A Double-Blind, Placebo-Controlled, Cross Over Study Using a Latin Square Design to Evaluate the Safety, Tolerability, and Efficacy of NGX267 Oral Capsules in Patients With Xerostomia Associated With Sjogren's Syndrome

The purpose of this study is to evaluate the effectiveness of NGX267 in the improvement of decreased salivary flow associated with primary or secondary Sjögren's syndrome.
For each patient, the study includes four periods of treatment separated by a washout period that may range from 4 - 8 days according to patient and site discretion. Each treatment period includes two overnight stays in the clinic. One dose of study drug is taken during each treatment period

开始日期2008-02-01

申办/合作机构

TorreyPines Therapeutics, Inc.

100 项与 NGX-267 相关的临床结果

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100 项与 NGX-267 相关的转化医学

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项与 NGX-267 相关的文献（医药）

2021-07-13·ACS omega3区 · 化学

Mycobacterium tuberculosis Cell Wall Permeability Model Generation Using Chemoinformatics and Machine Learning Approaches

3区 · 化学

ArticleOA

作者: Nagamani, Selvaraman ; Sastry, G. Narahari

Abstract:

The drug-resistant strains of Mycobacterium tuberculosis (M.tb) are evolving at an alarming rate, and this indicates the urgent need for the development of novel antitubercular drugs. However, genetic mutations, complex cell wall system of M.tb, and influx–efflux transporter systems are the major permeability barriers that significantly affect the M.tb drugs activity. Thus, most of the small molecules are ineffective to arrest the M.tb cell growth, even though they are effective at the cellular level. To address the permeability issue, different machine learning models that effectively distinguish permeable and impermeable compounds were developed. The enzyme-based (IC50) and cell-based (minimal inhibitory concentration) data were considered for the classification of M.tb permeable and impermeable compounds. It was assumed that the compounds that have high activity in both enzyme-based and cell-based assays possess the required M.tb cell wall permeability. The XGBoost model was outperformed when compared to the other models generated from different algorithms such as random forest, support vector machine, and naïve Bayes. The XGBoost model was further validated using the validation data set (21 permeable and 19 impermeable compounds). The obtained machine learning models suggested that various descriptors such as molecular weight, atom type, electrotopological state, hydrogen bond donor/acceptor counts, and extended topochemical atoms of molecules are the major determining factors for both M.tb cell permeability and inhibitory activity. Furthermore, potential antimycobacterial drugs were identified using computational drug repurposing. All the approved drugs from DrugBank were collected and screened using the developed permeability model. The screened compounds were given as input in the PASS server for the identification of possible antimycobacterial compounds. The drugs that were retained after two filters were docked to the active site of 10 different potential antimycobacterial drug targets. The results obtained from this study may improve the understanding of M.tb permeability and activity that may aid in the development of novel antimycobacterial drugs.

2016-01-01·Neuro-degenerative diseases4区 · 医学

AF710B, a Novel M1/σ1 Agonist with Therapeutic Efficacy in Animal Models of Alzheimer's Disease

4区 · 医学

Article

作者: Brandeis, Rachel ; Fisher, Abraham ; Medeiros, Rodrigo ; Bar-Ner, Nira ; Ryskamp, Daniel A. ; Elkon, Hanoch ; Natan, Niva ; La Ferla, Frank M. ; Bezprozvanny, Ilya ; Wu, Lili ; Gershonov, Eitan ; Nahum, Victoria

We previously developed orthosteric M1 muscarinic agonists (e.g. AF102B, AF267B and AF292), which act as cognitive enhancers and potential disease modifiers. We now report on a novel compound, AF710B, a highly potent and selective allosteric M1 muscarinic and σ1 receptor agonist. AF710B exhibits an allosteric agonistic profile on the M1 muscarinic receptor; very low concentrations of AF710B significantly potentiated the binding and efficacy of carbachol on M1 receptors and their downstream effects (p-ERK1/2, p-CREB). AF710B (1-30 µg/kg, p.o.) was a potent and safe cognitive enhancer in rats treated with the M1 antagonist trihexyphenidyl (passive avoidance impairment). These effects of AF710B involve σ1 receptor activation. In agreement with its antiamnesic properties, AF710B (at 30 nM), via activation of M1 and a possible involvement of σ1 receptors, rescued mushroom synapse loss in PS1-KI and APP-KI neuronal cultures, while AF267B (1 µM) was less potent in PS1-KI and ineffective in APP-KI models, respectively. In female 3xTg-AD mice, AF710B (10 µg/kg, i.p./daily/2 months) (i) mitigated cognitive impairments in the Morris water maze; (ii) decreased BACE1, GSK3β activity, p25/CDK5, neuroinflammation, soluble and insoluble Aβ₄₀, Aβ₄₂, plaques and tau pathologies. AF710B differs from conventional σ1 and M1 muscarinic (orthosteric, allosteric or bitopic) agonists. These results highlight AF710B as a potential treatment for Alzheimer's disease (e.g. improving cognitive deficits, synaptic loss, amyloid and tau pathologies, and neuroinflammation) with a superior profile over a plethora of other therapeutic strategies.

2009-09-15·Proceedings of the National Academy of Sciences of the United States of America1区 · 综合性期刊

CKIε/δ-dependent phosphorylation is a temperature-insensitive, period-determining process in the mammalian circadian clock

1区 · 综合性期刊

Article

作者: Kojima, Toshio ; Ukai-Tadenuma, Maki ; Kishimoto, Wataru ; Fujishima, Hiroshi ; Nagai, Katsuya ; Shimomura, Kazuhiro ; Nakajima, Masato ; Sakaki, Yoshiyuki ; Ukai, Hideki ; Yamada, Rikuhiro G. ; Ishida, Mayumi ; Takano, Atsuko ; Kiuchi, Reiko ; Minami, Yoichi ; Ueda, Hiroki R. ; Masumoto, Koh-hei ; Takahashi, Joseph S. ; Kito, Ryotaku ; Yoo, Seung-Hee ; Takao, Toshifumi ; Isojima, Yasushi ; Nakao, Kazuki

A striking feature of the circadian clock is its flexible yet robust response to various environmental conditions. To analyze the biochemical processes underlying this flexible-yet-robust characteristic, we examined the effects of 1,260 pharmacologically active compounds in mouse and human clock cell lines. Compounds that markedly (>10 s.d.) lengthened the period in both cell lines, also lengthened it in central clock tissues and peripheral clock cells. Most compounds inhibited casein kinase Iε (CKIε) or CKIδ phosphorylation of the PER2 protein. Manipulation of CKIε/δ-dependent phosphorylation by these compounds lengthened the period of the mammalian clock from circadian (24 h) to circabidian (48 h), revealing its high sensitivity to chemical perturbation. The degradation rate of PER2, which is regulated by CKIε/δ-dependent phosphorylation, was temperature-insensitive in living clock cells, yet sensitive to chemical perturbations. This temperature-insensitivity was preserved in the CKIε/δ-dependent phosphorylation of a synthetic peptide in vitro. Thus, CKIε/δ-dependent phosphorylation is likely a temperature-insensitive period-determining process in the mammalian circadian clock.

