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Pharmacokinetics of Caffeine following a Single Administration of Coffee Enema versus Oral Coffee Consumption in Healthy Male Subjects. 在健康男性受试者中,单次给药咖啡灌肠与口服咖啡后咖啡因的药代动力学
Pub Date : 2013-01-01 Epub Date: 2013-03-04 DOI: 10.1155/2013/147238
Supanimit Teekachunhatean, Nisanuch Tosri, Noppamas Rojanasthien, Somdet Srichairatanakool, Chaichan Sangdee

The objective of this study was to determine the pharmacokinetics of caffeine after single administration of a coffee enema versus coffee consumed orally in healthy male subjects. The study design was an open-label, randomized two-phase crossover study. Eleven healthy subjects were randomly assigned either to receive 500 mL of coffee enema for 10 minutes or to consume 180 mL of ready-to-drink coffee beverage. After a washout period of at least 10 days, all the subjects were switched to receive the alternate coffee procedure. Blood samples were collected immediately before and at specific time points until 12 hours after coffee administration in each phase. The mean caffeine content in both the coffee solution prepared for the coffee enema and the ready-to-drink coffee beverage was not statistically different. The C max and AUC of caffeine obtained from the coffee enema were about 3.5 times significantly less than those of the coffee consumed orally, despite having slightly but statistically faster T max. The t 1/2 of caffeine obtained following both coffee procedures did not statistically differ. In summary, the relative bioavailability of caffeine obtained from the coffee enema was about 3.5 times significantly less than those of the coffee consumed orally.

本研究的目的是确定在健康男性受试者中,单次给予咖啡灌肠与口服咖啡后咖啡因的药代动力学。研究设计为开放标签、随机两期交叉研究。11名健康受试者被随机分配,要么接受500毫升咖啡灌肠,持续10分钟,要么饮用180毫升即饮咖啡饮料。在至少10天的洗脱期后,所有受试者都被切换到接受替代咖啡程序。在每个阶段的咖啡给药前和特定时间点采集血液样本,直到12小时后。在为咖啡灌肠准备的咖啡溶液和即饮咖啡饮料中,咖啡因的平均含量没有统计学上的差异。从咖啡灌肠中获得的咖啡因的最大C值和AUC值是口服咖啡的3.5倍,尽管最大T值略快,但从统计学上讲。两种方法所获得的咖啡因含量没有统计学差异。总之,从咖啡灌肠中获得的咖啡因的相对生物利用度大约是口服咖啡的3.5倍。
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引用次数: 54
Scientific challenges and implementation barriers to translation of pharmacogenomics in clinical practice. 药物基因组学翻译在临床实践中的科学挑战和实施障碍。
Pub Date : 2013-01-01 Epub Date: 2013-02-28 DOI: 10.1155/2013/641089
Y W Francis Lam

The mapping of the human genome and subsequent advancements in genetic technology had provided clinicians and scientists an understanding of the genetic basis of altered drug pharmacokinetics and pharmacodynamics, as well as some examples of applying genomic data in clinical practice. This has raised the public expectation that predicting patients' responses to drug therapy is now possible in every therapeutic area, and personalized drug therapy would come sooner than later. However, debate continues among most stakeholders involved in drug development and clinical decision-making on whether pharmacogenomic biomarkers should be used in patient assessment, as well as when and in whom to use the biomarker-based diagnostic tests. Currently, most would agree that achieving the goal of personalized therapy remains years, if not decades, away. Realistic application of genomic findings and technologies in clinical practice and drug development require addressing multiple logistics and challenges that go beyond discovery of gene variants and/or completion of prospective controlled clinical trials. The goal of personalized medicine can only be achieved when all stakeholders in the field work together, with willingness to accept occasional paradigm change in their current approach.

