Novel Off-label Use of Desipramine in Infantile Neuroaxonal Dystrophy: Targeting the Sphingolipid Metabolism Pathway to Reduce Accumulation of Ceramide.

This is a research study to find out if clinically prescribed desipramine is effective at improving the symptoms and slowing the progression of Infantile Neuroaxonal Dystrophy (INAD) in affected children.
Participants will receive an initial oral dose of study drug once a day. This dose may be changed depending on response to study drug Clinically collected data will be recorded for up to 5 years. Investigators will also ask for participant permission to obtain a sample of child's skin biopsy from unused clinical sample previously collected for standard of care.

开始日期2019-01-14

申办/合作机构

Duke University

NCT03548454 / Recruiting临床4期IIT

Comparing Effectiveness of Duloxetine and Desipramine in Patients With Chronic Pain: A Pragmatic Trial Using Point of Care Randomization

Over 100 million Americans suffer from chronic pain resulting in annual cost of roughly $635 billion. Limited treatments are available for this widespread disease. The data supporting these treatments lack generalizability to patients with more serious medical and psychological comorbidities who are often excluded from explanatory efficacy trials. Our work aims to integrate randomized comparative effectiveness research with patient care. The investigators will randomize the patients and collect data using an open-source learning healthcare system already in use in our department to monitor patients' progress: Collaborative Health Outcomes Information Registry (CHOIR). Collaborative Health Outcomes Information Registry uses the National Institute of Health Patient Reported Outcomes Measurement Information System item banks for comparative metrics through computer adaptive testing. The investigators will leverage the advantage of this novel system to compare effectiveness of duloxetine and desipramine in decreasing pain in patients with chronic pain. The investigators will also compare adherence of patients to these two commonly used medications over a period of six months. This will evaluate feasibility of integrating randomized comparative effectiveness research with patient care in subspecialty clinics. Collaborative Health Outcomes Information Registry can then be applied for numerous future trials to advance our knowledge in perioperative and pain medicine.

开始日期2018-09-20

申办/合作机构

Stanford University

IRCT20160813029315N2 / Completed临床2/3期IIT

Placebo-controlled randomized clinical trial testing the efficacy of desipramine in reducing craving in patients with methamphetamine use disorder

开始日期2016-06-03

申办/合作机构-

100 项与盐酸地昔帕明相关的临床结果

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100 项与盐酸地昔帕明相关的转化医学

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100 项与盐酸地昔帕明相关的专利（医药）

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项与盐酸地昔帕明相关的文献（医药）

2024-04-01·Pest management science

Workflows for detecting fungicide resistance in net form and spot form net blotch pathogens

Article

作者: Knight, Noel L ; Mair, Wesley J ; Dodhia, Kejal N ; Lopez-Ruiz, Francisco J ; Adhikari, Kul C

Abstract:

BACKGROUND:

Fungicide resistance in Pyrenophora teres f. maculata and P. teres f. teres has become an important disease management issue. Control of the associated barley foliar diseases, spot form and net form net blotch, respectively, relies on three major groups of fungicides, demethylation inhibitors (DMIs), succinate dehydrogenase inhibitors (SDHIs) and quinone outside inhibitors (QoIs). However, resistance has been reported for the DMI and SDHI fungicides in Australia. To enhance detection of different resistance levels, phenotyping and genotyping workflows were designed.

RESULTS:

The phenotyping workflow generated cultures directly from lesions and compared growth on discriminatory doses of tebuconazole (DMI) and fluxapyroxad (SDHI). Genotyping real‐time polymerase chain reaction (PCR) assays were based on alleles associated with sensitivity or resistance to the DMI and SDHI fungicides. These workflows were applied to spot form and net form net blotch collections from 2019 consisting predominantly of P. teres f. teres from South Australia and P. teres f. maculata from Western Australia. For South Australia the Cyp51A L489‐3 and SdhC‐R134 alleles, associated with resistance to tebuconazole and fluxapyroxad, respectively, were the most prevalent. These alleles were frequently found in single isolates with dual resistance. This study also reports the first detection of a 134 base pair insertion located at position‐66 (PtTi‐6) in the Cyp51A promoter of P. teres f. maculata from South Australia. For Western Australia, the PtTi‐1 insertion was the most common allele associated with resistance to tebuconazole.