项与 NGX-267 相关的新闻（医药）

2026-10-23

·Pharm-Patent

GLK-321(Glaukos)研究进展（V1,2026.10.23更新）

1、研究机构：Glaukos Corporation 2、别名：Antilirium、Eserine Salicylate、Eserine、Physostol、Synapton SR、Xalieve 3、靶点：ACHE 4、剂型及给药途径：眼膏剂; 眼部给药 5、结构式 6、适应症及进展适应症进展最新进展日期睑缘炎 II期 2026-06-25 7、研究历程 2025年12月05日，由Glaukos Corp在美国开展临床二期试验，用于治疗蠕形螨性睑缘炎。（NCT07400965） 8、临床试验登记号试验标题试验药适应症原始适应症申办/合作机构试验状态试验分期开始日期完成日期国家/地区 NCT07400965 Multicenter, Randomized, Double-Masked, Placebo-Controlled, Parallel Group Phase 2 Trial Evaluating the Safety and Efficacy of GLK-321 in Subjects With Demodex Blepharitis 水杨酸毒扁豆碱 (to both eyes) 睑缘炎 Demodex Blepharitis Glaukos Corp. Recruiting 临床2期 2025-12-05 2026-11-01 美国 ISRCTN62968791 A double-blind investigation of the effects of daily applications of the physostigmine and hyoscine transdermal patch (NAPS2 F11/21) with an armband on the pharmacokinetic (PK), pharmacodynamic (PD) and safety profiles over a 21-day period in healthy male and female Caucasian subjects 氢溴酸东莨菪碱 | 水杨酸毒扁豆碱 - Potential risk of poisoning by nerve agent Injury, Occupational Diseases, Poisoning - Completed 临床1期 2009-01-27 2012-07-17 英国 ISRCTN13607674 An investigation of the effects of an armband applied over the F11/21 physostigmine and hyoscine transdermal patch on pharmacokinetic, pharmacodynamic and safety profiles in healthy male subjects 氢溴酸东莨菪碱 | 水杨酸毒扁豆碱 - Potential risk of poisoning by nerve agent Injury, Occupational Diseases, Poisoning - Completed 临床2期 2008-03-06 2011-02-15 英国 ISRCTN78730348 A randomised, double-blind, placebo-controlled, crossover, dose escalation study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of physostigmine salicylate and hyoscine hydrobromide by continuous, intravenous infusion to healthy Caucasian male and female volunteers, given separately and in combination. 丁溴东莨菪碱 | 水杨酸毒扁豆碱 - Potential risk of poisoning by nerve agent Injury, Occupational Diseases, Poisoning - Completed 临床1期 2011-11-09 2016-01-20 英国 ISRCTN15358284 A study to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of a single application (one or two dose levels) and multiple applications (one dose level) of the transdermal patch formulations of physostigmine and hyoscine in healthy female subjects 氢溴酸东莨菪碱 | 水杨酸毒扁豆碱 - Potential risk of poisoning by nerve agent Injury, Occupational Diseases, Poisoning The Defence Science & Technology Laboratory Completed 临床1期 2007-03-19 2008-11-12 英国 ISRCTN79173829 A two-part study to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple applications of the F11/25 transdermal patch formulation of hyoscine and physostigmine in healthy male participants 氢溴酸东莨菪碱 | 水杨酸毒扁豆碱 - Potential risk of poisoning by nerve agent Injury, Occupational Diseases, Poisoning - Completed 临床1期 2006-10-16 2008-04-22 英国 ISRCTN73285902 A Randomised, Double-Blind, Placebo-Controlled, Crossover Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of a Single Application of a Transdermal Patch Formulation of Hyoscine and Physostigmine in Healthy Male Subjects with Pigmented Skin of Grade 5 on the Fitzpatrick Skin Scale 氢溴酸东莨菪碱 | 水杨酸毒扁豆碱 - Potential risk of poisoning by nerve agent Injury, Occupational Diseases, Poisoning - Completed 临床1期 2006-02-14 2007-04-23 英国 ISRCTN16859029 A Two-part Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Applications of Four Transdermal Patch Formulations of Hyoscine and Physostigmine in Healthy Male Participants 氢溴酸东莨菪碱 | 水杨酸毒扁豆碱 - Potential risk of poisoning by nerve agent Injury, Occupational Diseases, Poisoning - Completed 临床2期 2005-10-12 2007-01-17 英国 ISRCTN29062676 A Dose-escalation Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Four Transdermal Patch Formulations (F4-F7) of Hyoscine and Physostigmine in Healthy Male Subjects 氢溴酸东莨菪碱 | 水杨酸毒扁豆碱 - Potential risk of poisoning by nerve agent Injury, Occupational Diseases, Poisoning Poisoning - Completed 临床1期 2005-01-13 2006-05-30 英国 ISRCTN21827000 A randomised, double-blind, three-way crossover study to investigate the pharmacokinetics, pharmacodynamics, safety and tolerability after single applications of three transdermal patch formulations of physostigmine and hyoscine in healthy males 氢溴酸东莨菪碱 | 水杨酸毒扁豆碱 - Potential risk of poisoning by nerve agent Injury, Occupational Diseases, Poisoning The Defence Science & Technology Laboratory Completed 临床1期 2004-04-28 2004-12-13 英国 ISRCTN10362655 An open, replicate, two-period, single and multiple-dose, pharmacokinetic and tolerability study of the PHP (150 g/m2) transdermal patch containing physostigmine and hyoscine in healthy, adult Caucasian males. 