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更新于：2025-05-07

GLRA1

更新于：2025-05-07

基本信息

别名

GLRA1、Glycine receptor 48 kDa subunit、glycine receptor alpha 1

+ [5]

简介

Subunit of heteromeric glycine-gated chloride channels (PubMed:14551753, PubMed:23994010, PubMed:25730860, PubMed:37821459). Plays an important role in the down-regulation of neuronal excitability (PubMed:8298642, PubMed:9009272). Contributes to the generation of inhibitory postsynaptic currents (PubMed:25445488). Channel activity is potentiated by ethanol (PubMed:25973519). Potentiation of channel activity by intoxicating levels of ethanol contribute to the sedative effects of ethanol (By similarity).

关联

项与 GLRA1 相关的药物

Desflurane

地氟烷

靶点

ATP2C1 x GLRA1 x GRIA1

作用机制

ATP2C1 blockers [+2]

在研机构

Baxter Healthcare Corp. [+1]

原研机构

Baxter International, Inc.

在研适应症

麻醉

非在研适应症-

最高研发阶段批准上市

首次获批国家/地区

美国

首次获批日期1992-09-18

Sevoflurane

七氟烷

靶点

ATP2C1 x GABRA1 x GLRA1 x GRIA1

作用机制

ATP2C1 blockers [+3]

在研机构

AbbVie, Inc. [+4]

原研机构

AbbVie, Inc.

在研适应症

麻醉 [+3]

非在研适应症-

最高研发阶段批准上市

首次获批国家/地区

日本

首次获批日期1990-04-20

Isoflurane

异氟烷

靶点

ATP2C1 x GABRA1 x GLRA1 x GRIA1

作用机制

ATP2C1 blockers [+3]

在研机构

Baxter Healthcare Corp. [+1]

原研机构

Baxter Healthcare Corp.

在研适应症

麻醉

非在研适应症-

最高研发阶段批准上市

首次获批国家/地区

美国

首次获批日期1979-12-18

1,315

项与 GLRA1 相关的临床试验

NCT03643367

/ Not yet recruiting临床2期IIT

Sevoflurane Sedation: a Potentially Promising Immunomodulation in Patients with Septic Shock

Recent in vivo studies from others as well as the investigators group demonstrated that volatile anesthetics immunomodulate sepsis and improve outcome. Also, several clinical trials have convincingly shown that application of a volatile anesthetic provides protection in patients undergoing major surgery.
Patients with sepsis are intubated and ventilated and therefore need sedation. So far, most ICU centers use intravenously applied sedatives in these patients. In the proposed study, we will switch sedation from an intravenous to a volatile anesthetic for a short period of time to explore if sepsis markers improve within the following 120 hours upon sevoflurane conditioning.

开始日期2026-01-01

申办/合作机构

University of Zurich

[+2]

NCT06832683

/ Not yet recruitingN/AIIT

Comparison of the Efficacy of Intravenous Propofol-Ketamine and Sevoflurane Administered Via Face Mask in Children Undergoing Magnetic Resonance Imaging: A Prospective, Randomized, Parallel-Group Study

Magnetic resonance imaging (MRI) is becoming increasingly important in the diagnosis and follow-up of pediatric diseases. However, successful MRI requires complete and prolonged immobility, which can be challenging for young children and infants. To overcome this challenge, various anesthesia techniques are employed by anesthesiologists. The ideal anesthesia method for children during MRI should be both safe and enable rapid recovery, allowing the child to remain still during the procedure while minimizing risks during the recovery period.
**Sevoflurane has become a popular choice for this purpose due to its rapid onset, limited respiratory side effects at low concentrations, reduced airway irritation, and hemodynamic stability. However, propofol and ketamine, used as an alternative sedation method, are also being increasingly utilized during these procedures. The major side effects of propofol include respiratory depression, apnea, loss of protective reflexes, and hemodynamic instability. To minimize these side effects, some experts recommend the combined use of propofol and ketamine. This combination provides effective sedation while also contributing to a reduction in side effects.
In this context, the aim of our study is to compare the efficacy of intravenous propofol and ketamine with sevoflurane administered via a face mask during pediatric MRI.