CONCLUSION:

The workflow and PCR assays designed in this study have been demonstrated to efficiently screen P. teres collections for both phenotypic and genetic resistance to DMI and SDHI fungicides. The distribution of reduced sensitivity and resistance to DMI and SDHI fungicides varied between regions in south‐western Australia, suggesting the emergence of resistance was impacted by both local pathogen populations and disease management programmes. The knowledge of fungicide resistance in regional P. teres collections will be important for informing appropriate management strategies. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

2024-03-01·The European journal of neuroscience

Transporters involved in adult rat cortical astrocyte dopamine uptake: Kinetics, expression and pharmacological modulation

Article

作者: Sočan, Vesna ; Dolinar, Klemen ; Kržan, Mojca

Abstract:

Astrocytes, glial cells in the central nervous system, perform a multitude of homeostatic functions and are in constant bidirectional communication with neuronal cells, a concept named the tripartite synapse; however, their role in the dopamine homeostasis remains unexplored. The aim of this study was to clarify the pharmacological and molecular characteristics of dopamine transport in cultured cortical astrocytes of adult rats. In addition, we were interested in the expression of mRNA of dopamine transporters as well as dopamine receptors D1 and D2 and in the effect of dopaminergic drugs on the expression of these transporters and receptors. We have found that astrocytes possess both Na+‐dependent and Na+‐independent transporters. Uptake of radiolabelled dopamine was time‐, temperature‐ and concentration‐dependent and was inhibited by decynium‐22, a plasma membrane monoamine transporter inhibitor, tricyclic antidepressants desipramine and nortriptyline, both inhibitors of the norepinephrine transporter. Results of transporter mRNA expression indicate that the main transporters involved in cortical astrocyte dopamine uptake are the norepinephrine transporter and plasma membrane monoamine transporter. Both dopamine receptor subtypes were identified in cortical astrocyte cultures. Twenty‐four‐hour treatment of astrocyte cultures with apomorphine, a D1/D2 agonist, induced upregulation of D1 receptor, norepinephrine transporter and plasma membrane monoamine transporter, whereas the latter was downregulated by haloperidol and L‐DOPA. Astrocytes take up dopamine by multiple transporters and express dopamine receptors, which are sensitive to dopaminergic drugs. The findings of this study could open a promising area of research for the fine‐tuning of existing therapeutic strategies.

2024-03-01·Neuropsychopharmacology reports

Neuron‐specific deletion of VEGF or its receptor Flk‐1 occludes the antidepressant‐like effects of desipramine and fluoxetine in mice

Article

作者: Deyama, Satoshi ; Duman, Ronald S ; Li, Xiao-Yuan

Abstract:

Vascular endothelial growth factor (VEGF) signaling is known to be involved in the antidepressant‐like effects of conventional antidepressants, such as desipramine (DMI), a tricyclic antidepressant, and fluoxetine (FLX), a selective serotonin reuptake inhibitor; however, the precise role of neuronal VEGF signaling in mediating these effects remains unclear. Using mice with excitatory neuron‐specific deletion of VEGF and its receptor, fetal liver kinase 1 (Flk‐1) in the forebrain, we examined the effects of forebrain excitatory neuron‐specific deletion of VEGF or Flk‐1 on the antidepressant‐like effects of repeated DMI and chronic FLX administration in the forced swim test (FST). Repeated intraperitoneal (i.p.) injections of DMI (10, 10, and 20 mg/kg at 24, 4, and 1 h before the FST, respectively) significantly decreased immobility in control mice; however, this effect was completely blocked in mice with neuron‐specific VEGF or Flk‐1 deletion. Although chronic treatment with FLX (18 mg/kg/day, i.p.) did not impact immobility in control mice 1 day after the 22nd injection, immobility was significantly reduced 1 day after the preswim and the 23rd FLX injection. However, in mice with neuron‐specific Flk‐1 deletion, chronic FLX treatment significantly increased immobility in the preswim and failed to produce antidepressant‐like effects. Collectively, these findings indicate that neuronal VEGF–Flk‐1 signaling contributes to the antidepressant‐like actions of conventional antidepressants.