氢溴酸东莨菪碱 | 水杨酸毒扁豆碱 - Potential risk of poisoning by nerve agent Injury, Occupational Diseases, Poisoning The Defence Science & Technology Laboratory Completed 临床1期 2014-02-11 2014-06-04 英国 NCT03090620 A Randomized Trial Comparing Physostigmine vs Lorazepam for Treatment of Adolescent Antimuscarinic (Anticholinergic) Toxidrome 水杨酸毒扁豆碱 | 劳拉西泮毒性 Anticholinergics Toxicity University of Colorado Denver | American Academy of Clinical Toxicology Completed 临床4期 2017-03-30 2020-08-31 美国 NCT03013322 Anticholium® Per Se a Randomized, Double-blind, Placebo-controlled, Monocentric Trial on the Adjunctive Use of Physostigmine Salicylate (Anticholium®) in Perioperative Sepsis and Septic Shock 水杨酸毒扁豆碱脓毒性休克 Shock, Septic | Sepsis | Perioperative Period University Hospital Heidelberg Completed N/A 2015-01-28 2017-02-18 德国 NCT02216266 Monocenter, Double Blind, Randomised, Placebo Controlled Study to Evaluate Physostigmine for the Treatment of Delirium in Perioperative Intensive Care Medicine 水杨酸毒扁豆碱谵妄 Suspected Delirium After Elective or Emergency Heart Surgery | CAM-ICU Diagnosed Delirium Hospital of the Johann Wolfgang Goethe University | Dr. Franz Köhler Chemie GmbH | Johann Wolfgang Goethe-Universität Frankfurt am Main Unknown status 临床3期 2014-04-01 2018-12-01 德国 NCT02008292 Acetylcholine, Tobacco Smoking, Genes and Nicotinic Receptors 水杨酸毒扁豆碱吸烟 | 精神分裂症 Smoking | Schizophrenia Yale University | National Institutes of Health | National Institute on Drug Abuse Completed N/A 2013-09-01 2021-12-01 美国 NCT01394445 Influence of Physostigmine on Patient-Controlled Analgesia 水杨酸毒扁豆碱术后疼痛 Postoperative Pain Medizinische Universität Graz Completed 临床3期 2011-06-01 2011-12-01 奥地利 NCT01171118 Phamacological Reversal of Airway Instability During Sedation 水杨酸毒扁豆碱气道阻塞 Upper Airway Obstruction University of Rochester Completed N/A 2009-08-01 2011-08-01 美国 NCT01121497 The Effect of Physostigmine on Cognitive Functioning in the Immediate Period After Sedation for Colonoscopy 水杨酸毒扁豆碱认知功能障碍 Cognitive Dysfunction Rabin Medical Center Beilinson Unknown status N/A 2010-07-01 2011-07-01 以色列 NCT00850850 The Use of Physostigmine in Elderly Patients in the Postoperative Recovery-phase After General Anesthesia 水杨酸毒扁豆碱麻醉 | 术后恶心呕吐 Postoperative Nausea and Vomiting | Anesthesia Recovery Period Bispebjerg Hospital Unknown status N/A 2009-12-01 2011-05-01 丹麦 NCT00689208 Pharmacological Intervention in Insulin Resistance Targeting Autonomic Nerve Activity - a Concept Study in Mani 水杨酸毒扁豆碱 | 硫酸阿托品胰岛素抵抗 Insulin Resistance AstraZeneca PLC Completed 早期临床1期 2007-05-01 2008-11-01 瑞典 EUCTR2005-006017-41-SE A single-centre, placebo-controlled, cross-over, double blind study of the effects on salivation by increasing doses of physostigmine applied to the labial mucosa of subjects with chronic dry mouth symptoms. A phase II dose-finding study. 水杨酸毒扁豆碱 (口腔黏膜溶液, 口腔粘膜给药) 口干症 Chronic dry mouth Calabar AB Completed 临床2期 2006-02-06 - 瑞典 9、临床结果标题登记号来源分期适应症评价人数用药方案结果评价发布日期申办/合作机构主要研究药物来源链接 Synapse链接 Acetylcholine, Tobacco Smoking, Genes and Nicotinic Receptors NCT02008292 CTgov N/A 吸烟 | 精神分裂症 80 Physostigmine(ACH Levels in Healthy Controls After Physostigmine Administration) Change in Acetylcholine (ACh) Levels After Physostigmine Administration as Confirmed by PET Images.(Mean) = 5.9 % - 2023-02-06 Yale University | National Institutes of Health | National Institute on Drug Abuse 水杨酸毒扁豆碱 https://clinicaltrials.gov/ct2/show/results/NCT02008292 https://synapse.zhihuiya.com/clinical-result-detail/aa00345da024a058548e2205a5989050 Acetylcholine, Tobacco Smoking, Genes and Nicotinic Receptors NCT02008292 CTgov N/A 吸烟 | 精神分裂症 80 Physostigmine(ACH Levels in Smokers After Physostigmine Administration) Change in Acetylcholine (ACh) Levels After Physostigmine Administration as Confirmed by PET Images.