人类基因组的绘制和随后遗传技术的进步使临床医生和科学家了解了改变药物药代动力学和药效学的遗传基础,以及在临床实践中应用基因组数据的一些例子。这提高了公众的期望,即预测患者对药物治疗的反应现在在每个治疗领域都是可能的,个性化药物治疗迟早会到来。然而,在参与药物开发和临床决策的大多数利益相关者中,关于药物基因组学生物标志物是否应用于患者评估以及何时和在谁身上使用基于生物标志物的诊断测试的争论仍在继续。目前,大多数人都同意,实现个性化治疗的目标即使不是几十年,也需要几年的时间。基因组学发现和技术在临床实践和药物开发中的实际应用需要解决多种物流和挑战,而不仅仅是发现基因变异和/或完成前瞻性对照临床试验。个性化医疗的目标只有在该领域的所有利益相关者共同努力,并愿意接受当前方法中偶尔的范式改变时才能实现。
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引用次数: 52
Inhibitory Effect of Aqueous Extract of Stem Bark of Cissus populnea on Ferrous Sulphate- and Sodium Nitroprusside-Induced Oxidative Stress in Rat's Testes In Vitro. 山竹茎皮水提物对硫酸亚铁和硝普钠诱导大鼠睾丸氧化应激的抑制作用。
Pub Date : 2013-01-01 Epub Date: 2013-01-21 DOI: 10.1155/2013/130989
Seun F Akomolafe, Ganiyu Oboh, Afolabi A Akindahunsi, Ayodele J Akinyemi, Oluwatosin G Tade

Cissus populnea are plants associated with a myriad of medicinal uses in different parts of the world and are good sources of carotenoids, triterpenoids, and ascorbic acid. The antioxidant properties and inhibitory effect of water extractible phytochemicals from stem bark of C. populnea on FeSO(4) and sodium nitroprusside- (SNP-) induced lipid peroxidation in rat testes were investigated in vitro. The results revealed that the extract was able to scavenge DPPH radical, chelate Fe(2+) and also had a high reducing power. Furthermore, the incubation of the testes tissue homogenate in the presence of FeSO(4) and SNP, respectively, caused a significant increase in the malondialdehyde (MDA) contents of the testes. However, the aqueous extract of the stem bark of C. populnea caused a significant decrease in the MDA contents of both Fe(2+) (EC(50) = 0.027 mg/mL) and SNP- (EC(50) = 0.22 mg/mL) induced lipid peroxidation in the rat testes homogenates in a dose-dependent manner. The water extractible phytochemicals from C. populnea protect the testes from oxidative stress and this could be attributed to their high antioxidant activity: DPPH-scavenging ability, Fe(2+)-chelating and -reducing power. Therefore, oxidatively stress in testes could be potentially managed/prevented by this plant.

山羊桃是一种植物,在世界上不同的地方有着无数的药用价值,是类胡萝卜素、三萜和抗坏血酸的良好来源。研究了白杨茎皮水提物对FeSO(4)和硝普钠(SNP-)诱导的大鼠睾丸脂质过氧化的体外抗氧化性能和抑制作用。结果表明,该提取物具有清除DPPH自由基、螯合Fe(2+)的能力,并具有较高的还原能力。此外,分别在FeSO(4)和SNP存在下孵育睾丸组织匀浆,导致睾丸丙二醛(MDA)含量显著增加。而山茱萸茎皮水提物可显著降低大鼠睾丸均质液中Fe(2+) (EC(50) = 0.027 mg/mL)和SNP- (EC(50) = 0.22 mg/mL)诱导的脂质过氧化MDA含量,并呈剂量依赖性。水提植物化学物质可保护睾丸免受氧化应激,这可能归因于其高抗氧化活性:清除dpph的能力,铁(2+)螯合和还原能力。因此,该植物可以潜在地管理/预防睾丸氧化应激。
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引用次数: 15
Bioequivalence Study of Pantoprazole Sodium-HPBCD and Conventional Pantoprazole Sodium Enteric-Coated Tablet Formulations. 泮托拉唑钠- hpbcd与常规泮托拉唑钠肠溶片的生物等效性研究。
Pub Date : 2013-01-01 Epub Date: 2013-02-07 DOI: 10.1155/2013/347457
Sandesh P Kamdi, Prashant J Palkar

The objective of this study was to investigate the bioequivalence of two formulations of 40 mg pantoprazole sodium enteric-coated tablets: Tripepsa as the test and Pantocid as the reference. The two products were administered as a single oral dose according to a randomized two-phase crossover with a 1-month washout period in 25 healthy Indian volunteers. After drug administration, serial blood samples were collected over a period of 30 hours. Plasma pantoprazole concentrations were measured by high-performance liquid chromatography with UV detection. Pharmacokinetic parameters were analyzed based on noncompartmental analysis. The logarithmically transformed data of AUC0-∞ and Cmax were analyzed for 90% confidence intervals (CI) using ANOVA. The mean (90% CI) values for the ratio of AUC0-∞ and Cmax values of the test product over those of the reference product were 90.21 (83.69-97.24) and 108.68 (100.21-117.86), respectively (within the bioequivalence range of 80-125%). On the basis of pharmacokinetic parameters including AUC0-∞ , AUC0-t , and Cmax values, both the formulations were bioequivalent.