项与盐酸地昔帕明相关的新闻（医药）

2024-05-06

·BioSpace

Boehringer Ingelheim shares positive results from the first study worldwide in diabetic macular ischemia

Boehringer Ingelheim today presented positive data from the HORNBILL Phase I/IIa study of BI 764524, the first ever study exploring a potential treatment for people living with diabetic macular ischemia (DMI). The study found that BI 764524 was well tolerated following intravitreal administration of single and multiple doses, meeting its primary safety endpoints and showed early signs of potential efficacy.1 DMI is a common, irreversible complication of diabetic retinopathy (DR) that may lead to blindness.12,3,4 It can develop when the light sensitive tissues of the central retina do not receive adequate blood supply over a longer time. There are currently no approved treatments for DMI. The current standard of care for advanced DR includes intravitreal anti-VEGF treatment or invasive laser treatment. However, some patients’ conditions progress despite this treatment.5 BI 764524 uses a novel mode of action by inhibiting the Sema3A pathway to re-vascularize ischemic areas and potentially overcome the limitations of anti-VEGF and laser treatments.1 “The results from the HORNBILL study are really encouraging. They suggest there may be a pathway for earlier intervention that could decrease the risk of, and maybe even prevent, people with diabetic retinopathy from developing irreversible and vision-threatening complications, such as DMI,” said Quan Dong Nguyen, MD, MSc, FARVO, FASRS, Professor of Ophthalmology at the Byers Eye Institute, Professor of Medicine and of Pediatrics at Stanford School of Medicine, and Principal and Coordinating Investigator of the trial. “Retinal non-perfusion is a key driver of vision loss in people living with diabetic retinopathy. However, until the HORNBILL study, retinal non-perfusion has not been explored as a potential treatment target.” “Vision loss associated with retinal conditions such as diabetic retinopathy and DMI has a devastating impact on quality of life. Today’s results are an important step towards achieving our aspiration of developing precision therapies delivering the right treatment for the right patient at the right time to prevent vision loss before irreversible damage occurs,” said Ulrike Graefe-Mody, Ph.D., Head of Retinal Health at Boehringer Ingelheim. “We’re looking forward to start a Phase IIb study to further explore the safety and efficacy of BI 764524.” HORNBILL is one of 23 abstracts being presented at the Association for Research in Vision and Ophthalmology (ARVO) Annual meeting 2024, spanning Boehringer Ingelheim’s retinal health portfolio, including other studies of retinal non-perfusion and diabetic retinopathy, geographic atrophy and neovascular age-related macular degeneration. About the HORNBILL study The HORNBILL study consisted of two parts (single rising dose (SRD), N=12 and multiple dose (MD), N=31) both of which met the primary safety endpoints of number of patients with dose-limiting adverse events (SRD) and treatment-related adverse events(MD).1 The study also met its pre-specified criterion for early efficacy of foveal avascular zone area stabilization versus sham at week 16 (p<0.2).1 This suggests that BI 764524 may positively impact retinal non-perfusion and potentially halt the progression of capillary loss.1 The upcoming CRIMSON trial, a Phase IIb trial, will assess safety and efficacy of BI 764524 in patients with DR further and start recruiting later this year. Notes to Editors: About the trial (NCT04424290) This Phase I/IIa trial assessed the tolerability of BI 764524 in people with diabetic retinopathy (DR) with diabetic macular ischemia (DMI) who have previously been treated with panretinal photocoagulation.1 The trial consisted of a single rising dose (SRD) part followed by a multiple dosing (MD) part, with BI 764524 administered via intravitreal injection.1 Single rising dose part In the non-randomized, open-label, SRD