发成分研究

为探讨龙牙草在石油醚中的溶解成分,利用索氏提取器获取了龙牙草石油醚提取物,并利用气相色谱-质谱(GC - MS)联用技术对其进行了分析.研究显示:龙牙草石油醚提取物的收率为3.20%; 在龙牙草石油醚提取物的35个强色谱峰中共鉴定出27个成分,占石油醚提取物总含量的45.28%.27个成分中相对百分含量较高的成分依次为三环[3,5,7]癸烷 -1- 羧酸辛酯(6.42%)、胆酸乙酯(3.87%)、棕榈酸(3.67%)、(E)- 3,7,11,15- 四甲基十六醇 -2- 烯 -1- 醇(3.37%)、α- 姜黄烯(2.93%)、绵马素(2.15%)等.该结果可为龙牙草的药理研究和开发利用提供参考.     

Genetic Background Underlying 5-HT1A Receptor Functioning Affects the Response to Fluoxetine

The influence of genetic background on sensitivity to drugs represents a topical problem of personalized medicine. Here, we investigated the effect of chronic (20 mg/kg, 14 days, i.p.) antidepressant fluoxetine treatment on recombinant B6-M76C mice, differed from control B6-M76B mice by CBA-derived 102.73–110.56 Mbp fragment of chromosome 13 and characterized by altered sensitivity of 5-HT_1A receptors to chronic 8-OH-DPAT administration and higher 5-HT_1A receptor mRNA levels in the frontal cortex and hippocampus. Significant changes in the effects of fluoxetine treatment on behavior and brain 5-HT system in recombinant B6-M76C mice were revealed. In contrast to B6-M76B mice, in B6-M76C mice, fluoxetine produced pro-depressive effects, assessed in a forced swim test. Fluoxetine decreased 5-HT_1A receptor mRNA levels in the cortex and hippocampus, reduced 5-HT_1A receptor protein levels and increased receptor silencer Freud-1 protein levels in the hippocampus of B6-M76C mice. Fluoxetine increased mRNA levels of the gene encoding key enzyme for 5-HT synthesis in the brain, tryptophan hydroxylase-2, but decreased tryptophan hydroxylase-2 protein levels in the midbrain of B6-M76B mice. These changes were accompanied by increased expression of the 5-HT transporter gene. Fluoxetine reduced 5-HT and 5-HIAA levels in cortex, hippocampus and midbrain of B6-M76B and in cortex and midbrain of B6-M76C; mice. These data demonstrate that changes in genetic background may have a dramatic effect on sensitivity to classic antidepressants from the Selective Serotonin Reuptake Inhibitors family. Additionally, the results provide new evidence confirming our idea on the disrupted functioning of 5-HT_1A autoreceptors in the brains of B6-M76C mice, suggesting these mice as a model of antidepressant resistance.     

Prescriptive authority in the face of research revelations.

Fox and his colleagues (May–June 2009) listed three occurrences beginning in the 1980s that have dampened psychologists’ desires to procure the right to prescribe psychotropic medications. That research review highlighted the fact that antidepressants produce a very modest effect at best when compared with placebos. I briefly summarize here some of the important findings that emerged from our original survey and two more recent reviews (Greenberg & Davis Goldman, 2009; Greenberg & Fisher, 1997). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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.     

NaH催化合成3,4-二氢-2H-吡嗪并[2,1-b]喹唑啉-1,6-二酮及其抗肝癌细胞活性评价

以邻氨基苯甲酰胺(5)为原料,依次经分子间环合、烷基化、氨解和分子内环合四步反应成功合成目标化合物3,4-二氢-2H-吡嗪并[2,1-b]喹唑啉-1,6-二酮(10),总收率为46. 5%,其中,中间体(8)、(9)及目标化合物(10)均未见文献报道,其结构经~1H NMR和MS(ESI)确证,并采用MTT法初步评价目标化合物的体外抗肝癌活性。结果表明,3,4-二氢-2H-吡嗪并[2,1-b]喹唑啉-1,6-二酮对SMMC-7721具有明显的抑制活性,优于阳性对照药舒尼替尼,可为进一步发现新型抗肝癌药物提供先导结构,也为该类衍生物的大量合成和结构改造提供参考方法。     

含降冰片烯多脂环化合物在高聚物上的应用

综述了含降冰片烯多脂环化合物的合成及其在配位络合聚合、环烯烃开环聚合、（ 甲基） 丙烯酸多脂环（ 氧烷基） 酯与（ 甲基） 丙烯酸多脂环烯（ 氧烷基） 酯合成方面的应用; 并介绍了用它合成的一系列高聚物的性质和应用。     

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)