盐酸米多君的合成

以对苯二酚为原料，经酯化，重排，醚化，溴代，胺化，酰胺化，叠氮化，硼氢化钾／钯炭还原等8步反应合成盐酸米多君。还原反应改用成本较低的硼氢化钾，操作简单，条件温和。总收率15．1％。     

盐酸西布曲明的合成工艺改进

目的研究盐酸西布曲明适合工业化大生产的方法。方法以对氯氯苄为原料,经取代、环合、加成、还原、二甲基化及成盐等反应合成盐酸西布曲明,并对反应条件进行了改进和优化。结论工艺经改进和优化后,反应条件温和,操作简便,工艺稳定,总收率达到57.8%,大幅度的降低了生产成本,更加适合工业化生产。     

布美他尼的合成

以对氯苯甲酸为起始原料，经氯磺化、硝化、氨解、苯氧基化、还原和丁基化反应，合成利尿药布美他尼，总收率８．２％。所用原料价廉，反应条件温和，操作简便，产品质量符合中国药典。     

2-氯-4-氨基-6,7-二甲氧基喹唑啉的合成

目的合成2-氯-4-氨基-6,7-二甲氧基喹唑啉。方法以香草醛为原料,经甲基化、硝化、氧化、还原、环合、氯化、胺化等反应制得目标化合物。结果及结论该实验方法总收率26%,反应条件温和,操作简便,适合工业化生产。     

坎地沙坦酯的合成工艺改进

目的研究坎地沙坦酯的合成新方法,并对其工艺路线进行优化。方法以3-硝基邻苯二甲酸为原料,经过酯化、氯化、Curtius重排、脱Boc保护、还原、环合、水解、酯化、烃化、脱保护10步反应得到坎地沙坦酯。结果与结论该路线反应条件温和,原料廉价易得,同时避免了剧毒化合物烷基锡的使用,成本较低,总收率12.3%,适合工业化生产。     

舒马曲坦的合成

目的合成抗偏头痛药舒马曲坦。方法以对硝基氯苄为起始原料,经取代、胺化、还原、重氮化、环合等10步反应得到目标化合物舒马曲坦,总收率为18%。结果与结论目标化合物的结构经1H-NMR、IR和MS确证。该合成方法,反应条件温和,操作简便,原料易得,适合工业化生产。     

富马酸奈拉西坦的合成工艺研究

目的改进益智药富马酸奈拉西坦的合成工艺.方法以衣康酸二甲酯为起始原料,经Michael加成,分子内环合、还原、氯化、Gabriel反应及与富马酸成盐制得富马酸奈拉西坦.结果其结构经IR、MS、1H-NMR及元素分析确证,总收率为25%,比文献收率提高了15.4%.结论该合成工艺反应条件温和,易于操作,成本较低,较适合于工业化生产.     

盐酸氯普鲁卡因的合成

目的合成盐酸氯普鲁卡因并改进工艺。方法以2-氯-4-硝基苯甲酸为起始物料,经过还原、酯化、成盐3步反应制得盐酸氯普鲁卡因。结果目标物经IR、1H-NMR、13C-NMR和MS确证结构,反应总收率达到73.9%,纯度为99.76%。结论该合成路线操作简便、反应条件温和,适于工业化生产。     

盐酸奈福泮合成工艺的改进

目的提高收率,降低成本。方法以邻苯甲酰苯甲酸为起始原料,经三氯化磷酰化,N-甲基乙醇胺胺化,三氯化磷氯化,硼氢化钾还原,然后和氯化氢反应得盐酸奈福泮。结果收率提高了15%,原料成本每公斤降低了50元左右。结论改进后的工艺路线科学、合理,是一个较好的工艺合成路线。     

2-氨基-1,3-丙二醇的合成

目的制备2-氨基-1,3-丙二醇。方法以丙二酸二乙酯为原料,经亚硝基化、金属钠乙醇还原得到2-氨基-1,3-丙二醇(1)。结果与结论经1H NMR分析确证目标产物结构,总收率53.5%。该路线原料廉价易得,成本较低,反应条件温和,适用于工业生产。     

The role of monoamines in the actions of established and "novel" antidepressant agents: a critical review

Monoaminergic pathways are highly responsive to aversive stimuli and play a crucial role in the control of affect, cognition, endocrine secretion, chronobiotic rhythms, appetite, and motor function, all of which are profoundly disrupted in depressive states. Accordingly, a perturbation of monoaminergic transmission is implicated in the aetiology of depressive disorders, and all clinically available antidepressants increase corticolimbic availability of monoamines. However, their limited efficacy, delayed onset of action, and undesirable side effects underlie ongoing efforts to identify improved therapeutic agents. Sequencing the human genome has raised the hope not only of better symptomatic control of depression, but even of the prevention or cure of depressive states. In the pursuit of these goals, there is currently a tendency to focus on selective ligands of “novel” nonmonoaminergic targets. However, certain classes of novel agent (such as neurokinin₁ receptor antagonists) indirectly modulate the activity of monoaminergic networks. Others may act “downstream” of them, converging onto common cellular substrates controlling gene expression, synaptic plasticity, and neurogenesis. Further, by analogy to the broad-based actions of currently employed drugs, multitarget agents may be better adapted than selective agents to the management of depression—a complex disorder with hereditary, developmental, and environmental origins. It is, thus, important to continue the creative exploration of clinically validated and innovative monoaminergic strategies within a multitarget framework. In this light, drugs combining monoaminergic and nonmonoaminergic mechanisms of action may be of particular interest. The present article provides a critical overview of monoaminergic strategies for the treatment of depressive states, both established and under development, and discusses interactions of novel “nonmonoaminergic” antidepressants with monoaminergic mechanisms.     