part, 12 patients received intravitreal BI 764524 doses: 0.5 (n=3), 1.0 (n=3), or 2.5 mg (n=6).1 The primary endpoint was the number of patients with dose-limiting events (DLEs); secondary endpoints were the number of patients with drug-related adverse events (AEs) and any ocular AEs.1 Patients in the SRD part had a mean age of 61.8 years.1 No DLEs were reported in the SRD part.1 There were five ocular AEs in four patients in the study eye, none related to the study drug. The highest tested dose (BI 764524 2.5 mg) was considered safe and applied in the MD part.1 Multiple dosing part In the randomized, masked, sham-controlled, MD part, 31 patients received three intravitreal doses of BI 764524 2.5 mg (n=21) or sham injection procedures (n=10) at 4-week intervals (baseline, week 4, and week 8), followed by 14 weeks of follow-up until the end of study at week 22.1 The primary endpoint was the number of patients with drug-related AEs; secondary endpoints included number of patients with ocular AEs, change from baseline in foveal avascular zone (FAZ) area, best corrected visual acuity (BCVA) and central retinal thickness (CRT).1 Patients in the MD part had a mean age of 59.5 years.1 There were seven patients with ocular AEs (study eye; three patients with four AEs for BI 764524, four patients with six AEs for sham), one of which was reported as related to the study drug (vitreous floater).1 In addition, there was one systemic AE (increase deemed related to the study drug by the investigator). There were no cases of intraocular inflammation or occlusive retinal vasculitis.1 At baseline, mean BCVA was 65.2 letters, mean FAZ area was 0.65 mm, and mean CRT was 252 mm.1 The HORNBILL study met its pre-specified criterion for early efficacy of FAZ area stabilization versus sham at week 16 (p<0.2). Over the short trial period, other secondary efficacy endpoints showed no relevant change. About BI 764524 BI 764524 is a humanized monoclonal anti-Sema3A antibody intended to re-vascularize ischemic areas and reduce leakage in the retina, offering the potential to address retinal non-perfusion in retinal diseases. The compound was discovered and developed by Boehringer Ingelheim and is part of its research and development portfolio in retinal conditions. About diabetic retinopathy and diabetic macular ischemia Diabetic retinopathy affects 1 in 3 people with diabetes and is the leading cause of vision loss in adults of working age. It is a growing epidemic that is expected to increase as the incidence of diabetes escalates across the globe. Diabetic macular ischemia (DMI) is a complication of diabetic retinopathy which can lead to slowly progressing, irreversible vision loss. About Boehringer Ingelheim Boehringer Ingelheim is working on breakthrough therapies that transform lives, today and for generations to come. As a leading research-driven biopharmaceutical company, the company creates value through innovation in areas of high unmet medical need. Founded in 1885 and family-owned ever since, Boehringer Ingelheim takes a long-term, sustainable perspective. More than 53,000 employees serve over 130 markets in the two business units Human Pharma and Animal Health. Learn more at Boehringer Ingelheim’s Intended Audiences Notice This press release is issued from our Corporate Headquarters in Ingelheim, Germany and is intended to provide information about our global business. Please be aware that information relating to the approval status and labels of approved products may vary from country to country, and a country-specific press release on this topic may have been issued in the countries where we do business. References 1 Nguyen QD, Jhaveri C, Habib MS. Oral presentation at the Association for Research in Vision and Ophthalmology (ARVO) 2024. Abstract number: 959 2 Marques IP, et al. Diabetes 2019;68:648–653 3 Sim DA, et al. Invest Ophthalmol Vis Sci 2013;54:2353–2360 4 Tey KY, et al. Eye Vis (Lond) 2019;6:37 5 Ip MS, et al. Ophthalmology 2014;122:367–374