本研究的目的是考察泮托拉唑钠肠溶片40mg两种剂型的生物等效性:以三pepsa为对照,以Pantocid为对照。在25名健康的印度志愿者中,根据随机两期交叉和1个月的洗脱期,这两种产品作为单次口服剂量给药。给药后,在30小时内收集了一系列血液样本。采用高效液相色谱-紫外检测法测定泮托拉唑血浆浓度。采用非区室分析方法对药代动力学参数进行分析。对数变换后的AUC0-∞和Cmax数据使用方差分析(ANOVA)进行90%置信区间(CI)分析。试验产品与对照产品AUC0-∞和Cmax比值的均值(90% CI)分别为90.21(83.69 ~ 97.24)和108.68(100.21 ~ 117.86)(生物等效性范围为80 ~ 125%)。通过AUC0-∞、AUC0-t、Cmax等药代动力学参数分析,两种制剂均具有生物等效性。
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引用次数: 3
Comparison of Efficacy and Safety of Rosuvastatin, Atorvastatin and Pravastatin among Dyslipidemic Diabetic Patients. 瑞舒伐他汀、阿托伐他汀和普伐他汀治疗血脂异常糖尿病的疗效和安全性比较。
Pub Date : 2013-01-01 Epub Date: 2013-02-10 DOI: 10.1155/2013/146579
Lolwa Barakat, Amin Jayyousi, Abdulbari Bener, Bilal Zuby, Mahmoud Zirie

Objectives. To investigate the efficacy and the safety of the three most commonly prescribed statins (rosuvastatin, atorvastatin, and pravastatin) for managing dyslipidemia among diabetic patients in Qatar. Subjects and Methods. This retrospective observational population-based study included 350 consecutive diabetes patients who were diagnosed with dyslipidemia and prescribed any of the indicated statins between September 2005 and September 2009. Data was collected by review of the Pharmacy Database, the Electronic Medical Records Database (EMR viewer), and the Patient's Medical Records. Comparisons of lipid profile measurements at baseline and at first- and second-year intervals were taken. Results. Rosuvastatin (10 mg) was the most effective at reducing LDL-C (29.03%). Atorvastatin reduced LDL-C the most at a dose of 40 mg (22.8%), and pravastatin reduced LDL-C the most at a dose of 20 mg (20.3%). All three statins were safe in relation to muscular and hepatic functions. In relation to renal function, atorvastatin was the safest statin as it resulted in the least number of patients at the end of 2 years of treatment with the new onset of microalbuminuria (10.9%) followed by rosuvastatin (14.3%) and then pravastatin (26.6%). Conclusion. In the Qatari context, the most effective statin at reducing LDL-C was rosuvastatin 10 mg. Atorvastatin was the safest statin in relation to renal function. Future large-scale prospective studies are needed to confirm these results.