(Mean) = 4.3 % - 2023-02-06 Yale University | National Institutes of Health | National Institute on Drug Abuse 水杨酸毒扁豆碱 https://clinicaltrials.gov/ct2/show/results/NCT02008292 https://synapse.zhihuiya.com/clinical-result-detail/aa00345da024a058548e2205a5989050 A Randomized Trial Comparing Physostigmine vs Lorazepam for Treatment of Adolescent Antimuscarinic (Anticholinergic) Toxidrome NCT03090620 CTgov 临床4期毒性 19 Physostigmine(Physostigmine) Comparison of RASS Score Between Physostigmine and Lorazepam: Before Bolus(Median) = 1.5 Point (IQR, 1 ~ 2) - 2021-08-23 University of Colorado Denver | American Academy of Clinical Toxicology 水杨酸毒扁豆碱 | 劳拉西泮 https://clinicaltrials.gov/ct2/show/results/NCT03090620 https://synapse.zhihuiya.com/clinical-result-detail/204e0d835d420490d5e90250ae2a2555 A Randomized Trial Comparing Physostigmine vs Lorazepam for Treatment of Adolescent Antimuscarinic (Anticholinergic) Toxidrome NCT03090620 CTgov 临床4期毒性 19 Lorazepam(Lorazepam) Comparison of RASS Score Between Physostigmine and Lorazepam: Before Bolus(Median) = 1 Point (IQR, 1 ~ 1.5) - 2021-08-23 University of Colorado Denver | American Academy of Clinical Toxicology 水杨酸毒扁豆碱 | 劳拉西泮 https://clinicaltrials.gov/ct2/show/results/NCT03090620 https://synapse.zhihuiya.com/clinical-result-detail/204e0d835d420490d5e90250ae2a2555 10、转化医学研究亮点主题期刊/会议出版日期药物适应症机构 Physostigmine modulates hippocampal GABAergic neurotransmission via α7 nicotinic acetylcholine receptors - 药物发现/临床前 Neuropharmacology 2026-02-01 水杨酸毒扁豆碱 - Universidad Nacional Autónoma de México Amyloid-beta's disruption of hippocampal neuronal circuit function depends upon behavioral state - 药物发现/临床前 SFN 2022 2022-11-16 水杨酸毒扁豆碱阿尔茨海默症 Massachusetts Gen. Hosp. In vivo dose–response analysis to acetylcholine: pharmacodynamic assessment by polarized reflectance spectroscopy - 药物发现/临床前 Pubmed 2022-04-21 水杨酸毒扁豆碱 - University of Linköping | Department of Biomedical and Clinical Sciences, Faculty of Health Sciences, Linköping University, Linköping, Sweden. Joakim.henricson@liu.se. | Department of Emergency Medicine, Local Health Care Services in Central Östergötland, 58182, Linköping, Sweden. Joakim.henricson@liu.se. An acetylcholine-dopamine interaction in the rat nucleus accumbens and its tentative involvement in ethanol's dopamine-liberating effect 酒精使用障碍是一种与严重医学后果相关的慢性、复发性脑疾病，可能导致早逝。尽管数量不多，但胆碱能神经元（CIN）在核子底丘（nAc）中已被认为是可能对多巴胺（DA）神经传导产生调节影响的重要细胞群。CIN的缺陷被认为与精神疾病如酒精成瘾有关。本研究旨在研究乙酰胆碱（ACh）是否可以在nAc局部影响DA的释放，以及通过哪种受体群介导这种效应。此外，我们还想确定ACh在乙醇诱导的DA升高中的作用。研究结果表明，ACh在nAc中增加细胞外DA水平，这一效应是通过毒蕈碱ACh受体介导的，而不是通过尼古丁ACh受体介导的。考虑到毒蕈碱在一定程度上减弱了乙醇诱导的DA输出，以及CIN的损伤似乎阻碍了对乙醇的DA释放，nAc中来自CIN的ACh释放可能部分参与了乙醇诱导的nAc中的DA释放。药物发现/临床前 SFN 2019 2019-10-19 水杨酸毒扁豆碱酗酒 Beroendekliniken, Sahlgrenska Univ. Hosp., Gothenburg, Sweden | Addiction Biol. Unit, Dept. of Psychiatry and Neurochemistry, Univ. of Gothenburg, Gothenburg, Sweden Optogenetic activation of mouse airway parasympathetic neurons to provoke bronchoconstriction - 药物发现/临床前 ERS 2019 2019-09-28 水杨酸毒扁豆碱 | 硫酸阿托品哮喘 Oregon Health & Science University, Portland, United States of America Acetylcholinergic mechanisms of depressive-like behaviors induced by seasonally-relevant short active photoperiod 季节相关的短活跃光周期诱发的抑郁样行为的乙酰胆碱机制。摘要：环境因素，如白天长度的季节变化，可以以特定方向影响双相情感障碍（BD）患者情绪状态的转换。与季节性情感障碍患者一致，BD患者在秋季和冬季（短活跃；SA）光周期减少时表现出抑郁发作。小鼠和大鼠在SA光周期下也表现出类似效应。通过乙酰胆碱酯酶（AChE）抑制剂生理斯的明（PHYSO）诱导乙酰胆碱的药理学增加会导致BD患者抑郁，并在小鼠中诱发抑郁相关行为。我们的研究结果表明乙酰胆碱神经传导在暴露于SA光周期后表达抑郁样行为中起着关键作用。进行中的实验将尝试使用体内微透析验证SA光周期暴露后海马中乙酰胆碱水平的增加，以及病毒传递的外源人类AChE是否能够阻断这种效应的表达。药物发现/临床前 SFN 2018 2018-11-07 水杨酸毒扁豆碱 - Department of Psychiatry | Univ. of California San Diego, La Jolla, CA Effort-related choice behavior is regulated by cholinergic signaling in the ventral tegmental area 本研究发现，VTA中的胆碱能信号调节了与努力相关的选择行为。这一发现揭示了胆碱能信号在调节奖励驱动行为中的重要作用，为进一步研究胆碱能信号在VTA中特定受体的作用提供了新的方向。这对于理解抑郁症等疾病中动机缺失的病理机制具有重要意义。