临床结果临床2期

2023-11-28

·药研网

探寻抑郁症新型可行性靶点

2023年8月，Sage治疗产后抑郁的药物Zurzuvae获FDA批准上市，成为FDA批准的首款专门用于产后抑郁的口服药；继而2023年9月，Fabre-Kramer治疗重度抑郁的药物Exxua获FDA批准上市，历时20年，被FDA拒绝三次，终于在第四次申请时获批上市。重度抑郁症是全世界非常普遍的疾病之一，且抑郁症的发展越来越趋于年轻化，青少年患抑郁症的比例不断升高。青少年患重度抑郁更为棘手，因为其将面临一生的负面影响。据《2022年国民抑郁症蓝皮书》显示，国内50%的抑郁症患者为在校学生，18岁以下的抑郁症患者占总人数的30%。有研究认为，成年期抑郁症在青少年时期已发病。目前青少年治疗抑郁的首选药物是氟西汀，但也有一些显著的副作用，如增加自杀意念。而成年的抗抑郁药以选择性5-HT再摄取抑制剂（SSRIs）为主，包括氟西汀、帕罗西汀、舍曲林、氟伏沙明、西酞普兰、艾司西酞普兰，但大约 35-50% 的患者对这些药物没有反应，且通常具有嗜睡、镇静和性功能障碍等常见不良反应。近几年，也有一些新机制抗抑郁药获批，如NMDA受体拮抗剂Spravato，GABAA受体正向变构调节剂Zulresso。但其仅获批用于部分适应症，如Spravato 仅适用于耐药性抑郁症，Zulresso仅用于产后抑郁症。因此，需要寻找更安全，新机制的药物靶点，开发疗效更佳的新型抗抑郁药物。神经可塑性作为抗抑郁机制在重度抑郁患者中，前额叶皮层（PFC）和海马体体积缩小是大脑解剖学上的一致发现，前额叶皮层的突触数量也有所减少。这一事实表明，神经可塑性是 MDD 生理病理学中一个基本而关键的现象。动物和临床研究表明，慢性压力是 MDD 的病因，它会导致 PFC 和海马突触的数量和功能下降。SSRIs 可增加抑郁症患者血清和大鼠海马中脑源性神经营养因子（BDNF）的表达，而 BDNF 是新突触形成所必需的。只有在对大鼠长期（两周以上）而非急性服用 SSRIs 后，BDNF 才会增加，这表明 BDNF 以及神经可塑性参与了在行为中观察到的抗抑郁效果。Specific targets related to the modulation of synaptic plasticity and energetic metabolism. 以新兴神经递质系统为目标除了血清素和谷氨酸外，GABAergic和cholinergic两种神经递质系统也被认为是治疗 MDD 的有效药物。磁共振波谱（MRS）研究证实，抑郁症患者脑脊液（CSF）中的 GABA 含量降低。在有效治疗 MDD 后，GABA 水平也会恢复正常。动物研究显示，慢性压力会诱导啮齿动物GABA合成酶的表达以及 GABA 的释放和摄取减少。此外，GABAA 表达减少的小鼠会出现类似抑郁症的表型，长期服用地西帕明可以改善这种情况。在使用cholinergic拮抗剂 scopolamine进行临床前研究期间，观察到了抗抑郁效果，在动物模型中也观察到了scopolamine的突触生成和激活mTOR信号转导的作用，这些效应暗示了乙酰胆碱在多发性抑郁症中的作用。但也有研究显示安慰剂组和scopolamine组在抗抑郁方面无显著差异。因此目前关于cholinergic系统作为抗抑郁靶点的潜力，目前尚无定论。