One-third of the patients with major depressive disorder do not respond to conventional antidepressants that act through the mono-aminergic system. The available treatment modalities, including SSRIs, are slow to act and have a lag time before showing improvement in symptoms of patients. To overcome these treatment hurdles, add-on therapy to standard antidepressant drugs may lead to better therapeutic outcomes. Sarcosine, which is a nutraceutical, modulates glutamate neurotransmission has an ameliorative effect on the disease symptoms of depression and negative symptoms of schizophrenia. The only clinical study done on depressive patients by Huang et al. cannot be generalized due to certain inherent limitations. To date, there is no randomized controlled trial with add-on sarcosine to current antidepressant therapy to the best of our knowledge. So, we considered sarcosine can be the candidate drug for add-on therapy due to its multiple mechanisms on the glutaminergic system. Adding sarcosine to ongoing antidepressant therapy may either increase their response rate or decrease adverse drug reactions by decreasing the dose requirement or may show a quicker therapeutic effect. Hence, the present randomized controlled trial has been planned to evaluate the efficacy and safety of sarcosine as add-on therapy in major depressive disorder.

开始日期2021-08-26

申办/合作机构

All India Institute of Medical Sciences

IRCT20211022052836N1 / Completed早期临床1期IIT

Evaluation of the effectiveness of adding sarcosine to PMT (parental education management) treatment on the symptoms of coping disorder

开始日期2019-12-22

申办/合作机构

Isfahan University of Medical Sciences

NCT00977353 / Completed临床2期IIT

N-methylglycine (Sarcosine) for Treatment of Major Depressive Disorder

Major depressive disorder is a complex disease and most currently available antidepressants aiming at monoamine neurotransmission exhibit limited efficacy and cognitive effects. N-methyl-D-aspartate (NMDA), one subtype of glutamate receptors, plays an important role in learning and memory. N-methyl-D-aspartic acid (NMDA) enhancing agents, such as sarcosine (N-methylglycine), have been used as adjunctive therapy of schizophrenia. Sarcosine improved not only psychotic but also depressive symptoms in patients with schizophrenia. To confirm its antidepressant effect, the purpose of this study is to compare citalopram and sarcosine in efficacy for major depressive patients.

开始日期2009-04-01

申办/合作机构

中国医药大学附设医院

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100 项与肌氨酸相关的临床结果

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100 项与肌氨酸相关的转化医学

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100 项与肌氨酸相关的专利（医药）

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247

项与肌氨酸相关的文献（医药）

2024-10-01·Journal of Psychiatric Research

Efficacy and safety of add-on sarcosine in patients with major depressive disorder: A randomized controlled trial

Article

作者: Jena, Monalisa ; Mohapatra, Debadatta ; Padhan, Milan ; Mishra, Biswa Ranjan ; Maiti, Rituparna

2024-09-10·Metabolites

Sarcosine, Trigonelline and Phenylalanine as Urinary Metabolites Related to Visceral Fat in Overweight and Obesity.

Article

作者: Zantut-Wittmann, Denise Engelbrecht ; Magalhães, Alviclér ; Batista, Aline Lidiane ; Cavalcanti, Diogo Manuel Lopes de Paiva ; Gurgel, Aline Maria Cavalcante

The objective of the present study is to analyze the urinary metabolome profile of patients with obesity and overweight and relate it to different obesity profiles. This is a prospective, cross-sectional study in which patients with a body mass index (BMI) ≥25 kg/m were selected. Anthropometric data were assessed by physical examination and body composition was obtained by bioimpedance (basal metabolic rate, body fat percentile, skeletal muscle mass, gross fat mass and visceral fat). Urine was collected for metabolomic analysis. Patients were classified according to abdominal circumference measurements between 81 and 93, 94 and 104, and >104 cm; visceral fat up to 16 kilos and less than; and fat percentiles of <36%, 36-46% and >46%. Spectral alignment of urinary metabolite signals and bioinformatic analysis were carried out to select the metabolites that stood out. NMR spectrometry was used to detect and quantify the main urinary metabolites and to compare the groups. Seventy-five patients were included, with a mean age of 38.3 years, and 72% females. The urinary metabolomic profile showed no differences in BMI, abdominal circumference and percentage of body fat. Higher concentrations of trigonelline (p = 0.0488), sarcosine (p = 0.0350) and phenylalanine (p = 0.0488) were associated with patients with visceral fat over 16 kg. The cutoff points obtained by the ROC curves were able to accurately differentiate between patients according to the amount of visceral fat: sarcosine 0.043 mg/mL; trigonelline 0.068 mg/mL and phenylalanine 0.204 mg/mL. In conclusion, higher visceral fat was associated with urinary levels of metabolites such as sarcosine, related to insulin resistance; trigonelline, related to muscle mass and strength; and phenylalanine, related to glucose metabolism and abdominal fat. Trigonelline, sarcosine and phenylalanine play significant roles in regulating energy balance and metabolic pathways essential for controlling obesity. Our findings could represent an interesting option for the non-invasive estimation of visceral fat through biomarkers related to alterations in metabolic pathways involved in the pathophysiology of obesity.