药物发现/临床前 SFN 2018 2018-11-06 水杨酸毒扁豆碱 - Psychiatry, Yale Univ., New Haven, CT Cholinergic modulation on LTD in rat hippocampal network - 药物发现/临床前 SFN 2016 2016-11-14 水杨酸毒扁豆碱 learning and memory Tamagawa Univ. Grad. Sch. of Engin., Tokyo, Japan Cholinergic modulation of the parafacial respiratory group 该研究发现，位于脑干的呼吸节律生成器包括呼吸肌的主要驱动力量——呼吸前区复合体（preBötC）和呼吸后区呼吸群（pFRG）。pFRG在休息状态下保持沉默，但在呼吸驱动增加时会产生节律性活动。研究发现，乙酰胆碱在促进pFRG神经元激活和促进腹部肌肉活动方面发挥作用。实验证明，乙酰胆碱能够增强pFRG的活性，促进腹部肌肉的活动和呼气流量。这一发现对于了解呼吸调节机制具有重要意义。药物发现/临床前 SFN 2016 2016-11-14 水杨酸毒扁豆碱 - Physiol., Univ. of Alberta, Edmonton, AB, Canada Dissociative depression-related behavioral effects of cholinergic signaling in the ventral tegmental area versus the nucleus accumbens 本研究发现，VTA和NAc中的胆碱能信号参与调节抑郁相关行为。VTA和NAc中的胆碱受体能显著改变多种神经元群体的多巴胺活性，而多巴胺活性已知介导应激易感性。然而，目前尚不清楚VTA和NAc中的胆碱机制是否类似或不同地调节与抑郁相关的应激和焦虑行为。本研究的目标是确定VTA或NAc中胆碱能调节是否类似地影响各种抑郁相关行为。实验结果显示，VTA中的胆碱能增加易感性应激，而NAc中的胆碱能则具有抗抑郁样反应。这些发现为了解胆碱活性在抑郁相关行为中的作用提供了新的见解。药物发现/临床前 SFN 2015 2015-10-20 水杨酸毒扁豆碱 - Yale University | New Haven Cholinergic regulation of hippocampus-amygdala axis in depression-like and stress-related behavior 本研究探讨了乙酰胆碱酯酶（AChE）在大鼠海马和杏仁核中的调节作用，以及其对抑郁样行为和应激相关行为的影响。研究发现，海马中AChE活性的降低足以产生抑郁样行为，而尼古丁通过高亲和力的尼古丁ACh受体（nAChRs）对抑郁样症状产生影响。此外，研究还发现乙酰胆碱在杏仁核中的高活性可能对通过海马介导的抑郁样行为具有许可作用。这些研究表明，多个脑区的乙酰胆碱信号可以影响大鼠的抑郁样行为，海马和杏仁核之间的相互作用可能对ACh对情绪和应激反应的调节至关重要。药物发现/临床前 SFN 2013 2013-11-13 水杨酸毒扁豆碱 - Yale Univ Parkinsonian tremor in middle aged rats: Effects of chronic vs. acute cholinergic activation 本研究探讨了长期和短期胆碱能激活对中年大鼠帕金森震颤的影响。结果显示，长期使用乙酰胆碱酯酶抑制剂会导致震颤运动症状的加重，包括静止性震颤。实验发现，长期使用乙酰胆碱酯酶抑制剂的大鼠出现了震颤运动的敏感性增加。此外，研究还发现，长期胆碱能激活会导致震颤的增加，这一发现强调了需要开发新的治疗方法，以减少或消除帕金森运动副作用。药物发现/临床前 SFN 2013 2013-11-12 水杨酸毒扁豆碱震颤 Univ. of Connecticut Cholinergic signaling in the hippocampus regulates social stress resilience and anxiety- and depression-like behavior 该研究发现，海马区的胆碱能信号调节社交压力的适应性和焦虑抑郁行为。通过给小鼠注射乙酰胆碱酯酶抑制剂物理斯亭，发现增加了焦虑和抑郁行为，而给予尼古丁或毒蕈碱拮抗剂可以逆转这种效应。抗抑郁药氟西汀也可以逆转物理斯亭的行为效应，并且增加了整个大脑的乙酰胆碱酯酶活性，尤其是在海马区。海马区的胆碱能信号对焦虑和抑郁行为有重要影响，而胆碱能系统的异常可能是情绪障碍的病因之一。靶点 Proc Natl Acad Sci U S A 2013-02-11 水杨酸毒扁豆碱 - Yale School of Medicine Evidence for a novel hypercholinergic model of anxiety and depression 这份文本提出了新的抑郁焦虑的高乙酰胆碱能模型的证据。通过使用AChE抑制剂physostigmine在小鼠身上实验，研究发现增加乙酰胆碱能活性会导致抑郁行为的增加，而经典抗抑郁药氟西汀可以逆转这一效应。此外，对海马体内AChE活性的调节也会影响情绪及焦虑行为。这些研究结果表明乙酰胆碱在海马体内对情绪和焦虑行为具有调节作用，并且shRNA介导的AChE水平降低可作为抑郁症样表型的新模型。这些发现证实了乙酰胆碱系统在特定抑郁症内源表型中的关键作用。药物发现/临床前 SFN 2012 2012-10-17 水杨酸毒扁豆碱 - Dept. of Mol. Psychiatry, Yale Univ. Sch. of Med Cholinergic adaptations in PRiMA-deficient mice PRiMA失活小鼠中胆碱适应性变化研究发现，相较野生型小鼠，PRiMA敲除小鼠纹状体乙酰胆碱酯酶（AChE）活性降低至仅为2-3％。研究发现PRiMA敲除小鼠外部纹状体乙酰胆碱（ACh）水平显著增加了280倍，而无明显表型。此外，AChE抑制剂导致ACh水平上升的实验支持PRiMA-AChE相互作用的抑制剂可能对治疗阿尔茨海默病中央胆碱功能障碍具有潜在作用。由于这些发现暗示PRiMA可能成为治疗胆碱能功能障碍的新靶点，而无严重副作用。药物发现/临床前 SFN 2012 2012-10-17 水杨酸毒扁豆碱阿尔茨海默症 Pharmacol., Goethe Univ., Frankfurt/Main, Germany; Functional convergence between the hippocampus and prefrontal cortex is critical for cholinergic-based recovery in the amnestic rat 本研究发现，海马和前额叶皮层之间的功能融合对于Korsakoff遗忘症大鼠的胆碱能恢复至关重要。我们使用了丁硫胺诱导的硫胺素缺乏（PTD）动物模型，发现海马和额叶皮层的乙酰胆碱（ACh）释放存在功能障碍。在行为测试中，海马和前额叶皮层的ACh释放呈强正相关，表明ACh活性对于这一回路的整合功能至关重要。此外，我们发现增加海马或前额叶皮层的胆碱能水平可以挽救PTD大鼠的行为障碍。我们的初步研究结果表明，激活PTD大鼠的前额皮层或海马可以显著增加对侧区域的胆碱活性，并且当两个区域在对侧同时被激活时，记忆表现得到改善。我们的研究结果表明，通过刺激胆碱能受体，促进海马和前额叶皮层之间的ACh释放，可以实现Korsakoff遗忘症大鼠的功能恢复。药物发现/临床前 SFN 2011 2011-11-16 水杨酸毒扁豆碱遗忘 Binghamton, NY; | Binghamton Univ., Binghamton, NY Manipulation of hippocampal acetylcholinesterase activity controls anxiety-and depression-like behaviors 本研究发现，改变海马乙酰胆碱酯酶（AChE）活性可以影响焦虑和抑郁行为。通过药物或基因干预，降低海马中AChE活性会导致抑郁和焦虑行为的加剧，而增加AChE活性则可以缓解这些负面效应。这些发现表明，调节胆碱能系统可能有望成为治疗抑郁和焦虑症状的新途径，同时也暗示了抗胆碱酯酶药物在对抗老年痴呆和帕金森病的同时，可能也对情绪调节产生积极影响。药物发现/临床前 SFN 2011 2011-11-15 水杨酸毒扁豆碱 - Dept Pyschiat, Yale Univ. Sch. Med Acetylcholine modulation on STDP in CA1 region of hippocampus 本研究探讨了乙酰胆碱对海马CA1区STDP的调节作用。研究发现，来自脑中隔的胆碱能够通过激活毛细胞受体产生慢性兴奋后电位，对突触可塑性产生影响。实验结果表明，胆碱能够增强正时STDP诱导的长时程增强，抑制负时STDP诱导的长时程抑制。此外，胆碱酯酶抑制剂能够增强STDP诱导的长时程增强，而胆碱过量则抑制STDP。这些结果表明，胆碱能够调节突触可塑性，对海马CA1锥体细胞的信息处理起着重要作用。药物发现/临床前 SFN 2011 2011-11-14 水杨酸毒扁豆碱 - Kawasaki Univ. of medical welfare, Kurashiki, Japan | Tamagawa Univ. Grad. Sch. of Engin., Tokyo, Japan; Reduced hippocampal acetylcholine efflux after medial septal-diagonal band (MSDB) GABAergic lesion is associated with impaired working memory: behavioral and neurochemical effects of physostigmine. 