目标。研究三种最常用的他汀类药物(瑞舒伐他汀、阿托伐他汀和普伐他汀)治疗卡塔尔糖尿病患者血脂异常的有效性和安全性。研究对象和方法。这项基于人群的回顾性观察性研究纳入了350名连续的糖尿病患者,这些患者在2005年9月至2009年9月期间被诊断为血脂异常并服用了他汀类药物。数据是通过审查药房数据库、电子病历数据库(EMR查看器)和患者病历收集的。比较基线、第一年和第二年的血脂测量值。结果。瑞舒伐他汀(10 mg)在降低LDL-C方面最有效(29.03%)。阿托伐他汀在40mg剂量时降低LDL-C最多(22.8%),普伐他汀在20mg剂量时降低LDL-C最多(20.3%)。这三种他汀类药物对肌肉和肝功能都是安全的。在肾功能方面,阿托伐他汀是最安全的他汀类药物,因为在2年治疗结束时,新发微量白蛋白尿的患者人数最少(10.9%),其次是瑞舒伐他汀(14.3%),然后是普伐他汀(26.6%)。结论。在卡塔尔,降低LDL-C最有效的他汀类药物是瑞舒伐他汀10mg。阿托伐他汀是对肾功能最安全的他汀类药物。需要进一步的大规模前瞻性研究来证实这些结果。
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引用次数: 43
Comparative cytochrome p450 in vitro inhibition by atypical antipsychotic drugs. 非典型抗精神病药物对细胞色素p450体外抑制作用的比较。
Pub Date : 2013-01-01 Epub Date: 2013-02-13 DOI: 10.1155/2013/792456
Guillermo Gervasini, Maria J Caballero, Juan A Carrillo, Julio Benitez

The goal of this study was to assess in human liver microsomes the inhibitory capacity of commonly used antipsychotics on the most prominent CYP450 drug metabolizing enzymes (CYP1A2, CYP2C9, CYP2D6, and CYP3A). Chlorpromazine was the only antipsychotic that inhibited CYP1A2 activity (IC50 = 9.5  μ M), whilst levomepromazine, chlorpromazine, and thioridazine significantly decreased CYP2D6-mediated formation of 1'-hydroxybufuralol (IC50 range, 3.5-25.5  μ M). Olanzapine inhibited CYP3A-catalyzed production of 1', and 4'-hydroxymidazolam (IC50 = 14.65 and 42.20  μ M, resp.). In contrast, risperidone (IC50 = 20.7  μ M) and levomepromazine (IC50 = 30  μ M) showed selectivity towards the inhibition of midazolam 1'-hydroxylation reaction, and haloperidol did so towards 4'-hydroxylation (IC50 of 2.76  μ M). Thioridazine displayed a Ki of 1.75  μ M and an inhibitory potency of 1.57 on CYP2D6, suggesting a potential to induce in vivo interactions. However, with this exception, and given the observed Ki values, the potential of the assayed antipsychotics to produce clinically significant inhibitions of CYP450 isoforms in vivo seems limited.

本研究的目的是评估在人肝微粒体中常用抗精神病药物对最重要的CYP450药物代谢酶(CYP1A2、CYP2C9、CYP2D6和CYP3A)的抑制能力。氯丙嗪是唯一抑制CYP1A2活性的抗精神病药(IC50 = 9.5 μ M),而左旋丙嗪、氯丙嗪和硫唑嗪显著降低cyp2d6介导的1′-羟基丁胺醇的生成(IC50范围为3.5 ~ 25.5 μ M),奥氮平抑制cyp3a催化的1′、4′-羟基咪唑仑的生成(IC50分别为14.65和42.20 μ M)。相比而言,利培酮(IC50 = 20.7 μ M)和左旋丙嗪(IC50 = 30 μ M)对咪达唑仑1′-羟基化反应有选择性抑制,氟哌啶醇对4′-羟基化反应有选择性抑制(IC50 = 2.76 μ M),硫硝嗪对CYP2D6的Ki值为1.75 μ M,抑制效力为1.57,表明可能诱导体内相互作用。然而,除了这个例外,考虑到观察到的Ki值,所测抗精神病药物在体内产生具有临床意义的CYP450亚型抑制的潜力似乎有限。
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引用次数: 15
Amelioration of collagen-induced arthritis in female dark agouti rats by glucosamine treatment. 葡萄糖胺对雌性黑鼠胶原诱导关节炎的改善作用。
Pub Date : 2013-01-01 Epub Date: 2013-02-14 DOI: 10.1155/2013/562905
Nagaraja Haleagrahara, Dulanthi Tudawe, Srikumar Chakravarthi, Ammu Kutty Radhakrishnan

