检索结果-南通市图书馆

A novel dual serotonin transporter and M-channel inhibitor D01 for antidepression and cognitive improvement

Acta Pharmaceutica Sinica B 2024年第3期14卷 1457-1466页

作者： Yaqin Wei Xiangqing Xu Qiang Guo Song Zhao Yinli Qiu Dongli Wang Wenwen Yu Yani Liu KeWei Wang School of Pharmacy Xuzhou Medical UniversityXuzhou 221004China Institute of Pharmaceutical Research Jiangsu Nhwa Pharmaceutical Co.Ltd.&Jiangsu Key Laboratory of Central Nervous System Drug Research and DevelopmentXuzhou 221116China Department of Pharmacology School of PharmacyQingdao University Medical CollegeQingdao 266073China Institute of Innovative Drug Qingdao UniversityQingdao 266021China Center for Brain Science and Brain-Inspired Intelligence Guangdong-Hong Kong-Macao Greater Bay AreaGuangzhou 510515China

Cognitive dysfunction is a core symptom common in psychiatric disorders including depression that is primarily managed by antidepressants lacking efficacy in improving cognition.In this study,we report a novel dual serotonin transporter and voltage-gated potassium Kv7/KCNQ/M-channel inhibitor D01(a 2-methyl-3-aryloxy-3-heteroarylpropylamines derivative)that exhibits both anti-depression effects and improvements in cognition.D01 inhibits serotonin transporters(K_(i)=30.1±6.9 nmol/L)and M channels(IC_(50)=10.1±2.4μmol/L).D01 also reduces the immobility duration in the mouse FST and TST assays in a dose-dependent manner without a stimulatory effect on locomotion.Intragastric administrations of D01(20 and 40 mg/kg)can significantly shorten the immobility time in a mouse model of chronic restraint stress(CRS)-induced depression-like behavior.Additionally,D01 dose-dependently improves the cognitive deficit induced by CRS in Morris water maze test and increases the exploration time with novel objects in normal or scopolamine-induced cognitive deficits in mice,but not fluoxetine.Furthermore,D01 reverses the long-term potentiation(LTP)inhibition induced by scopolamine.Taken together,our findings demonstrate that D01,a dual-target serotonin reuptake and M channel inhibitor,is highly effective in the treatment-resistant depression and cognitive deficits,thus holding potential for development as therapy of depression with cognitive deficits.

关键词： sert 5-HT Kv7/KCNQ/M current D01 Depression Cognition

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Nucleotide Contribution to the Functioning of sert, Na/K ATPase and GPCR Proteins

引用

Journal of Biosciences and Medicines 2024年第5期12卷 61-76页

作者： Wynford Robert Williams Faculty of Life Sciences & Education University of South Wales Cardiff UK

Purine nucleotides are crucial for the effective operation of cell membrane proteins maintaining the neurotransmitter responses of 5-HT. Major protein targets in the treatment of depression include sert, N/K ATPase and GPCR. Each protein target is responsive to a specific complement of drugs: antidepressants (sert), lithium and cardiogenic steroids (N/K ATPase), 5-HT receptor ligands (GPCR). Computational software is useful for comparing molecular similarity within ligand-ligand and ligand-nucleotide structures. Previous studies demonstrate that GPCR ligands of different pharmacologic classes display relative molecular similarity to nucleotide structures. The current study applies this methodology to compound structures modulating sert and N/K ATPase receptors. Minimum energy conformers of sert antagonists demonstrate relative molecular similarity to the structural template of GTP nucleotide. GTP template fits of 5-HT and psilocin are similar, whereas a sert-like fit is one of several for the ketamine structure. Endogenous and pharmaceutical modulators of Na/K ATPase relate to adenine nucleotide. The fits of cardiogenic steroids to a cGMP template demonstrate similarities and differences between compounds. Relative molecular similarity within the structures of hormones, drugs and nucleotides has implications for neurotransmitter transport and cell signal transduction processes.

关键词： sert SSRI GPCR Sodium/Potassium ATPase Nucleotides Depression

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Fast-onset antidepressant targeting the nNOS-sert interaction in the DRN

引用

Chinese Journal of Natural Medicines 2023年第1期21卷 1-2页

作者： GUAN Xin PANG Tao State Key Laboratory of Natural Medicines New Drug Screening CenterChina Pharmaceutical UniversityNanjing 210009China

Major depressive disorder is one of the most deleterious mental disorders with a high suicide rate,incidence and recurrence rate,which is manifested as continuous depression,retardation of thinking as well as loss of ... 详细信息