开始日期2025-07-01

申办/合作机构-

NCT06457958

/ Withdrawn临床4期IIT

The Effect of Sevoflurane and Desflurane Anesthetic Agents Used in Elective Cholecystectomy Surgery on Heme Oxygenase-1 MRNA Expression and Heme Oxygenase-1 Protein Levels: a Comparative Prospective Study

General anesthesia is routinely administered to patients who undergo elective cholecystectomy. The most commonly used inhalation agents during general anesthesia are sevoflurane and desflurane. Participants who will undergo elective cholecystectomy surgery and meet the eligibility criteria will be randomized. Participants will be divided into two groups. One group will receive sevoflurane, and the other group will receive desflurane. Preoperative and postoperative blood samples will be taken from the participants. After the sample collection process is completed, the ELISA method will be used for measuring blood heme oxygenase-1 protein levels, and the PCR technique will be used for measuring blood heme oxygenase-1 mRNA gene expression. The increase in amounts between the two groups will be compared. This study aims to demonstrate the effects of the most commonly used inhalation agents on the levels of heme oxygenase-1 enzyme, which has been shown to be an important enzyme in cellular protection mechanisms, as well as on mRNA gene expression, and to determine which agent may be more effective in preventing cellular damage at the molecular level.

开始日期2025-06-01

申办/合作机构

Türkiye Bilimsel ve Teknolojik Arastirma Kurumu

100 项与 GLRA1 相关的临床结果

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100 项与 GLRA1 相关的转化医学

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0 项与 GLRA1 相关的专利（医药）

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422

项与 GLRA1 相关的文献（医药）

2025-01-01·Molecular Psychiatry

DNA methylation and histone modifications associated with antipsychotic treatment: a systematic review

Review

作者: Greenway, Steven C. ; Greenway, Steven C ; Bousman, Chad ; Marques, Diogo ; Vaziri, Nazanin

Antipsychotic medications are essential when treating schizophrenia spectrum and other psychotic disorders, but the efficacy and tolerability of these medications vary from person to person. This interindividual variation is likely mediated, at least in part, by epigenomic processes that have yet to be fully elucidated. Herein, we systematically identified and evaluated 65 studies that examine the influence of antipsychotic drugs on epigenomic changes, including global methylation (9 studies), genome-wide methylation (22 studies), candidate gene methylation (16 studies), and histone modification (18 studies). Our evaluation revealed that haloperidol was consistently associated with increased global hypermethylation, which corroborates with genome-wide analyses, mostly performed by methylation arrays. In contrast, clozapine seems to promote hypomethylation across the epigenome. Candidate-gene methylation studies reveal varying effects post-antipsychotic therapy. Some genes like Glra1 and Drd2 are frequently found to undergo hypermethylation, whereas other genes such as SLC6A4, DUSP6, and DTNBP1 are more likely to exhibit hypomethylation in promoter regions. In examining histone modifications, the literature suggests that clozapine changes histone methylation patterns in the prefrontal cortex, particularly elevating H3K4me3 at the Gad1 gene and affecting the transcription of genes like mGlu2 by modifying histone acetylation and interacting with HDAC2 enzymes. Risperidone and quetiapine, however, exhibit distinct impacts on histone marks across different brain regions and cell types, with risperidone reducing H3K27ac in the striatum and quetiapine modifying global H3K9me2 levels in the prefrontal cortex, suggesting antipsychotics demonstrate selective influence on histone modifications, which demonstrates a complex and targeted mode of action. While this review summarizes current knowledge, the intricate dynamics between antipsychotics and epigenetics clearly warrant more exhaustive exploration with the potential to redefine our understanding and treatment of psychiatric conditions. By deciphering the epigenetic changes associated with drug treatment and therapeutic outcomes, we can move closer to personalized medicine in psychiatry.

