抗抑郁新药马来酸氟伏沙明的合成

目的研究抗抑郁新药马来酸氟伏沙明的合成.方法以苯甲酸乙酯为起始原料,经取代、氨解、水解、成盐4步反应合成马来酸氟伏沙明(8).结果与结论以苯甲酸乙酯为起始原料,合成了马来酸氟伏沙明,总收率为51%.改进了中间体2-溴乙基邻苯二甲酰亚胺(4)的合成工艺.     

马来酸氟伏沙明的合成

1-氯-4-甲氧基丁烷与对三氟甲基苄腈经格氏反应得到5-甲氧基-1-(4-三氟甲基苯基)戊酮,与盐酸羟胺成肟后经与2-氯乙胺盐酸盐缩合及成盐反应制得抗抑郁药马来酸氟伏沙明,总收率40%(以对三氟甲基苄腈计).     

氟伏沙明抑制体内氯氮平代谢的药代动力学研究

通过检测氯氮平和去甲氯氮平血清浓度，探讨细胞色素Ｐ４５０１Ａ２酶（ＣＹＰ１Ａ２）抑制剂氟伏沙明对体内氯氮平代谢及其去甲基代谢产物生成的影响。９例健康男性志愿者，自身前后对照设计，停药间隔４周，口服单剂氯氮平１０ｍｇ；对照组单服氯氮平，实验组是在氟伏沙明连续９ｄ服用过程中的第４ｄ合用单剂氯氮平，合用氟伏沙明后，导致氯氮平的清除相对点平均浓度增高。去甲氯氮平的早期时点平均浓度降低而后期时点平均浓度增高     

氟伏沙明与马普替林的抗抑郁与抗焦虑作用的研究

目的：探讨氟伏沙明治疗伴有焦虑症状的抑郁症的疗效与安全性。方法：将69例难治性抑郁症同时伴有焦虑症状的患者分为氟伏沙明组35例,马普替林组34例。观察8周,于治疗前和治疗后1、2、4及8周末采用汉密尔顿抑郁量表（HAMD-17）及汉密顿焦虑量表（HAMA）评定疗效。用副反应量表（TFSS）评定不良反应。结果：氟伏沙明组显效率为78%,马普替林组显效率为75%。氟伏沙明组不良反应相对较少。结论：氟伏沙明治疗伴发焦虑症状的抑郁症疗效较好,且起效快,不良反应少。     

氟伏沙明治疗儿童少年强迫症40例

目的观察氟伏沙明治疗儿童和少年强迫症的疗效及不良反应。方法40例强迫症患者给予氟伏沙明25～200 mg·d^-1，＜10岁儿童患者，起始药量25 mg，PO，qn，≥10岁患者，起始药量50 mg，PO，qn。在治疗前和治疗第2，6周末用YALE BROWN（Y-B）强迫量表、临床总体印象量表及不良反应量表对疗效和不良反应进行评定。结果治疗2周后Y-B量表总分、强迫行为分降低，与治疗前比较差异有极显著性（P＜0. 01）。治疗6周后 Y-B量表总分、强迫思维分、强迫行为分与治疗前比较差异均有极显著性（均P＜0.01）。强迫行为分减分率高于强迫思维减分率（P＜0.01）。早期有思睡、恶心，治疗第6周后未发现明显不良反应。结论氟伏沙明是一种有效且安全性较好的治疗儿童和少年强迫症的药物。     

氟伏沙明治疗强迫症23例

目的 探索氟伏沙明与氯米帕明治疗强迫症的疗效和不良反应. 方法 将46例强迫症患者随机分为治疗组和对照组各23例, 治疗组给予氟伏沙明, 对照组给予氯米帕明治疗, 疗程8周. 治疗组平均剂量（257.61±47.93） mg&#8226;d-1, 对照组平均剂量（209.78±34.33） mg&#8226;d^-1. 于治疗前及治疗第2, 4, 6, 8周末采用Yale Brown强迫量表（YBOCS）评价其疗效, 治疗中采用不良反应量表（TESS）评价其不良反应. 结果 两组治疗前YBOCS评分差异无显著性（P>0.05）; 从治疗第2周末开始两组YBOCS评分均较前有显著下降（P<0.01）, 同期组间比较差异无显著性（P>0.05）; 治疗8周末治疗组有效率65.22%, 对照组有效率69.56%, 两组差异无显著性（P>0.05）; 治疗组不良反应较对照组少且轻. 结论 氟伏沙明是一种安全有效的短期治疗强迫症的药物.     