该研究发现，损伤GABA能MED扩散边缘-斜带（MSDB）神经元会导致空间工作记忆障碍，同时降低迷宫激活的海马ACh释放量。使用Acetylcholinesterase抑制剂physostigmine增加ACh释放并不能改善行为表现，这表明海马ACh可能不是影响DNMTP表现的关键因素。然而，如果physostigmine增加ACh释放并增强DNMTP表现，将支持MSDB胆碱能和GABA能神经元对DNMTP表现的重要性。这些研究结果表明了损伤MSDB GABA能神经元对工作记忆任务的影响，以及海马ACh释放是否在工作记忆障碍中起到了关键作用。药物发现/临床前 SFN 2011 2011-11-14 水杨酸毒扁豆碱 - SMBI, NJMS-UMDNJ, Newark, NJ; Binding sites for galanthamine and physostigmine in the Torpedo nicotinic acetylcholine receptor extracellular domain 本研究通过平衡放射配体结合分析、光致亲和标记和计算分析，研究了加兰他敏和丁斯丁官与鱼雷尖吻鳐尼古丁乙酰胆碱受体（nAChR）的相互作用。结果显示，加兰他敏和丁斯丁官在nAChR的激动剂结合α-γ和α-δ界面以及非激动剂结合δ-β界面中结合。在激动剂结合界面，加兰他敏和丁斯丁官结合到α亚单位的C段、γ亚单位的E段和δ亚单位的F段。此外，加兰他敏和丁斯丁官在nAChR的δ-β外部界面结合到δTyr212，而在存在激动剂时结合增强。研究还发现，加兰他敏和丁斯丁官以互斥的方式结合到nAChR的δ和β亚单位界面上，这个结合位点相当于GABAA受体的苯二氮䓬类药物位点。药物发现/临床前 SFN 2011 2011-11-14 水杨酸毒扁豆碱 | 氢溴酸加兰他敏 - Harvard Med. Sch Differential effects of the anticholinesterase physostigmine and the adenosine antagonist caffeine on memory encoding and retrieval in aged rats: interventions to reduce proactive interference - 药物发现/临床前 SFN 2011 2011-11-14 水杨酸毒扁豆碱 | 枸橼酸咖啡因认知功能障碍 | 痴呆 Psychology, Univ. of Connecticut, Storrs Manfld, CT Role of the cholinergic system for rhythmic brain activity in a spatial visual attention task 本研究通过使用脑磁图（MEG）测量，调查了胆碱能激动剂生理斯的明对节律性脑活动的影响。研究发现，生理斯的明影响了不同频率带的总体功率，并具有清晰的频率特异性和区域特异性。此外，生理斯的明还显著改变了不同脑区的刺激诱发扰动，揭示了高频和低频带之间的一些对抗关系。最后，生理斯的明还调节了特定频率带中的空间注意效应，主要发生在已建立的额顶-顶-顶网络节点，而不是视觉皮层本身。这些结果为胆碱能系统在体内节律性脑活动和注意功能中的作用提供了新的见解。药物发现/临床前 SFN 2010 2010-11-16 水杨酸毒扁豆碱 - Wellcome Trust Ctr. Neuroimaging UCL Protection against the neurotoxic effects of organophosphate poisoning without carbamate pretreatment in guinea pigs - 药物发现/临床前 SFN 2010 2010-11-16 丁溴东莨菪碱 | 水杨酸毒扁豆碱 | MMB-4 | IVIEW-1802 | 苯巴比妥有机磷中毒 USAMRICD, GUNPOWDER, MD Modulation of synaptic transmission in the hippocampal CA1 region by endogenous acetylcholine: Novel findings and approaches - 药物发现/临床前 SFN 2010 2010-11-15 盐酸美加明 | 水杨酸毒扁豆碱 - PhysIOL SA The effect of cholinergic inputs on STDP in hippocampal CA1 network 本研究探讨了乙酰胆碱输入对海马CA1网络中STDP的影响。研究发现，来自脑内隔的乙酰胆碱输入通过投射到海马CA1锥体神经元上的胆碱能受体，作为与动机相关的自上而下的输入。乙酰胆碱输入被认为与感觉输入、自下而上的输入整合，并在信息处理中发挥关键作用。研究还发现，前后突触间的相对时序决定了突触变化的方向和程度，即STDP，显示了自下而上的信息处理。正负相对时序分别诱导了LTP和LTD。研究结果表明，乙酰胆碱的强度调节了突触可塑性。这一研究揭示了海马CA1神经元中自上而下和自下而上信息整合的重要阶段。药物发现/临床前 SFN 2010 2010-11-14 水杨酸毒扁豆碱 - Tamagawa Univ. Grad. Sch. of Engin. Identification of a physostigmine binding site in the torpedo nicotinic acetylcholine receptor extracellular domain at the delta-beta subunit interface - 结构生物学 SFN 2010 2010-11-13 水杨酸毒扁豆碱阿尔茨海默症 | 重症肌无力 Harvard Med. Sch Increasing ACh efflux in the frontal cortex via acetylcholinesterase inhibitors alleviates diencephalic amnesia - 药物发现/临床前 SFN 2009 2009-10-21 水杨酸毒扁豆碱遗忘 Binghamton univ, Vestal, NY Effect of acetylcholine esterase activity on depression-like behaviors in mice 本研究探讨了乙酰胆碱酯酶（AChE）活性对小鼠抑郁样行为的影响。结果表明，通过阻断高亲和性尼古丁型乙酰胆碱受体（nAChRs）降低大脑胆碱能调节，可在人类和动物模型中产生类似抗抑郁药的效果。此外，实验结果还显示，体内AChE活性的增加可能导致类似抑郁的效果，而减少胆碱能信号则可能具有抗抑郁作用。研究发现，对小鼠进行AChE活性的干预后，产生了与抑郁样行为相关的结果。急性给药催发了类似抗抑郁的效果，而慢性给药则产生了抗抑郁效果。这些结果强烈暗示了胆碱能活性在抑郁症状的调节中至关重要。此外，这些研究结果还暗示了在阿尔茨海默病和帕金森病患者中使用AChE抑制剂可能导致情绪变化。药物发现/临床前 SFN 2009 2009-10-20 水杨酸毒扁豆碱 - Psychiatry, Yale Univ. Sch. Med Sexually diergic hypothalamic-pituitary-adrenal axis responses to acetylcholinesterase inhibitors in an in vitro perfusion system - 药物发现/临床前 SFN 2009 2009-10-17 水杨酸毒扁豆碱 | 盐酸他克林 | 氢溴酸加兰他敏阿尔茨海默症 Biol., St. Vincent Col., Latrobe, PA; | Psychiatry/Mental Hlth. (116A), VA Greater LA Healthcare Syst, Los Angeles, CA p249 PATHOPHYSIOLOGY OF ATTENUATION OF MYOCLONUS IN A CASE OF PROGRESSIVE MYOCLONUS EPILEPSY - 药物发现/临床前 IEC 2007 2007-07-07 水杨酸毒扁豆碱进行性肌阵挛性癫痫 National Center of Neurology & Psychiatry Physostigmine counteracts the inhibitory avoidance impairment produced by amitriptyline in mice 本研究发现三环抗抑郁药阿米替林对小鼠的抑制性（被动）规避记忆产生了损害。我们的目的是研究胆碱能激动剂毒扁豆碱对雄性和雌性CD1小鼠急性阿米替林注射产生的抑制性规避损害的可能调节作用。实验结果显示，单独使用阿米替林处理的雄性和雌性小鼠完全缺乏抑制性规避学习，而同时使用阿米替林和毒扁豆碱处理的小鼠观察到了类似对照组的抑制性规避学习。这些结果表明胆碱能系统参与了阿米替林对小鼠抑制性规避学习的损害。