2024-08-01·Biological Psychiatry

Finding the right dose: NMDAR modulating treatments for cognitive and plasticity deficits in schizophrenia and the role of pharmacodynamic target engagement

Review

作者: Kantrowitz, Joshua T. ; Kantrowitz, Joshua T ; Sehatpour, Pejman

Cognitive impairment associated with schizophrenia (CIAS) and related deficits in learning (plasticity) are amongst the leading causes of disability in schizophrenia. Despite this, there are no FDA approved treatments for CIAS, and the development of treatments has been limited by numerous Phase II/III failures of compounds that showed initial promise in small-scale studies. N-methyl-d-aspartate-type glutamate receptors (NMDAR) have been proposed to play an important role in schizophrenia; moreover, NMDAR has a well characterized role in cognition, learning and neuroplasticity. We review prior published clinical trials in CIAS focusing on NMDAR modulator treatments, focusing on published and recent developments of the use of novel NMDAR-modulating treatments for CIAS both alone and combined with plasticity/learning paradigms to enhance learning. We will use this discussion of prior studies to highlight the importance of incorporating pharmacodynamic target engagement biomarkers early in treatment development, which can help predict which compounds will succeed or fail in Phase III. A range of direct and indirect NMDAR modulators will be covered, including d-serine, d-cycloserine, memantine, glycine and "first generation" glycine transport inhibitors (GTI, e.g. sarcosine and bitopertin), as well as recent positive studies of iclepertin, a novel GTI and luvadaxistat, a D-amino acid oxidase inhibitor (DAAO-I) that increases brain d-serine levels and indirect non-invasive brain stimulation NMDAR modulating treatments. Several examples of successful use of pharmacodynamic target engagement biomarkers for dose/drug discovery will be emphasized, including mismatch negativity (MMN), auditory steady state (ASSR) and time-frequency event-related potential (TF-ERP) approaches.