麻醉对妇科腹腔镜患者肺内分流及血气影响

目的分析七氟醚、异氟醚与地氟醚复合异丙酚在对妇科腹腔镜手术患者肺内分流及血气的影响。方法选取我院2010年4月-2013年4月收治的192例行腹腔镜手术的妇科患者,按照患者意愿分为七氟醚、异氟醚和地氟醚组,各64例,分别接受七氟醚、异氟醚与地氟醚复合异丙酚麻醉,分析3组患者肺内血流和血气变化。结果随着插管和气腹的进行,3组患者Qs／Qt均见升高,而Pa02逐渐下降,放气后肺内分流逐渐恢复正常,地氟醚组患者肺内分流变化幅度最小（P〈0．05）;而3组患者血气水平变化相同,放气后血气水平逐渐恢复正常,地氟醚组患者血气水平变化幅度最小（P〈0．05）;3组患者气腹后均未见心律失常,肌松效果均满意,术后不适：七氟醚3例,2例咽部不适,1例肩部疼痛;异氟醚5例,4例咽部不适,1例肩部疼痛;地氟醚1例,为咽部不适。结论在今后妇科腹腔镜手术的麻醉诱导过程中,建议推广应用地氟醚复合麻醉,可得到优秀的可控性、镇痛深度,且能够保证肺内分流和血气稳定,减少并发症的发生。     

基于ICP-MS法对4种动物源性药材中16种无机元素的测定及量变规律研究

目的 测定地龙、土鳖虫、九香虫、蜂房4种动物源性药材中无机元素,并探索其元素量变规律。方法 采用微波消解法对样品进行前处理,电感耦合等离子体质谱（ICP-MS）法对地龙、土鳖虫、九香虫、蜂房中铍（Be）、钒（V）、钴（Co）、镍（Ni）、镓（Ga）、硒（Se）、铷（Rb）、锶（Sr）、银（Ag）、铯（Cs）、铀（U）、铜（Cu）、砷（As）、镉（Cd）、汞（Hg）和铅（Pb）16种无机元素进行测定,并采用元素指纹图谱直观分析、元素主成分分析、偏最小二乘判别分析、聚类分析对元素含量差异性进行统计分析。结果 16种无机元素的线性关系良好（R>0.996）,回收率为87.4～113.0%。4种动物药中检测了16种无机元素含量,并绘制无机元素指纹图谱,发现其谱图具有一定的特征性,4种动物药中As、Cd和Pb残留量较高,有害无机元素的量超标应引起关注。通过主成分分析、偏最小二乘法判别分析、聚类分析,发现不同样品元素之间含量变异均能呈现出明显特征,并以此可区分不同种类的动物药。结论 通过无机元素在4种动物药中的组成分布及其量的变化规律研究,为动物药的质量控制及安全性评价提供依据,同时为动物药重金属形态价态研究提供基础参考。     

黄芩素对人肝癌HepG2细胞生长的抑制作用

目的:研究黄芩素对人肝癌Hep G2细胞生长的抑制作用。方法:在培养Hep G2细胞的96孔板上加入药物,使黄芩素的终浓度分别为0、20、40、80、160μmol/L(即对照组与黄芩素1、2、3、4组)。采用MTT法检测细胞的存活情况,分光光度法检测含半胱氨酸的天冬氨酸蛋白水解酶(Caspase)-3、8、9的活性,并检测丙二醛(MDA)含量,超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性。结果:与对照组比较,培养24、48、72 h时,黄芩素2、3、4组各时间点的吸光度降低;培养24 h时,Caspase-3、8、9活性增强,MDA含量增加,SOD、GSH-Px活性减弱,差异均有统计学意义(P<0.01)。结论:黄芩素对Hep G2细胞生长具有抑制作用,其机制与增强Caspase-3、8、9活性,增加MDA含量,减弱SOD、GSH-Px活性有关。     