药物发现/临床前 SFN 2006 2006-10-15 水杨酸毒扁豆碱 inhibitory avoidance impairment Univ Valencia Increasing hippocampal acetylcholine release enhances behavioral performance in an animal model of diencephalic amnesia 本实验研究了乙酰胆碱酯酶抑制剂对Wernicke-Korsakoff综合症小鼠模型的行为和神经化学变化的影响。结果显示，乙酰胆碱酯酶抑制剂能够增加海马乙酰胆碱释放，改善行为表现，消除学习和记忆障碍。此外，乙酰胆碱的增加可能通过激活扩展海马系统和海马周围通路，提高空间学习能力。药物发现/临床前 SFN 2006 2006-10-15 水杨酸毒扁豆碱遗忘 Psychology, Univ Binghamton, Binghamton, NY. The effects of cholinergic agonists on spatial working memory in rats with hippocampal damage. - 药物发现/临床前 SFN 2005 2005-11-16 尼古丁 | 水杨酸毒扁豆碱 | 盐酸他克林记忆障碍 Northern Kentucky Univ. Acetylcholinesterase inhibitor physostigmine enhances basal dendritic long-term potentiation in hippocampal CA1 region in behaving rats. 本研究旨在探讨药物增强胆碱能输入对海马突触可塑性的影响。我们使用乙酰胆碱酯酶抑制剂物理斯亭对雄性大鼠海马长期增强（LTP）进行调节研究。结果显示，物理斯亭显著增强了海马LTP，表明增加乙酰胆碱水平可以特异性地增强动物的海马LTP。这一研究结果对治疗阿尔茨海默病等疾病具有重要意义。药物发现/临床前 SFN 2004 2004-10-27 水杨酸毒扁豆碱阿尔茨海默症 Univ Western Ontario Physostigmine enhances spontaneous alternation performance in diencephalic–lesioned rats. 本研究发现，丘脑损伤大鼠在自发交替测试中，海马乙酰胆碱释放显著减少，自发交替行为也减少。通过给予乙酰胆碱酯酶抑制剂物质菲索司亚胺，海马乙酰胆碱释放增加，自发交替行为得到改善。这一发现支持了调节乙酰胆碱水平对丘脑损伤大鼠学习和记忆表现的影响。药物发现/临床前 SFN 2003 2003-11-09 水杨酸毒扁豆碱 - Psychology, SUNY-Binghamton, Binghamton, NY Endogenous cholinergic neurotransmission in prebötzinger complex modulates excitability of inspiratory neurons and regulates respiratory pattern. 本研究发现，内源性胆碱能神经递质在前波茨氏复合体中调节吸气神经元的兴奋性并调节呼吸模式。实验结果表明，通过作用于M3型乙酰胆碱受体（mAChRs）和α4β2型尼古丁酸受体（nAChRs），胆碱能神经递质调节呼吸频率和模式。这一发现为胆碱能调节呼吸频率和模式的机制提供了新的认识。药物发现/临床前 SFN 2003 2003-11-09 水杨酸毒扁豆碱 - Dept. Neurobio, David Geffen Sch. Med. at UCLA, Los Angeles, CA Muscarinic receptor-mediated facilitation of epileptiform discharges in immature neocortex is augmented by gap junctions. 在这项研究中，我们发现乙酰胆碱能够增强幼年大鼠新皮层（出生后10-20天）癫痫样放电的发生率。这种效应主要通过肌动蛋白受体介导，特别是M1型受体。同时，我们也观察到缝隙连接的激活能够显著增强这种效应。这些发现为幼年大鼠新皮层癫痫样放电的调控机制提供了新的认识，也为相关疾病的治疗提供了新的思路。药物发现/临床前 SFN 2003 2003-11-09 水杨酸毒扁豆碱 - Ste. Justine Hosp. Res. Centre Cerebral Abeta deposition induced by cortical cholinergic deafferentation is reduced by cholinergic therapy. - 药物发现/临床前 SFN 2002 2002-11-06 NGX-267 | 水杨酸毒扁豆碱阿尔茨海默症 Sun Hlth Res Inst, Sun City, AZ ENDOGENOUS RELEASE OF ACETYLCHOLINE MODULATES THE LOCOMOTOR NETWORK OF THE LAMPREY SPINAL CORD. 本研究证明，乙酰胆碱（ACh）的内源释放对于对梭鱼脊髓的运动网络具有调节作用。实验结果显示，ACh酯酶抑制剂依西林的加入可显著减少游泳周期和相位滞后，而在依西林存在的情况下，植物碱受体拮抗剂和胆碱能受体拮抗剂的加入会进一步增加周期和相位滞后。这些实验结果表明，脊髓神经元释放的ACh足以对梭鱼的运动网络进行持续调节。这一研究得到了NIH NS35725 & NS40775的支持。药物发现/临床前 SFN 2002 2002-11-04 水杨酸毒扁豆碱 - Marquette University Physostigmine-Induced Revearsal of MK-801-Induced Spatial Memory Impairments But Not Fear Conditioning in Mice. 本研究旨在探究胆碱能药物对NMDA受体阻断引起的不同类型记忆缺陷的影响。实验结果表明，MK-801剂量依赖性地导致了逆转学习和环境-和提示依赖性条件反射的缺陷。而生物碱物质生理碱在剂量依赖性下显著改善了逆转学习的表现，但对环境依赖性条件反射的表现没有显著影响。这些结果表明，胆碱能药物能够克服NMDA受体阻断引起的空间记忆缺陷，但对条件反射缺陷的影响有限。这一发现提示，实验性诱导的空间记忆缺陷测试可能对已知对阿尔茨海默病患者具有认知增强作用的药物特别敏感。药物发现/临床前 SFN 2002 2002-11-03 水杨酸毒扁豆碱 - Dept Psychiatry Campus Box 8134, Washington Univ Sch Med, St Louis, MO TRANSGENIC ACHE EXERTS NON-CATALYTIC EFFECTS ON HIPPOCAMPAL LTP VIA PKC MODULATION. 本研究发现，AChE在海马LTP中发挥非催化作用，通过PKC调节。AChE-R过度表达增强LTP（172% vs. WT的138%），而AChE-S过度表达导致LTP迅速衰减至37%。PKC激活剂可显著促进AChE-R片段的突触场电位，但在AChE-S片段中效果不佳。此外，PKC激活后的短时强化可在AChE-S片段中诱导稳定的迟相LTP，从而挽救LTP的衰减。研究表明AChE的非催化特性通过PKC活性和/或水平参与LTP的启动和维持，可能展示了与压力相关的神经可塑性调节。药物发现/临床前 SFN 2002 2002-11-03 水杨酸毒扁豆碱 - The Hebrew University of Jerusalem RESIDUAL HIPPOCAMPAL CHOLINERGIC FUNCTIONS AFTER 192 IgG-SAPORIN LESIONS OF THE MEDIAL SEPTUM/VENTRAL DIAGONAL BAND (MS/VDB). - 药物发现/临床前 SFN 2002 2002-11-03 水杨酸毒扁豆碱 - Univ of IL at Urbana Champaign ENDOGENOUS ACETYLCHOLINE ACTING ON MUSCARINIC RECEPTORS ENHANCES EPILEPTIFORM DISCHARGES IN DISINHIBITED IMMATURE RAT NEOCORTEX. 在大鼠未成熟的新皮层中，内源性乙酰胆碱作用于肌碱受体增强了去抑制状态下的癫痫样放电。研究发现，抗胆碱酯酶剂使发作样和间发样自发放电频率显著增加，而使诱发场电位的幅度和持续时间减少。外源性胆碱能模拟这些效应，但其引起的自发放电频率增加明显高于抗胆碱酶剂。这些效应均能被肌碱受体拮抗剂阿托品阻断，而烟碱受体拮抗剂对这些效应没有影响。这些实验表明，内源性ACh通过肌碱受体增强了未成熟的去抑制新皮层的癫痫发生。该研究得到了NSERC、Savoy Foundation for Epilepsy、FRSQ (CP)、Ste Justine Hospital Research Center (SP)的支持。药物发现/临床前 SFN 2001 2001-11-14 水杨酸毒扁豆碱 epileptiform discharges University of Montreal Reversal of attentional dysfunction following AMPA lesions of the cholinergic basal forebrain by donepezil, physostigmine and by the 5-HT1A receptor antagonist WAY 100635. - 药物发现/临床前 SFN 2001 2001-11-14 水杨酸毒扁豆碱 | WAY-100635 | 盐酸多奈哌齐阿尔茨海默症 Mario Negri Institute | University of Milan Endogenous acetylcholine facilitates the generation of epileptiform discharges in immature rat neocortex. 