2024-12-01·Biophysical Reports

Structural studies of the human α1 glycine receptor via site-specific chemical cross-linking coupled with mass spectrometry

Article

作者: Donelan, Chelsee A ; Lapinsky, David J ; Veeramachaneni, Rathna J ; Aggarwal, Shaili ; Cascio, Michael ; Tomcho, Kayce A

By identifying distance constraints, chemical cross-linking coupled with mass spectrometry (CX-MS) can be a powerful complementary technique to other structural methods by interrogating macromolecular protein complexes under native-like conditions. In this study, we developed a CX-MS approach to identify the sites of chemical cross-linking from a single targeted location within the human α1 glycine receptor (α1 GlyR) in its apo state. The human α1 GlyR belongs to the family of pentameric ligand-gated ion channel receptors that function in fast neurotransmission. A single chemically reactive cysteine was reintroduced into a Cys null α1 GlyR construct at position 41 within the extracellular domain of human α1 homomeric GlyR overexpressed in a baculoviral system. After purification and reconstitution into vesicles, methanethiosulfonate-benzophenone-alkyne, a heterotrifunctional cross-linker, was site specifically attached to Cys41 via disulfide bond formation. The resting receptor was then subjected to UV photocross-linking. Afterward, monomeric and oligomeric α1 GlyR bands from SDS-PAGE gels were trypsinized and analyzed by tandem MS in bottom-up studies. Dozens of intrasubunit and intersubunit sites of α1 GlyR cross-linking were differentiated and identified from single gel bands of purified protein, showing the utility of this experimental approach to identify a diverse array of distance constraints of the α1 GlyR in its resting state. These studies highlight CX-MS as an experimental approach to identify chemical cross-links within full-length integral membrane protein assemblies in a native-like lipid environment.

2024-12-01·Molecular and Cellular Neuroscience

The mRNA expression profile of glycine receptor subunits alpha 1, alpha 2, alpha 4 and beta in female and male mice

Article

作者: Magnusson, Kajsa A. ; Lagerström, Malin C ; Andréasson, Linn ; Ceder, Mikaela M. ; Ceder, Mikaela M ; Lagerström, Malin C. ; Magnusson, Kajsa A ; Lindström, Teresa ; Henriksson, Katharina ; Wiggins, Oskar ; Weman, Hannah M. ; Weman, Hannah M

Glycine receptors are ligand-gated chloride-selective channels that control excitability in the central nervous system (CNS). Herein, we have investigated the mRNA expression of the glycine receptor alpha 1 (Glra1), alpha 2 (Glra2), alpha 4 (Glra4) and the beta (Glrb) subunits, in adult female and male mice. Single-cell RNA sequencing data re-analysis of the Zeisel et al. (2018) dataset indicated widespread expression of Glra1, Glra2 and Glrb in the CNS, while only a few cells in the cortex, striatum, thalamus, midbrain and the spinal cord expressed Glra4. Highest occurrence of Glra1, Glra2 and Glrb were found in the brainstem. Moreover, Glra1 and Glrb were revealed to have the highest occurrences in the spinal cord of the investigated subunits. However, both Glra2 and Glrb had a more widespread expression in the CNS compared with Glra1 and Glra4. Bulk quantitative real-time-PCR (qRT-PCR) analysis revealed Glra1 expression in the hypothalamus, thalamus, brainstem and the spinal cord, and widespread, but low, Glra2 and Glrb expression in the CNS. Moreover, Glrb could be detected in a few visceral organs. Additionally, females and males were found to express Glra1, Glra2 and Glrb differently in certain brain areas such as the brainstem. Expression levels of Glra4 were too low to be detected using qRT-PCR. Lastly, RNAscope spatially validated the expression of Glra1, Glra2 and Glrb in the areas indicated by the single-cell and bulk analyses, and further revealed that Glra4 can be detected in the cortex, amygdala, hypothalamus, thalamus, brainstem, especially the cochlear nucleus, and in the spinal cord.