关键词： Depression nNOS sert Antidepressant Fast-onset

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

盐酸氟西汀对高原脑水肿大鼠脑组织的保护作用

引用

中国药理学通报 2022年第9期38卷 1382-1388页

作者：邹蓓蕾潘菁吴庆丰张朋朋石志群田贻婷李文斌马慧萍联勤保障部队第九四〇医院药剂科甘肃兰州730050 联勤保障部队第九四〇医院卫勤部甘肃兰州730050 中国科学院近代物理研究所甘肃兰州730000

目的研究盐酸氟西汀对模拟高原脑水肿大鼠脑组织的保护作用及其作用机制。方法通过小鼠常压密闭缺氧耐受力实验确定盐酸氟西汀最佳给药剂量及给药时间;采用大型低压氧舱进行高原脑水肿大鼠造模;HE染色观察大鼠脑组织病理学结构变化;酶... 详细信息

目的研究盐酸氟西汀对模拟高原脑水肿大鼠脑组织的保护作用及其作用机制。方法通过小鼠常压密闭缺氧耐受力实验确定盐酸氟西汀最佳给药剂量及给药时间;采用大型低压氧舱进行高原脑水肿大鼠造模;HE染色观察大鼠脑组织病理学结构变化;酶标仪法检测丙二醛(MDA)水平和超氧化物歧化酶(SOD)活性;Western blot法检测缺氧相关蛋白HIF-1α、VEGF、MMP-9以及AQP4、sert的表达。结果与缺氧模型组相比,给予盐酸氟西汀干预后:小鼠存活时间延长,盐酸氟西汀中剂量组(14 mg·kg^(-1))效果最佳,延长率为17.78%;脑组织病理损伤有所改善,脑含水量减少,血脑屏障渗透性减小;大鼠脑组织内MDA含量减少,SOD活性增强。Western blot结果表明,HIF-1α、VEGF、MMP-9、AQP4、sert蛋白均明显下调。结论盐酸氟西汀对高原脑水肿大鼠具有保护作用,其机制可能与改善氧化应激、激活HIF-1α/VEGF/MMP-9信号通路并且影响sert蛋白表达有关,sert可能为治疗高原脑水肿的潜在靶点。

关键词：氟西汀高原脑水肿 sert 氧化应激炎症血管生成

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

nNOS-mediated protein-protein interactions:promising targets for treating neurological and neuropsychiatric disorders

引用

The Journal of Biomedical Research 2021年第1期35卷 1-10页

作者： Yuanyuan Gu Dongya Zhu Department of Pharmacology School of PharmacyNanjing Medical UniversityNanjingJiangsu 211166China Institution of Stem Cell and Neuroregeneration School of PharmacyNanjing Medical UniversityNanjingJiangsu 211166China

Neurological and neuropsychiatric disorders are one of the leading causes of disability worldwide and affect the health of billions of people.Nitric oxide(NO),a free gas with multitudinous bioactivities,is mainly produced from the oxidation of L-arginine by neuronal nitric oxide synthase(nNOS)in the brain.Inhibiting nNOS benefits a variety of neurological and neuropsychiatric disorders,including stroke,depression and anxiety disorders,posttraumatic stress disorder,Parkinson’s disease,Alzheimer’s disease,chronic pain,and drug addiction.Due to critical roles of nNOS in learning and memory and synaptic plasticity,direct inhibition of nNOS may cause severe side effects.Importantly,interactions of several proteins,including post-synaptic density 95(PSD-95),carboxyterminal PDZ ligand of nNOS(CAPON)and serotonin transporter(sert),with the PSD/Disc-large/ZO-1 homologous(PDZ)domain of nNOS have been demonstrated to influence the subcellular distribution and activity of the enzyme in the brain.Therefore,it will be a preferable means to interfere with nNOS-mediated proteinprotein interactions(PPIs),which do not lead to undesirable effects.Herein,we summarize the current literatures on nNOS-mediated PPIs involved in neurological and neuropsychiatric disorders,and the discovery of drugs targeting the PPIs,which is expected to provide potential targets for developing novel drugs and new strategy for the treatment of neurological and neuropsychiatric disorders.