本研究发现内源性乙酰胆碱有助于促进幼年大鼠新皮层中癫痫样放电的产生。研究结果显示，抗胆碱酯酶剂依西林通过抑制乙酰胆碱的降解，增加了内源性乙酰胆碱的浓度。在实验中，依西林显著增加了由双氯杆菌诱导的同步自发性放电的发生率，并且在一些情况下诱发了新的放电类型。此外，依西林还可逆地降低了诱发的场电位的幅度和持续时间。研究结果表明，内源性乙酰胆碱浓度的升高可能有助于促进幼年大鼠新皮层中癫痫样放电的产生，并可能通过降低单个放电的幅度和/或持续时间来预防长期兴奋性损伤。这些发现与之前在幼年海马中的研究结果相似。该研究得到NSERC和FRSQ的支持。药物发现/临床前 SFN 2000 2000-11-08 水杨酸毒扁豆碱 - Université de Montréal Cholinergic enhancement influences different cortical regions during working memory in young and older humans. 本研究探讨了乙酰胆碱增强对年轻和老年人工作记忆的影响。结果显示，乙酰胆碱增强剂对记忆表现有改善作用，并且在大脑记忆关键区域产生活动变化。年龄对大脑活动有影响，乙酰胆碱系统的增强对年轻和老年人的大脑反应不同。研究发现，乙酰胆碱增强剂降低了年轻和老年人的反应时间，但对大脑区域的影响不同，表明年轻和老年人的记忆网络招募方式不同。药物发现/临床前 SFN 2000 2000-11-08 水杨酸毒扁豆碱 - NIA | University of Pisa Acetylcholine mediates the estrogen-induced increase in hippocampal NMDA receptor binding and the associated enhancement in working memory performance. 雌激素引起的海马NMDA受体结合增加与工作记忆表现提高有关。研究发现，雌激素增加了海马CA1区脊柱和突触密度，与CA1金字塔细胞中NMDA结合增加有关。雌激素还增加了基底前脑和海马中胆碱能神经元的活性。研究推测，雌激素引起的胆碱能活性增加会促进M2胆碱能受体的活性，降低对金字塔细胞的抑制，从而增加其兴奋和NMDA结合。研究结果表明，乙酰胆碱（ACh）通过M2受体介导了雌激素引起的海马CA1区NMDA结合增加以及相关的工作记忆表现提高。药物发现/临床前 SFN 2000 2000-11-08 水杨酸毒扁豆碱 - Tulane Univ Physostigmine ameliorates impaired eyeblink classical conditioning in older rabbits. 研究发现，生物碱物质毒扁豆碱可以显著改善老年兔子眨眼经典条件反射的学习能力。研究表明，毒扁豆碱在一定剂量范围内可以显著提高老年兔子眨眼经典条件反射的学习表现，包括学习次数、条件反射百分比和反应延迟。这一改善可能是通过增强海马锥体神经元的兴奋性，从而影响了内侧颞叶回路的功能。这一研究结果对于了解毒扁豆碱在改善老年动物学习和记忆能力方面的作用具有重要意义。药物发现/临床前 SFN 2000 2000-11-08 水杨酸毒扁豆碱 - Albert Einstein Healthcare Network, Philadelphia, PA | Dept Psychol, Temple University, Philadelphia, PA Increasing acetylcholine levels in the hippocampus or the entorhinal cortex reverses avoidance deficits produced by septal GABA receptor stimulation. 本实验研究发现，增加海马或前视皮层中乙酰胆碱（ACh）水平可以逆转通过刺激乙酰胆碱受体的丘脑GABA受体产生的避免性缺陷。实验结果表明，通过海马或前视皮层内注射乙酰胆碱酯酶抑制剂physostigmine可以完全逆转GABA受体激动剂muscimol的记忆损害效应。这些结果支持了丘脑GABA能系统通过下调海马和前视皮层中ACh水平来损害记忆的假设。药物发现/临床前 SFN 2000 2000-11-07 水杨酸毒扁豆碱 - Division of Neuroscience, University of Alberta, Edmonton, Canada Effects of physostigmine on cocaine-induced behavior in rats. 本研究探讨了乙酰胆碱酯酶抑制剂毒扁豆碱对亚急性可卡因处理大鼠行为的影响。结果显示，连续5天用可卡因处理的大鼠对毒扁豆碱的挑战表现出增强的行为反应，而用毒扁豆碱和可卡因联合处理的大鼠在可卡因挑战后表现出嗅探行为的增加。这些结果暗示乙酰胆碱在敏感化过程中的参与，并且在NAC和STR区域发生了差异。这一研究结果对于了解精神刺激物诱导的精神病和药物成瘾具有重要意义。药物发现/临床前 SFN 2000 2000-11-07 水杨酸毒扁豆碱 - University of Cagliari | University Tuebingen | Claude Bernard Neuroscience Institute Input-specific effects of acetylcholine on sensory and intracortical evoked responses in the barrel cortex in vivo. 本研究探讨了乙酰胆碱对大鼠须桶皮层感觉和皮层内诱发反应的输入特异性影响。结果显示，乙酰胆碱在皮层内抑制了诱发反应，但对感觉诱发反应的影响则呈剂量依赖性。胆碱能激动剂马斯卡林抑制了皮层内和感觉诱发反应，而尼古丁或尼古丁能激动剂DMPP增强了感觉反应，对皮层内反应影响较小。此外，增加乙酰胆碱的内源水平也呈现出类似的效应。研究结果表明，乙酰胆碱对大鼠须桶皮层的感觉和皮层内反应具有不同的调节作用。该研究得到了MRC、NSERC、CFI、FRSQ和Savoy Foundation的支持。药物发现/临床前 SFN 2000 2000-11-05 水杨酸毒扁豆碱 - Neurology and Neurosurgery, Montreal Neurological Institute, Montreal, Canada Physostigmine potentiates α4β4 nAChRs by a competitive mechanism. Physostigmine通过竞争机制增强了α4β4 nAChRs的作用。研究表明，Physostigmine和相关的胆碱酯酶抑制剂（AChEIs）能够激活单个nAChR通道，并增强激动剂诱导的整细胞电流。但是，Physostigmine的增强效应是通过与nAChRs的竞争性相互作用而实现的。根据浓度效应曲线显示，低浓度的Physostigmine能够增强离子电流，而高浓度则会抑制由低浓度激动剂诱导的离子电流。这表明Physostigmine是α4β4 nAChR的竞争性共激动剂。通过放射配体结合实验证实了Physostigmine与α4β4 nAChRs的竞争性相互作用。该研究结果为后续生物医药领域的实验研究提供了重要参考依据。#903.42.066 N.W.O.的支持。药物发现/临床前 SFN 2000 2000-11-05 水杨酸毒扁豆碱 - Eli Lilly & Co. | RITOX, Utrecht Univ, Utrecht, The Netherlands Effects of N-methyl-d-aspartate antagonists and acetylcholinesterase inhibitors: fluoro-jade staining, behavior, and photodiode array imaging. - 药物发现/临床前 SFN 2000 2000-11-05 Dizocilpine | 水杨酸毒扁豆碱 | 溴吡斯的明 - VA Neurol, Research & Duke Depts. Pharmacol. & Cancer, Biol. & Neurosurg. Veterans Admin. Med Cntr., Durham, NC

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适应症	最高研发状态	国家/地区	公司	日期
继发性干燥综合征	临床2期	美国	TorreyPines Therapeutics, Inc.	2008-02-01
失盐型肾上腺皮质综合症	临床2期	美国	TorreyPines Therapeutics, Inc.	2008-02-01
阿尔茨海默症	临床2期	-	Raptor Pharmaceutical, Inc.	-
认知障碍	临床2期	-	Raptor Pharmaceutical, Inc.	-