项与肌氨酸相关的新闻（医药）

2024-03-21

·生物探索

Cell | 中国科学院赵岩团队揭示甘氨酸转运蛋白GlyT1的底物识别和抗精神分裂药物抑制机制

引言甘氨酸转运蛋白1 (GlyT1)通过清除突触间隙中的甘氨酸，在抑制性和兴奋性神经传递的调节中起着至关重要的作用。鉴于其与谷氨酸/甘氨酸共激活的NMDA受体(NMDARs)密切相关，GlyT1已成为治疗精神分裂症的中心靶点，精神分裂症通常与功能低下的NMDARs有关。2024年3月20日，中国科学院生物物理研究所赵岩团队在Cell 在线发表题为“Transport mechanism and pharmacology of the human GlyT1”的研究论文，该研究报道了GlyT1与底物甘氨酸和药物ALX-5407, SSR504734和PF-03463275结合的冷冻电镜结构。这些结构在转运循环的三种基本状态下被捕获—向外、封闭和内向—使得能够阐明与甘氨酸再摄取相关的构象变化的全面蓝图。此外，还确定了三个特定的容纳药物的口袋，为其抑制机制和选择性的结构基础提供了清晰的见解。总的来说，这些结构对底物和抗精神分裂症药物的转运机制和识别提供了重要的见解，从而为设计治疗精神分裂症的小分子提供了一个平台。甘氨酸是一种重要的神经递质，在中枢神经系统(CNS)中发挥多种功能。作为一种抑制性神经递质，它主要活跃于脑干和脊髓，在那里它参与了广泛的运动和感觉功能。然而，它也作为NMDA受体(NMDARs)的强制性共激动剂参与兴奋性神经传递甘氨酸的突触浓度主要受两种高亲和的钠和氯依赖性转运蛋白调节，甘氨酸转运蛋白1 (GlyT1) (SLC6A9) 和GlyT2 (SLC6A5) ，它们属于神经递质钠同向转运蛋白(NSS)家族这两种转运蛋白在神经系统中具有互补的分布和功能。与主要表达于甘氨酸神经末梢的GlyT2不同，GlyT1主要表达于星形胶质细胞和谷氨酸神经元中，并被认为通过影响协同激动剂甘氨酸的可用性来调节NMDARs的活性。GlyT1纯合子敲除小鼠会出现严重的神经运动缺陷，导致过早死亡，而GlyT1+/-杂合子小鼠，GlyT1水平降低50%，谷氨酸能功能受损，突出了GlyT1在抑制性和兴奋性神经传递中的关键功能作用。精神分裂症是一种严重的慢性精神疾病，患病率高达1%越来越多的证据表明NMDAR在精神分裂症的病理生理中起着关键作用。值得注意的是，NMDARs的开放通道阻滞剂可以在健康个体中诱导精神分裂症样症状。因此，增强NMDARs的功能已成为治疗精神分裂症的一种有前景的治疗策略。临床研究表明，NMDAR中甘氨酸位点的激动剂，如甘氨酸和D-丝氨酸，可能对治疗精神分裂症有益。因此，许多选择性GlyT1抑制剂被开发出来，旨在提高突触间隙中的甘氨酸浓度，间接增强NMDARs的活性。根据其化学结构，这些GlyT1选择性抑制剂可分为基于肌氨酸和非基于肌氨酸的抑制剂。肌氨酸是GlyT1的内源性抑制剂，不影响GlyT2。肌氨酸的衍生物，如ALX-5407可有效抑制GlyT1，特异性高。然而，基于肌氨酸的抑制剂的抑制作用往往是不可逆的，并导致严重的副作用。模式图（Credit: Cell）为了避免这一问题，已经开发了各种非肌氨酸衍生物抑制剂，包括以SSR504734为代表的甲基苯甲酸酯衍生GlyT1抑制剂，以PF-03463275为代表的杂芳酰胺GlyT1抑制剂，这些类别的药物目前正在进行上市前临床试验。尽管GlyT1与Cmpd1结合的晶体结构已经确定，但它只揭示了一个面向内的构象，还有许多机制有待阐明。其中包括底物甘氨酸识别、离子结合和转运周期中的构象变化的分子机制，这对于理解大脑中甘氨酸再摄取过程至关重要。此外，探索各种化学衍生物如何选择性地结合和抑制GlyT1是至关重要的，这对于进一步合理设计有效的、高度特异性的、可逆的GlyT1抑制剂来治疗精神分裂症至关重要。该研究确定了GlyT1结合底物甘氨酸(GlyT1Gly)、肌氨酸基抑制剂ALX-5407 (GlyT1ALX)、非肌氨酸基抑制剂SSR504734 (GlyT1SSR)和PF03463275 (GlyT1PF)的结构。这些结构稳定在三种不同的构象中，包括外向构象(GlyT1SSR/GlyT1PF)，封闭状态(GlyT1Gly)和内向构象(GlyT1ALX)。此外，借助[3h]甘氨酸摄取测定，能够清楚地证明特定的结构差异，使每种抑制剂能够区分GlyT1和GlyT2。该研究阐明了底物结合、构象变化的分子基础，以及抗精神分裂症药物的变构或竞争、可逆或不可逆结合模式，以及它们的选择性，为合理设计针对不同构象的强效、选择性和可逆药物提供了平台，从而为精神分裂症的治疗干预提供了潜在的治疗手段。原文链接https://www-cell-com.libproxy1.nus.edu.sg/cell/abstract/S0092-8674(24)00228-9责编|探索君排版|探索君文章来源|“iNature”End往期精选围观一文读透细胞死亡(Cell Death) | 24年Cell重磅综述（长文收藏版）热文Nature | 破除传统：为何我们需要重新思考肿瘤的命名方式热文Nature | 2024年值得关注的七项技术热文Nature | 自身免疫性疾病能被治愈吗？科学家们终于看到了希望热文CRISPR技术进化史 | 24年Cell综述

100 项与肌氨酸相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	肌氨酸	-	DB12519

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
抑郁症	临床2期	-	McLean Hospital, Inc.	-
强迫症	临床2期	-	McLean Hospital, Inc.	-
强迫症	临床2期	-	Merck & Co., Inc.	-
精神分裂症	临床2期	-	McLean Hospital, Inc.	-
精神分裂症	临床2期	-	Merck & Co., Inc.	-
抑郁症	药物发现	-	Merck & Co., Inc.	-

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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


137 (AUA2011)	N/A	遗传性前列腺癌7型 \| 疾病进展	92	SARCOSINE (Malignant tissue)	憲構繭簾餘憲艱觸鏇糧(齋築醖簾衊構壓憲蓋鑰) = 製夢網鏇鹽顧顧蓋夢窪壓襯築膚膚鏇範憲遞醖 (簾糧鹽製淵糧製廠選膚 )	不佳	2011-04-01