氟伏沙明联合利培酮治疗精神分裂症的疗效研究

目的:探讨氟伏沙明联合利培酮对精神分裂症患者临床疗效、认知障碍、阳性和阴性症状及生活质量的影响.方法:选取2018年9月至2020年12月在西安交通大学医学院第一附属医院精神科进行治疗的精神分裂症患者304例,根据随机数字表法分为氟伏沙明组(n=152)与对照组(n=152).对照组患者采用利培酮片口服治疗,氟伏沙明组...     

齐拉西酮联合氟伏沙明治疗强迫症的对照研究

目的：探讨齐拉西酮联合氟伏沙明治疗强迫症的临床疗效方法：将符合人组条件的60例强迫症患者随机分为治疗组和对照组各30例,均予氟伏沙明口服,起始剂量25mg／d,剂量范围100—250mg／d;治疗组在此基础上加用齐拉西酮,起始剂量40mg／d,剂量范围60—120mg／d,两组均治疗8周。于治疗前及治疗后2、4、8周末采用强迫症量表（Y—BOCS）评定疗效,同时予以副反应量表（TESS）评定不良反应。结果：在治疗2、4、8周末,两组Y—BOCS的评分均降低,但治疗组较对照组均下降明显（P〈0．05）;两组副反应量表（TESS）评分差异无统计学意义。结论：齐拉西酮联合氟伏沙明治疗强迫症临床疗效优于单用氟伏沙明,安全性两组相当。     

氟伏沙明合并认知行为疗法治疗强迫症的研究

目的评价氟伏沙明合并认知行为疗法对强迫症的治疗效果。方法将符合中国精神障碍分类与诊断标准的55例强迫症患者随机分为治疗组和对照组,治疗组给予氟伏沙明合并认知行为治疗,对照组给予氟伏沙明治疗。应用临床疗效标准及耶鲁布朗强迫量表(Y-BOCS)定期评定,观察6个月。结果在治疗1、2、4个月和6个月末,治疗组疗效显著优于对照组,尤其对强迫行为疗效更好,具有极显著统计学意义(P<0.01)。结论氟伏沙明合并认知行为疗法联合治疗强迫症效果优于单用氟伏沙明治疗。     

氟伏沙明联合利培酮治疗强迫症29例

目的探讨氟伏沙明联合利培酮治疗强迫症的临床疗效。方法将57例强迫症患者随机分为两组,治疗组29例,口服氟伏沙明联合利培酮治疗;对照组28例,单用利培酮治疗。氟伏沙明起始25 mg&#8226;d-1,剂量范围100～250 mg&#8226;d-1;利培酮起始0.5 mg&#8226;d-1,剂量范围1～3 mg&#8226;d-1。均治疗8周。于治疗前及治疗2,4,8周末采用Y BOCS评定临床疗效。结果在治疗2,4,8周末,治疗组Y BOCS评分较对照组均显著下降(P＜0.05)。治疗2,4,8 周末,治疗组临床显效分别为0,2,15例,对照组分别为0,0,7例。结论治疗8周后,氟伏沙明联合利培酮治疗强迫症疗效优于单用氟伏沙明。     

越鞠丸及各单味药醇提物对小鼠的抗抑郁作用研究

目的:探讨越鞠丸全方及各单味药(香附、川芎、栀子、苍术、神曲)醇提物的抗抑郁活性。方法:采用小鼠悬尾和强迫小鼠游泳实验2种行为绝望法复制小鼠抑郁模型,对越鞠丸全方及各单味药分别进行抗抑郁活性研究。结果:除神曲外,越鞠丸全方及各单味药醇提物均能不同程度地缩短小鼠悬尾不动时间和小鼠强迫游泳不动时间,具有抗抑郁样活性;越鞠丸全方醇提物、苍术和川芎可显著缩短小鼠悬尾不动时间和游泳不动时间。结论:越鞠丸全方及香附、苍术、川芎、栀子醇提物均有不同程度的抗抑郁活性,其抗抑郁活性部位/成分可能主要存在于苍术、川芎2味药材之中。     