褪黑素在使用 5-10 mg褪黑素的随机研究中，与安慰剂相比，双相情感障碍和单相情感障碍患者在服用褪黑素后都没有观察到显著的抗抑郁效果。同时，Fava 等人在一项双盲研究中表明，丁螺环酮与 3mg褪黑素联合使用比丁螺环酮与安慰剂联合使用更有效。Lewy等人的研究表明，当根据时间型调整给药剂量时，褪黑激素对季节性情感障碍的抗抑郁作用更大从目前的研究来看，褪黑素可能成为抗抑郁治疗的有效辅助药物，而非主要治疗手段。神经炎症：色氨酸-犬尿氨酸途径神经炎症与多种神经系统疾病有关，炎症和细胞介导的免疫激活是抑郁症的关键因素。动物模型显示，暴露于脂多糖可诱发抑郁样行为。此外，人体研究和荟萃分析表明，抑郁症患者血液和脑脊液中的外周促炎标志物水平升高。与此相对应，耐药性 MDD 患者的促炎细胞因子继续增加。这证实了促炎细胞因子水平与抑郁症严重程度之间的正相关性。The tryptophan – kynurenic acid metabolic pathway and major depressive disorder. 对用于治疗 MDD 的抗炎药物进行的 Meta 分析表明，非甾体类抗炎药物（NSAIDs）的单一疗法或作为辅助疗法的使用可改善抑郁症状，且缓解率较高。然而，尽管大多数非甾体抗炎药抑制环氧化酶（COX），但人们对其在抑郁症中的作用持怀疑态度。能量代谢、线粒体2 型糖尿病（DM）、肥胖症和肌肉疏松症等几种新陈代谢疾病与抑郁症发病几率增加有关。鉴于新陈代谢紊乱、氧化应激和神经炎症与抑郁症的关系，对作用于新陈代谢的药物进行了测试，结果发现这些药物具有抗抑郁作用。据报道，对于患有心脏代谢紊乱的患者，抗糖尿病药物可减轻抑郁症状。线粒体功能障碍是代谢性疾病的典型症状。多发性抑郁症患者的线粒体活性以及一系列线粒体蛋白的表达都会下降，他们的神经元代谢也会出现缺陷。抗抑郁治疗可改善这种代谢缺陷。线粒体基因突变也与抑郁症有关。因此，新陈代谢和线粒体功能可能是改变 MDD 病理生理学的重要部位。与线粒体功能相关的三个潜在靶点包括Complex I、NAD 和 CoQ 10。与代谢相关的潜在靶点包括二甲双弧，GLP-1。The gut–brain axis as a target微生物组近年来，由于人们对肠道微生物群如何影响大脑功能的认识上取得了最新进展，"肠脑轴"在生物医学研究中备受关注。研究表明，多发性抑郁症患者的肠道微生物组发生了改变，细菌多样性减少。在小鼠体内，一些细菌及其代谢产物能够增加抑郁样行为的易感性，并阻碍某些药物的抗抑郁效果。相反，其他代谢物则能改善小鼠的认知能力和情绪。一项动物研究表明，将 MDD 患者的粪便移植到非生物小鼠体内会导致抑郁症状的出现，如失乐症和焦虑样行为，以及 TRY 代谢的改变。一项临床研究表明，有八种不同细菌菌株的益生菌混合物具有抗抑郁作用，而乳酸菌数量的增加推动了这种作用。但尽管调整肠道微生物组具有成本效益和实用性等优势，但由于组成肠道微生物组的微生物物种数量庞大，确定哪些细菌群可能影响行为改变具有挑战性。此外，还需要确定微生物组影响大脑的机制，以便更准确地了解潜在的目标。肠道微生物组及其代谢物可被视为开发抗抑郁药物的良好候选物，但还需要进一步的临床证据。细胞系产品查询投稿丨商务合作转载丨加交流群往期推荐恒瑞医药生物药管线全梳理中生制药企业梳理石药集团生物药技术平台及管线梳理国内ADC热门靶点竞争格局一览点击下方“药研网”，关注更多精彩内容