Psychotropic drugs and the ECG: focus on the QTc interval

The QT interval measuring depolarisation and repolarisation has, when lengthened, been implicated as a risk factor for the development of torsades de pointes and sudden death, particularly in patients predisposed to these complications due to cardiovascular impairment. Since some of the medications used in psychiatry have been implicated, an extensive review of available literature was made of the major classes, including antipsychotics, antidepressants, lithium, anticonvulsants and benzodiazepines. Further, where no publications were found on a particular medication, the pharmaceutical firms responsible for these items were contacted concerning possibly unpublished data. Results of the survey indicate that there may be difficulty in one of three situations: immediate (in the first minutes to hours after oral or parenteral administration), short-term use of 4 – 12 weeks or long-term use of ≥ 6 months. Based on this approach, the greatest concern is directed at the immediate application of haloperidol, droperidol, pimozide and trazodone, the short-term use of thioridazine, pimozide, sertindole, nortriptyline, clomipramine, doxepin and the long-term use of clozapine, olanzapine and carbamazepine. It is of interest that a reduction in QTc is reported with aripiprazole. Among the antidepressants, the tertiary tricyclic antidepressants (imipramine, amitriptyline and doxepin) appear to have a more general impact, while the secondary tricyclic antidepressants (nortriptyline, desipramine) may impact more on children and the elderly. Among other antidepressants, the only reports of torsades de pointes appeared to occur with mirtazapine. It was also of interest to find data showing no effect or reductions in QTc produced by sertraline, citalopram, paroxetine and bupropion in multiple studies. Effects of medications on other heart parameters are also briefly reviewed. In particular, the safety of sertraline in post-MI patients and of bupropion in heart disease patients is highlighted. Little information was available on other classes of medications used in psychiatric disorders. What is available concerning lithium, the anticonvulsants and the benzodiazepines indicates little effect on the QTc, although there may be effects on other cardiovascular parameters.     

The 17th International Conference on Antiviral Research

The focus of the 17th International Conference on Antiviral Research was the discovery and development of antiviral agents (chemistry, biology, animal models and clinical trial results) against a variety of human infectious agents including HIV, herpes viruses, hepatitis viruses, respiratory viruses and emerging/re-emerging pathogens. The meeting included the symposium ‘Clinical Update on Antiviral Drugs’, plenary sessions dedicated to each of the individual classes of infectious agents, a symposium on new developments surrounding emerging pathogens, and three special award lectures, which discussed the history of nucleotide antiviral agents, mechanisms of viral persistence and drug resistance, and the therapy of herpes virus infections. Within each infectious agent session the presentations included those describing the development of new and novel anti-infectives, including research based on the preclinical development of new molecules, and the results of animal modelling and clinical studies on advanced-stage antiviral agents. A summary of the meeting highlights, segregated by infectious agent, will be presented in this review.     

THE MICROBIAL BIOGENESIS OF AQUATIC BIOTOXINS

The biogenesis of small molecular nonprotein poisons has long been a mystery in the world of biotoxicology. The phylogenetic distribution, molecular structure, evidence of biogenesis, and possible mechanisms involving some of these poisons, such as saxitoxin, tetrodotoxin, ciguatoxin, palytoxin, maitotoxin, and brevitoxin, are briefly discussed.     

Acute pharmacodynamic tolerance to the subjective effects of cigarette smoking

A brief feeling state questionnaire was completed before and after each cigarette, over a day of smoking. Feelings of stress/anxiety demonstrated a pattern of repetitive vacilation over the day, with high stress before smoking, reduced stress after smoking, and stress levels increasing again between cigarettes. There was no evidence of acute pharmacodynamic tolerance, with cigarettes leading to altered feelings of anxiety/stress over the whole day of smoking. Self-rated feelings of arousal also demonstrated a pattern of vacilation over the day, with low arousal pre-smoking, increased arousal post-smoking, but arousal levels reducing again between cigarettes. The ANOVA drug × time interaction was significant, with the greatest arousal change following the first cigarette of the day. However, later cigarettes led to similar amounts of arousal change over the rest of day, thus questioning whether acute pharmacodynamic tolerance was occurring. Instead, the heightened arousal response to the first cigarette of the day may reflect the influence of two other factors. Firstly, overnight deprivation, with the first cigarette of the day leading to the greatest increase in plasma nicotine. Secondly, low early-morning arousal with its associated potential for increased arousal. Overall, therefore, there was little indication of acute pharmacodynamic tolerance to the subjective effects of nicotine. Cigarettes were associated with altered feelings of stress and arousal, over the whole day of smoking.     

兽用头孢噻呋在食品动物中的研究进展

头孢噻呋是第三代头孢菌素，在全球范围内被批准用于治疗猪、反刍动物(牛、绵羊和山羊)和马的呼吸道疾病，还被批准用于治疗牛的足腐病和子宫炎感染。许多国家还将头孢噻呋用于雏鸡的早期死亡和火鸡幼禽的感染。本文综述了头孢噻呋的结构活性、适应症、代谢、毒性以及在环境中的降解。同时，从食品动物残留、快速代谢和降解、环境中的非持久性等几个方面对头孢噻呋的安全性进行了总结。头孢菌素的环境脆性尚未被广泛研究，但可能是这类抗生素在动物中使用安全性方面的一个重要特征。