绿萼梅提取物对小鼠的抗抑郁作用

目的：观察绿萼梅提取物对小鼠的抗抑郁作用。方法采用悬尾实验（ TFT）、强迫游泳（ FST）等体内药效评价方法观察绿萼梅醇提取物和水提取物对抑郁模型小鼠的治疗作用。结果绿萼梅醇提物能明显缩短小鼠悬尾和强迫游泳不动时间（ P＜0．05）,且对自主活动无影响（ P＞0．05）;而水提物对小鼠悬尾和强迫游泳不动时间无显著影响（ P＞0．05）。结论绿萼梅乙醇提取物具有抗小鼠抑郁作用。     

Influence of naloxone on antidepressant drug effects in the forced swimming test in mice

The influence of naloxone on the effects of several antidepressant drugs, atropine and caffeine was studied in the forced swimming test in mice. Naloxone itself has no effect in this test, but significantly reduces that of two tricyclic antidepressants, clomipramine (20 and 30 mg/kg) and desipramine (20 and 30 mg/kg). Except for clorgyline at the high dose of 60 mg/kg, no significant reduction of activity by naloxone was observed with other antidepressants (pargyline, nomifensine and mianserin), nor with caffeine and atropine. These results are discussed in terms of the pharmacological characteristics of each drug and of the test used. No straightforward interaction between cholinergic or monoaminergic and endorphinic systems is evident. Possible action at opiate receptor sites is discussed.     

Synthesis and Evaluation on Anticonvulsant and Antidepressant Activities of 5-Alkoxy-tetrazolo[1,5-a]quinazolines

Several 5-alkoxy-tetrazolo[1,5-a]quinazoline derivatives have been synthesized by reacting 2,4-dichloroquinazoline with various phenols or aliphatic alcohol and then with sodium azide. The structures of these compounds have been confirmed by IR, MS, ¹H-NMR, and elementary analysis. Anticonvulsant activities were evaluated using the maximal electroshock (MES) test. Most of the synthesized compounds displayed weak anticonvulsant activity at a dose of 300 mg/kg. Antidepressant activities were investigated by forced swimming test. Two compounds, namely 5-(hexyloxy)tetrazolo[1,5-a]quinazoline and 5-(4-methoxyphenoxy)tetrazolo[1,5-a]quinazoline, showed significant antidepressant activity, which decreased the immobility time by 62.2 and 51.7% at 100 mg/kg dose level.     

罗布麻叶抗抑郁活性部位的筛选

目的:筛选罗布麻叶的抗抑郁活性部位,并探讨抗抑郁活性与总黄酮含量的关系。方法:用小鼠强迫游泳实验评价抗抑郁作用;用荧光分光光度法测定单胺类神经递质;用紫外分光光度法测定总黄酮的含量。结果:罗布麻叶乙醇提物对小鼠的不动时间没有显著的影响,而其他4个部位均可不同程度的降低小鼠的不动时间,其中正丁醇部位和水相部位的作用最强。罗布麻叶乙醇提取物显著降低了5-HT在纹状体中的浓度,而石油醚、乙酸乙酯、正丁醇和水相部位对NA、DA、5-HT在海马,纹状体中的浓度有不同程度的影响。结论:罗布麻叶醇提物没有抗抑郁活性,但其他四个部位具有抗抑郁活性,其活性成分主要分布在正丁醇和水溶性部位,且抗抑郁活性与总黄酮含量没有线性关系。     

Antidepressant Effect of Baicalin Extracted from the Root of Scutellaria baicalensis. in Mice and Rats