The present study assessed the therapeutic efficacy of glucosamine hydrochloride against collagen-induced arthritis in female Dark Agouti rats (DA). Arthritis was induced by intradermaly injecting a collagen and complete Freund's adjuvant suspension at multiple sites in the rat at a dose of 4 mg/kg of body weight and thereafter followed by two more boosters of the same dose, after the 1st week and 2nd week of primary immunization. After 21 days from the day of primary immunization, the arthritic group rats were given oral supplementation of glucosamine hydrochloride at a dose of 300 mg/kg of body weight until day 45. The arthritic group treated with glucosamine hydrochloride from day 21 to day 45 showed significant reduction in arthritic histopathological changes of the joints, reduction in paw thickness and also a significant decrease in C-reactive protein and TNF-alpha in the serum. Treatment with 300 mg/kg of glucosamine hydrochloride was able to reverse the arthritic changes, hence suggesting that glucosamine has a therapeutic effect against collagen-induced arthritis.

本研究评价了盐酸氨基葡萄糖对雌性黑鼠胶原性关节炎的治疗效果。在初次免疫第1周和第2周后,在大鼠的多个部位皮内注射胶原蛋白和完全的弗氏佐剂悬液,剂量为4 mg/kg体重,然后再注射两种相同剂量的增强剂,诱导关节炎。自初次免疫之日起21 d后,关节炎组大鼠按300 mg/kg体重口服盐酸氨基葡萄糖至第45天。第21天至第45天给予盐酸氨基葡萄糖治疗的关节炎组关节的关节炎组织病理学改变明显减轻,足部厚度减少,血清中c反应蛋白和tnf - α含量明显降低。用300 mg/kg盐酸氨基葡萄糖治疗能够逆转关节炎的变化,因此表明氨基葡萄糖对胶原诱导的关节炎有治疗作用。
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引用次数: 8
Erratum to “Bedtime Single-Dose Prednisolone in Clinically Stable Rheumatoid Arthritis Patients" “临床稳定型类风湿关节炎患者睡前单剂量强的松龙”的勘误
Pub Date : 2012-09-23 DOI: 10.5402/2012/521976
M. Owlia, Golbarg Mehrpoor, Moneyreh Modares Mosadegh
Copyright © 2012 Mohammad Bagher Owlia et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. We would like to reorganize the authors' names in the paper entitled " Bedtime single-dose prednisolone in clinically stable rheumatoid arthritis patients " which is published on PubMed in a correct fashion as below:
版权所有©2012 Mohammad Bagher Owlia et al。这是一篇在知识共享署名许可下发布的开放获取文章,该许可允许在任何媒体上不受限制地使用、分发和复制,只要原始作品被适当引用。我们将发表在PubMed上的《床边单剂量强的松龙治疗临床稳定型类风湿关节炎患者》这篇论文的作者姓名重新整理如下:
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引用次数: 0
Short-Term Therapy with Rosiglitazone, a PPAR-γ Agonist, Improves Metabolic Profile and Vascular Function in Nonobese Lean Wistar Rats. 罗格列酮(一种PPAR-γ激动剂)短期治疗可改善非肥胖瘦Wistar大鼠的代谢谱和血管功能。
Pub Date : 2012-01-01 Epub Date: 2012-08-21 DOI: 10.5402/2012/130347
Mohammad M Naderali, Imose Itua, Abdul-Razak Abubakari, Ebrahim K Naderali

A number of preclinical and clinical studies have reported blood-pressure-lowering benefits of thiazolidinediones in diabetic subjects and animal models of diabetes. This study was designed to further elucidate vascular effects of rosiglitazone, on healthy nonobese, lean animals. Adult male Wistar rats were randomized and assigned to control and rosiglitazone-treated groups and were dosed daily with either vehicle or rosiglitazone (10 mg kg(-1) day(-1)) by oral gavage for 5 days. Compared with control group, rosiglitazone treatment significantly reduced plasma levels of triglycerides (>240%) and nonesterified free fatty acids (>268%) (both, P < 0.001). There were no changes in vascular contractility to KCl or noradrenaline between two groups. However, rosiglitazone therapy improved carbamylcholine-induced vasorelaxation (93 ± 3 % versus control 78 ± 2, P < 0.01) an effect which was abolished by L-NAME. There was no difference in sodium nitroprusside-induced vasorelaxation between the control and rosiglitazone-treated animals. These results indicate that short-term rosiglitazone therapy improves both metabolic profile and vascular function in lean rats. The vascular effect of rosiglitazone appears to be mediated by alteration in NO production possibly by activation of endothelial PPARγ. This increased NO production together with improved lipid profile may explain mechanism(s) of blood-pressure-lowering effects of thiazolidinediones on both human and experimental animals.