关键词： nNOS PSD-95 CAPON sert protein-protein interaction neurological and neuropsychiatric disorder

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Biological evaluation on ^(125)I-ADAM as serotonin transporter ligand

引用

Nuclear Science and Techniques 2007年第4期18卷 218-222页

作者： LEI Bei ZHU Junqing LU Chunxiong JIANG Quanfu ZOU Meifeng WANG Songpei LI Xiaomin WU Chunying The Key Laboratory of Nuclear Medicine Ministry of Health Jiangsu Institute of Nuclear Medicine Wuxi 214063 China Huashan Hospital Fudan University Shanghai 200040 China

ADAM (2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine) is suggested as a promising serotonin transporter (sert) imaging agent for central nervous system. In this paper, biodistribution studies in rats showed that the initial uptake of 131I-ADAM in the brain was high (1.087%ID at 2 min post-injection), and consistently displayed the highest binding (between 60~240 min post-injection) in hypothalamus, a region known with the highest density of sert. The specific binding((T/CB)-1) of 131I-ADAM in hypothalamus were 2.94, 3.03 and 3.09 at 60, 120 and 240 min post-injection, respectively. The (T/CB)-1 was significantly blocked by pretreatment with paroxetine, which is known as a serotonin site reuptake inhibitor, while another nonselective competing drug (5HT2A antagonist) Ketanserin, showed no block effect. The rat brain autoradiography and analysis showed that there was a high 131I-ADAM uptake in hypothalamus, the ratio of hypothalamus/cerebellum was significantly reduced from 7.94±0.39 to 1.30±0.56 by pretreatment with paroxetine at 60 min post-injection. Blood clearance kinetics was performed in rats, and the initial half-life of 13.79 min and late half-life of 357.14 min were obtained. The kinetic equation is: C=3.6147e-0.0725t + 1.0413e-0.0028t. The thyroid uptake was 0.009% ID and 1.421% ID at 2 min and 120 min post-injection, respectively, suggesting that in vivo deiodination may be the major route of metabolism. Toxicity trial showed that the dose per kilogram administered to mice was 1000 times greater than that to humans, assuming a weight of 50kg. These data suggest that 131I-ADAM may be useful for SPECT imaging of sert binding sites in the brain.

关键词：抑郁症 sert ADAM 放射诊断复合胺生物分布

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

便塞通合剂对慢传输型便秘大鼠SCFAs-sert-5-HT含量影响的实验研究

便塞通合剂对慢传输型便秘大鼠SCFAs-SERT-5-HT含量影响的实验研究

引用

作者：张智彬川北医学院

学位级别：硕士

目的:观察便塞通合剂(biansetong mixture,BST)对慢传输型便秘(slow transit constipation,STC)模型大鼠的干预作用,通过观测大鼠肠道短链脂肪酸(short chain fatty acids,SCFAs)、结肠sert和血清5-羟色胺(5-hydroxytryptamine,5-HT)在治疗中的变化规律和相关性,从而探讨BST治疗STC的作用机制,为STC的规范化治疗和临床用药提供依据。方法:32只SPF级雄性大鼠随机平均分为4组(A组,空白组;B组,模型组;C组,双歧杆菌三联活菌组;D组,便塞通合剂组)。A组不造模,予以蒸馏水灌胃;其余3组予以盐酸洛哌丁胺混悬液灌胃30天复制慢传输型便秘大鼠模型。模型稳定后,A组和B组不干预,予以蒸馏水灌胃,C组予以双歧杆菌三联活菌混悬液干预,D组予以便塞通合剂混悬液干预。干预结束后,通过对比各组大鼠的一般情况、8h粪便颗粒、首颗黑便时间、粪便含水量、小肠碳末推进率和结肠滞留粪便颗粒等,观察和比较两种药物治疗STC的效果。采用ELISA测定大鼠血清5-HT含量,实时荧光定量PCR和免疫组化测定结肠sert蛋白和mRNA的表达情况,气相色谱法测定结肠SCFAs含量。结果:①经过30天的造模,B组、C组和D组大鼠与A组相比,首颗黑便时间延长(P0.05),但粪便含水量明显增加(Psert蛋白和mRNA的表达水平升高(Psert的表达水平明显降低(Psert蛋白表达量较C组降低明显(Psert蛋白表达量方面优于双歧杆菌三联活菌。2、BST干预后结肠短链脂肪酸含量明显增高,sertmRNA和蛋白表达量明显降低,及血清5-HT含量明显增高,STC改善明显,但短链脂肪酸、sert以及5-HT在BST治疗STC中的作用机制尚需更进一步研究。

关键词：便塞通合剂慢传输型便秘短链脂肪酸 sert 5-HT

来源：

同方学位论文库评论

在线全文

同方学位论文库

学校读者我要写书评

暂无评论

Reduction of serotonergic gene expression in the raphe nuclei of the midbrain under positive fighting experience in male mice

引用

Advances in Bioscience and Biotechnology 2013年第10期4卷 36-44页

作者： Dmitry A. Smagin Ul’yana A. Boyarskikh Natalya P. Bondar Maxim L. Filipenko Natalia N. Kudryavtseva Institute of Chemical Biology and Basic Medicine Siberian Department of Russian Academy of Sciences Novosibirsk Russia Institute of Cytology and Genetics Siberian Department of Russian Academy of Sciences Novosibirsk Russia