上市批准临床研究

2023-11-22

·PRNewswire

Novel MRI Reveals Brain Changes in Long-COVID Patients

CHICAGO, Nov. 22, 2023 /PRNewswire/ -- People with long COVID exhibit patterns of changes in the brain that are different from fully recovered COVID-19 patients, according to research being presented next week at the annual meeting of the Radiological Society of North America (RSNA). "To the best of our knowledge, this is the first study comparing patients with long COVID to both a group without history of COVID-19 and a group that went through a COVID-19 infection but is subjectively unimpaired," said one of the study's lead authors, Alexander Rau, M.D., resident in the Departments of Neuroradiology and Diagnostic and Interventional Radiology at University Hospital Freiburg in Freiburg, Germany. After infection with COVID-19, as many as 10-25% of patients may develop a post-COVID condition commonly referred to as "long COVID." People with long COVID may experience a wide variety of symptoms, including difficulty concentrating ("brain fog"), change in sense of smell or taste, fatigue, joint or muscle pain, shortness of breath, digestive symptoms, and more. These symptoms may persist for weeks, months, or—as is only now becoming apparent—years after COVID-19 infection. However, the basis of this condition is poorly understood. Diffusion microstructure imaging (DMI), a novel MRI technique, is a promising approach to fill this gap. DMI looks at the movement of water molecules in tissues. By studying how water molecules move in different directions and at various speeds, DMI can provide detailed information on the microstructure of the brain. It can detect even very small changes in the brain, not detectable with conventional MRI. For this prospective, cross-sectional study, Dr. Rau and colleagues compared MRI brain scans of three groups: 89 patients with long COVID, 38 patients that had contracted COVID-19 but did not report any subjective long-term symptoms, and 46 healthy controls with no history of COVID-19. The researchers first compared the cerebral macrostructure of these three groups to test for atrophy or any other abnormalities. Next, they used DMI to gain a deeper insight into the brain. The three groups were compared to reveal group differences in the brain's microstructure. DMI parameters were read for the gray matter in the brain. Additionally, whole brain analyses were employed to reveal the spatial distribution of alterations and associations with clinical data, including long-COVID symptoms like fatigue, cognitive impairment or impaired sense of smell. The results showed no brain volume loss or any other lesions that might explain the symptoms of long COVID. However, COVID-19 infection induced a specific pattern of microstructural changes in various brain regions, and this pattern differed between those who had long COVID and those who did not. "This study allows for an in vivo insight on the impact of COVID-19 on the brain," Dr. Rau said. "Here, we noted gray matter alterations in both patients with long-COVID and those unimpaired after a COVID-19 infection. Interestingly, we not only noted widespread microstructural alterations in patients with long COVID, but also in those unimpaired after having contracted COVID-19." The findings also revealed a correlation between microstructural changes and symptom-specific brain networks associated with impaired cognition, sense of smell and fatigue. "Expression of post-COVID symptoms was associated with specific affected cerebral networks, suggesting a pathophysiological basis of this syndrome" Dr. Rau said. The researchers hope to reexamine the patients in the future, recording both clinical symptoms and changes to the brain's microstructure. Despite these brain imaging findings, it remains unclear why some people develop long COVID while others do not, although previous studies have identified risk factors including female sex, older age, higher body mass index, smoking, preexisting comorbidities, and previous hospitalization or intensive care unit admission. Co-authors are Jonas A. Hosp, M.D., Nils Schroter, M.D., Marco Reisert, Ph.D., Horst Urbach, M.D., Cornelius Weiller, M.D., and Elias Kellner, Ph.D. Note: Copies of RSNA 2023 news releases and electronic images will be available online at RSNA.org/press23. RSNA is an association of radiologists, radiation oncologists, medical physicists and related scientists promoting excellence in patient care and health care delivery through education, research and technologic innovation. The Society is based in Oak Brook, Illinois. (RSNA.org) Editor's note: The data in these releases may differ from those in the published abstract and those actually presented at the meeting, as researchers continue to update their data right up until the meeting. To ensure you are using the most up-to-date information, please call the RSNA Newsroom at 1-312-791-6610. For patient-friendly information on brain MRI, visit RadiologyInfo.org. SOURCE Radiological Society of North America (RSNA)

临床结果

100 项与盐酸地昔帕明相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D00812	盐酸地昔帕明	N06AA01	DB01151

研发状态

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
抑郁症	美国	Validus Pharmaceuticals LLC	1964-11-20