Abstract

The flavonoid baicalin, isolated from the dried root of Scutellaria baicalensis. G. (Labiatae), is widely used in traditional Chinese herbal medicine. In the present study, baicalin, at doses of 20, 40, and 80 mg/kg (p.o.), reduced immobility time in tail suspension test (TST) and the forced swimming test (FST) in mice. Baicalin also decreased immobility time at 12.5, 25, and 50 mg/kg (p.o.) in FST in rats. Furthermore, baicalin (25 mg/kg), as well as fluoxetine (FLU; 20 mg/kg), showed a significant recovery in sucrose intake compared with the vehicle-treated stressed animals for 5 weeks treatment in a chronic mild stress (CMS) model in rats. The effect of baicalin at the dose of 25 mg was as potent as that of reference antidepressant FLU (20 mg/kg) in the CMS model. With the monoamine oxidase (MAO A and B) assay, oral administration of baicalin at the doses of 12.5, 25, and 50 mg/kg significantly inhibited MAO A activity in a dose-dependent manner in rats. However, only baicalin at the doses of 25 and 50 mg/kg markedly inhibited MAO B activity. Neither baicalin nor FLU, at the doses tested, produced a significant effect on locomotor activity in mice. These results suggest that baicalin had a specific antidepressant-like effect in vivo.. The antidepressant activity of baicalin may be mediated in part through MAO A and B inhibition in rat brain.     

Simultaneous analyses of the neurochemical and behavioral effects of the norepinephrine reuptake inhibitor reboxetine in a rat model of antidepressant action

Abstract Rationale. The forced swimming test (FST) is a rodent behavioral assay widely used to predict clinical efficacy of putative antidepressants. Few studies have examined the effects of the FST on neurotransmitter levels and how antidepressant drug treatment may alter neurotransmitter levels and behavior simultaneously during the performance of a stressful task. Objectives. The present study examined the role of norepinephrine in mediating active behaviors in the FST after treatment with reboxetine, a selective norepinephrine reuptake inhibitor. Methods. High-pressure liquid chromatography was used to analyze microdialysis samples collected from awake, freely moving rats before, during and after exposure to the FST. Reboxetine (10 mg/kg) was given three times over a 24-h period prior to the test swim. Behavioral responses, including immobility, swimming and climbing, were counted during the 5-min test on day 1 and day 2. Results. The first exposure to swim stress elicited a 65% increase in extracellular norepinephrine (NE). A second exposure on day 2 elicited a 52% increase of NE and a behavioral profile characterized by increased immobility and a reduction of active behaviors. A subchronic course (three injections over 24 h) of treatment with reboxetine between the two swim exposures resulted in antidepressant-like activity, i.e., decreased immobility and increased climbing behavior on day 2. A significantly greater increase in extracellular NE (112%) was observed in the group of animals that received reboxetine injections. Conclusions. Treatment with reboxetine in a schedule commonly used in the FST resulted in a potentiated noradrenergic response to the swim challenge concomitant with behavioral alterations consistent with antidepressant-like activity. Electronic Publication     

槟榔壳总酚类提取物抗抑郁作用研究

目的:探讨槟榔壳总酚类提取物对抑郁模型小鼠的抗抑郁作用。方法:采用小鼠悬尾、强迫游泳等抑郁模型,以小鼠行为绝望的不动时间作为指标,考察槟榔壳总酚类抗抑郁活性。结果:槟榔壳总酚类320,160 mg.kg-1剂量组均能显著减少小鼠悬尾和强迫游泳的不动时间。结论:槟榔壳总酚类可以改善小鼠的绝望行为,具有明显的抗抑郁作用。     

人参总皂苷对小鼠的抗抑郁作用

目的：初步探讨人参总皂苷对小鼠的抗抑郁作用。方法：选取健康雄性昆明种小鼠,随机分为5组,空白对照组、阳性药组、人参总皂苷125、250、500 mg.kg^-1剂量组。通过小鼠自主活动实验、小鼠强迫游泳实验和小鼠悬尾实验,观察人参总皂苷对小鼠抗抑郁作用的影响。结果：各给药组小鼠自主活动行为与空白对照组比较均无明显差异;人参总皂苷125、250、500 mg.kg-1均可以显著缩短小鼠强迫游泳及小鼠悬尾不动时间。结论：实验结果表明人参总皂苷在小鼠＂行为绝望＂模型中有一定的抗抑郁作用。