The concept of a major inhibitory role of serotonin in aggressive behavior is widely accepted by investigators. There was ample evidence that a pharmacologically-induced increase in the serotonin activity attenuates agonistic behavior in animals, and that the manipulations inhibiting the brain serotonergic system can elicit aggressiveness in male mice and rats. Repeated experience of aggression in daily agonistic interactions has been shown to reduce serotonin activity in brain of victorious male mice. The study aimed to analyze expression of the serotonergic genes -Tph2, sert, Maoa and Htr1a, as well as the Bdnf and Creb genes in the midbrain raphe nuclei of male mice with positive fighting experience in daily encounters and male mice with the same track record of aggression followed by two-week no-fight period. It has been shown that mRNA levels of the serotonergic and Creb genes are reduced in the winners in comparison with male mice without consecutive positive fighting experience of aggression. After the fighting deprivation the Tph2, sert, Bdnf and Creb genes recover their expression while mRNA levels of the Maoa and Htr1a genes proceed at a significantly higher level as compared with the respective controls. Downregulation of serotonergic genes is indicative of the inhibition of serotonergic activity under repeated experience of aggression. Nevertheless recovering of Tph2 and sert gene expression and overexpression of the Maoa and Htr1a genes after no-fight period suggest that changes in brain serotonergic activity are not main cause of the behavioral pathology developing in male mice in this experimental context.

关键词： Tph2 sert MaoA Bdnf Creb mRNA Repeated Aggression Fighting Deprivation

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

喷他佐辛的药代动力学及药效学研究

引用

广东医学 2010年第10期31卷 1216-1218页

作者：赵国栋孙来宝黄文起广东省人民医院广东省医学科学院麻醉科广州510080 中山大学附属第一医院麻醉科广州510080

喷他佐辛(pentazocine)是人工合成的阿片类药苯并吗啡烷的衍生物,是阿片受体的激动-拮抗剂.阿片类药(opioid)源自于鸦片(opium),关于鸦片的确切记载最早可追溯至公元前3世纪《Theophrastus》的记录~[1].鸦片包含有20多种植物碱,至1806年... 详细信息

喷他佐辛(pentazocine)是人工合成的阿片类药苯并吗啡烷的衍生物,是阿片受体的激动-拮抗剂.阿片类药(opioid)源自于鸦片(opium),关于鸦片的确切记载最早可追溯至公元前3世纪《Theophrastus》的记录~[1].鸦片包含有20多种植物碱,至1806年, sertürner报道在鸦片里分离出一种的纯化物,并将其命名为"Morpheus"———意为:希腊的梦神.随后在医学领域里,鸦片的纯化物开始被广泛使用.然而,人们在发挥阿片类药有利一面的同时也逐渐认识到其背后隐藏着不利的一面,如毒性作用以及成瘾性等,于是人们开始寻找更新,不良反应更少的阿片类药.与此同时也合成了阿片类药的拮抗剂以及阿片受体的激动-拮抗剂,增加了人们对阿片类药的选择,同时也拓宽了阿片类药作用机制的研究领域.随新型片类药的研发应用,新的用药方式也随之而来,如患者自控镇痛(patient-controlled analgesia, PCA)技术,芬太尼透皮贴的应用.本文就喷他佐辛与阿片类药物的药代动力学及药效学进行比较,为临床应用提供依据

关键词：喷他佐辛药代动力学药效学阿片类药人工合成阿片受体 sert 医学领域

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

功能性便秘、功能性腹泻和肠易激综合征病人sert基因多态性分析

引用

基础医学与临床 2003年第Z1期23卷 82-83页

作者：王玉明王邦茂张维铭张庆瑜姜葵张洁天津医科大学总医院消化内科天津300052 天津医科大学实验中心

目的旨在研究sert基因多态性在FC、FDi、C-IBS、D-IBS和A-IBS中的分布特征,探寻其在这些功能性肠病(Functional bowel disorders,FBDs)发病机制中的意义.方法1.病人及对照组:依照罗马Ⅱ标准选取FC 31例、FDi 30例、C-IBS 30例、D-IBS 3... 详细信息

目的旨在研究sert基因多态性在FC、FDi、C-IBS、D-IBS和A-IBS中的分布特征,探寻其在这些功能性肠病(Functional bowel disorders,FBDs)发病机制中的意义.方法1.病人及对照组:依照罗马Ⅱ标准选取FC 31例、FDi 30例、C-IBS 30例、D-IBS 32例、A-IBS19例;48例健康对照组.

关键词： IBS 基因型 sert 遗传型遗传多态性基因多态性 FC 病人

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

欢迎您,

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案：

请选择收藏分类：

通借通还

欢迎您,

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：