许多临床前和临床研究报道了噻唑烷二酮在糖尿病受试者和糖尿病动物模型中的降压作用。本研究旨在进一步阐明罗格列酮对健康、非肥胖、精瘦动物的血管作用。将成年雄性Wistar大鼠随机分为对照组和罗格列酮治疗组,每天给药或灌胃罗格列酮(10 mg kg(-1) day),连续5 d。与对照组相比,罗格列酮治疗显著降低血浆甘油三酯水平(>240%)和非酯化游离脂肪酸水平(>268%)(均P < 0.001)。两组间血管对KCl或去甲肾上腺素的收缩力无变化。然而,罗格列酮治疗可改善氨甲酰胆碱诱导的血管松弛(93±3%,对照组78±2%,P < 0.01),而L-NAME可消除这一作用。硝普钠诱导的血管松弛在对照组和罗格列酮处理的动物之间没有差异。这些结果表明,短期罗格列酮治疗可以改善瘦大鼠的代谢谱和血管功能。罗格列酮的血管效应似乎是通过内皮细胞PPARγ的激活而改变NO的产生而介导的。这种一氧化氮生成的增加以及血脂的改善可能解释了噻唑烷二酮类药物对人类和实验动物降血压作用的机制。
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引用次数: 1
Pharmacological Evaluation and Docking Studies of 3-Thiadiazolyl- and Thioxo-1,2,4-triazolylcoumarin Derivatives as Cholinesterase Inhibitors. 3-噻二唑基和硫氧-1,2,4-三唑基香豆素衍生物胆碱酯酶抑制剂的药理评价及对接研究。
Pub Date : 2012-01-01 Epub Date: 2012-08-16 DOI: 10.5402/2012/707932
Ahsan Raza, Aamer Saeed, Aliya Ibrar, Muhammad Muddassar, Aftab Ahmed Khan, Jamshed Iqbal

Inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) is considered a promising strategy for the treatment of Alzheimer's disease (AD). This research project aims to provide a comprehensive knowledge of newly synthesized coumarin analogues with anti-AD potential. In the present work a series of 3-thiadiazolyl- and thioxo-1,2,4-triazolylcoumarins derivatives were designed, synthesized, and tested as potent inhibitors of cholinesterases. These compounds were assayed against AChE from electrophorus electricus and rabbit; and BChE from horse serum and rabbit by Ellman's method using neostigmine methylsulphate and donepezil as reference drugs. Some of the assayed compounds proved to be potent inhibitors of AChE and BChE with K(i) values in the micromolar range. 4b was found to be the most active compound with K(i) value 0.028 ± 0.002 μM and higher selectivity for AChE/BChE. The ability of 4b to interact with AChE was further confirmed through computational studies, in which a primary binding was proved to occur at the active gorge site, and a secondary binding was revealed at the peripheral anionic site. Structure activity relationships of prepared compounds were also discussed.

抑制乙酰胆碱酯酶(AChE)和丁基胆碱酯酶(BChE)被认为是治疗阿尔茨海默病(AD)的一种有前途的策略。本研究项目旨在全面了解新合成的具有抗ad潜力的香豆素类似物。本研究设计、合成了一系列3-噻二唑基和硫氧-1,2,4-三唑基香豆素衍生物,并对其作为胆碱酯酶的有效抑制剂进行了实验。测定了这些化合物对豚鼠和家兔乙酰胆碱酯酶的抑制作用;以甲基硫酸新斯的明和多奈哌齐为对照药,采用Ellman法分别从马血清和兔血清中提取BChE。一些测定的化合物被证明是AChE和BChE的有效抑制剂,其K(i)值在微摩尔范围内。4b的K(i)值为0.028±0.002 μM,对AChE/BChE具有较高的选择性,是活性最高的化合物。通过计算研究进一步证实了4b与AChE相互作用的能力,其中证明了在活性峡谷位点发生一次结合,并在外周阴离子位点发现了二次结合。并讨论了所制备化合物的构效关系。
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引用次数: 14
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