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临床结果

适应症

分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01899326 (CTgov)	N/A	浆细胞骨髓瘤难治	10	Laboratory Biomarker Analysis+Filgrastim+Desipramine Hydrochloride	窪願醖齋餘夢襯鹹淵夢(顧獵鹹膚醖簾艱衊壓製) = 構餘遞觸繭廠範構鹹獵鏇夢醖艱鏇鹹餘選鑰觸 (獵顧觸餘鏇簾夢觸築選, 餘範鹽憲衊願遞壓構糧 ~ 築構憲蓋鹽襯獵壓範膚) 更多	-	2023-03-28
ISTH2021	N/A	-	-	Desipramine	構衊築廠鬱憲積選鏇遞(願艱鹹醖簾選簾廠鏇鹽) = 糧鹽壓簾醖廠蓋製糧淵廠顧網鏇獵醖鑰壓膚壓 (選築夢鹽淵觸壓鏇膚糧 )	-	2021-07-17
				PRP pre-incubated with 10μM desipramine	構衊築廠鬱憲積選鏇遞(願艱鹹醖簾選簾廠鏇鹽) = 獵糧鑰繭願築鏇築鏇壓廠顧網鏇獵醖鑰壓膚壓 (選築夢鹽淵觸壓鏇膚糧 )
NCT03726996 (CTgov)	临床4期	神经轴索营养不良	4	Desipramine	積醖鑰繭鬱淵獵鹽鏇餘(築繭製艱憲鹹醖築遞簾) = 遞鏇繭窪窪築鹹壓網憲遞獵糧艱衊廠網壓繭遞 (鹹壓願蓋獵壓襯願鹹襯, 願願齋蓋醖積鬱構鑰廠 ~ 艱襯蓋艱鏇醖鬱築艱築) 更多	-	2020-10-14
NCT01411085 (CTgov)	临床2期	酗酒 \| 精神分裂症	12	Risperidone+Desipramine	膚鬱鹹選襯觸壓壓襯糧(襯淵繭壓積鹽製襯繭鏇) = 淵鏇獵製網壓鬱衊齋觸願鹹艱鏇壓憲簾餘衊糧 (選鬱膚窪膚觸製鹹廠鏇, 齋鏇願鏇鑰艱構觸壓鏇 ~ 蓋築鏇簾鹹網艱繭衊鹹) 更多	-	2018-03-23
NCT00990691 (Pubmed \| Ann Clin Transl Neurol)	临床2期	Rett综合征	36	high Desipramine	衊窪糧壓網憲鹹製觸簾(鹹憲糧觸鬱鹽鬱獵繭選) = 鑰壓襯製鹹築壓觸願繭獵夢憲鹽襯觸鹹鏇壓糧 (襯積憲衊願簾齋鏇範鹽, -37 ~ -11)	不佳	2018-02-01
				low Desipramine	衊窪糧壓網憲鹹製觸簾(鹹憲糧觸鬱鹽鬱獵繭選) = 鑰鑰壓齋艱獵鏇鹹繭鬱獵夢憲鹽襯觸鹹鏇壓糧 (襯積憲衊願簾齋鏇範鹽, -31 ~ 13)
NCT00338962 (CTgov)	临床3期	酗酒 \| 抑郁症 \| 创伤后应激障碍 ... 更多	88	paroxetine+Naltrexone (Paroxetine and Naltrexone)	遞鏇構憲選繭積鏇鏇廠(壓製夢鹹網齋築繭願顧) = 襯醖鹹簾構願製壓齋膚築選鏇鏇糧繭鹽鏇膚艱 (獵網簾構蓋膚積簾積窪, 選築鹹選鹽鏇襯憲觸網 ~ 簾築鏇鏇鑰遞鏇願網簾) 更多	-	2016-02-05
				Placebo+paroxetine (Paroxetine and Placebo)	遞鏇構憲選繭積鏇鏇廠(壓製夢鹹網齋築繭願顧) = 願壓網鬱醖糧築糧願選築選鏇鏇糧繭鹽鏇膚艱 (獵網簾構蓋膚積簾積窪, 鑰觸獵齋襯夢繭艱選繭 ~ 遞繭襯鹽齋窪積構壓餘) 更多
NCT00166114 (CTgov)	临床4期	重度抑郁症 \| 抑郁	40	Escitalopram (Escitalopram)	簾憲壓獵範鹽繭鏇夢選(膚構齋鏇獵觸淵顧壓憲) = 選鏇鑰鏇夢選襯糧鏇廠積願鬱鹹鹹餘鏇廠繭獵 (鏇網壓構鬱憲艱築壓鬱, 餘齋餘網餘鏇獵鏇獵壓 ~ 糧遞鹽廠築糧繭製鬱築) 更多	-	2015-07-23
				Desipramine (Desipramine)	簾憲壓獵範鹽繭鏇夢選(膚構齋鏇獵觸淵顧壓憲) = 鏇鬱窪鏇窪構築餘餘鬱積願鬱鹹鹹餘鏇廠繭獵 (鏇網壓構鬱憲艱築壓鬱, 糧鹹繭齋範廠鑰構遞觸 ~ 襯鏇願顧鏇齋鏇遞獵構) 更多
NCT00000271 (Pubmed \| Drug Alcohol Depend)	临床2期	抑郁症	111	Desipramine	餘鹽廠積顧淵壓範艱齋(淵壓繭網簾蓋鹽顧繭積) = 觸淵夢網顧積窪築遞廠顧積糧蓋遞窪糧鑰鹽襯 (獵遞繭製網築衊選繭鑰 )	-	2005-11-01
				Placebo	餘鹽廠積顧淵壓範艱齋(淵壓繭網簾蓋鹽顧繭積) = 觸願鏇範壓淵鹽範繭觸顧積糧蓋遞窪糧鑰鹽襯 (獵遞繭製網築衊選繭鑰 )