项与 GLRA1 相关的新闻（医药）

2025-04-25

·梅斯医学

一有声音就僵硬不动，12岁女孩10年没查出病因，医生：真是被吓的！

12岁的明明（化名）从7个月大起就开始“对声音过敏”——一听到陌生声音或被轻轻碰一下，立马身体僵硬、翻白眼，甚至呼吸暂停，家人以为是“吓到了”。随着年龄增长，症状越来越频繁，尤其是在陌生、嘈杂或空旷环境下，明明会突然全身僵硬，像被“冻结”一般，无法行动，甚至因此反复跌倒受伤。这些突如其来的发作，让她不敢出门、不愿上学，逐渐变得焦虑胆怯。家长带她辗转多家医院，排除了癫痫、神经肌肉病和心脏病，却始终查不出真正原因。明明到底怎么了？接诊医生为明明进行了详细的病史采集及相关检查，发现头颅磁共振成像、多种实验室检测均无异常，多次行视频脑电图发作期未见癫痫样放电，发作间期无异常。基因检查发现了明明的11号染色体上的 SLC6A5基因存在c.643T>C（p.W215R）杂合变异，终于发现了关键，确诊为：过度惊吓反应症(Startle disease spectrum disorders）。具有遗传异质性过度惊吓反应症是一种具有遗传异质性的常染色体显性或隐性遗传病，主要由抑制性甘氨酸神经传递缺陷所致，甘氨酸受体相关基因的变异可引起氯离子通道开关异常，进而导致突触抑制失效，表现出过度惊吓反应。基于其潜在的遗传学病因，OMIM数据库已将遗传性过度惊吓症分为4型，最常见的致病基因为 GLRA1，于1993年被Shiang等首先提出。另外还有一些比较少见的致病基因，如 GPHN、 ARHGEF9等。临床表现过度惊吓反应症主要的临床特征为：新生儿期及婴儿期起病，少数可在宫内起病。多由不可预料的外界刺激（听觉、视觉或触觉等）后产生过度的惊吓反应，这种反应不能自主适应。宫内期表现为频繁的发作样异常胎动；新生儿期表现为夸张的惊恐样表情，四肢抖动，烦躁不安，肌张力增高，肌肉僵直，身体呈弓状，多伴嘴唇青紫，呼吸暂停，甚至窒息死亡；婴儿期与新生儿期大同小异，但可发现患儿上述表现时意识清晰。多数患儿症状在婴儿期逐渐缓解甚至消失，个别患儿可持续至成年甚至终身存在，但随着年龄的增长，临床表现逐渐减轻。诊断点鼻试验阳性（叩击患儿鼻尖或上唇导致面部肌肉收缩同时伴有头后仰或身体僵硬的反应，且多次试验无适应性）是诊断该疾病的特异性方法。基因检测是目前唯一的确诊手段，由于对该病的认识不足，极易被误诊为癫痫。视频脑电图是将过度惊吓反应症与惊吓性癫痫等癫痫类疾病进行鉴别最简单直观的方法。过度惊吓反应症患者（不包括其中合并有癫痫者）的视频脑电图强直发作期可表现为广泛性强直性肌电伪差遮盖脑波，不伴痫样放电或发作期背景改变；发作间期多正常或存在非特异性表现。治疗氯硝西泮是治疗该疾病的首选药物，另外还有使用抗发作药物治疗该疾病的报道，如左乙拉西坦、苯巴比妥、氨己烯酸、卡马西平等，但效果尚未明确。本病虽然一般预后较好，但处理不及时患儿可出现呼吸困难及窒息甚至猝死。参考资料：1.孙敏，张新，徐那,等. 过度惊吓反应症1例临床及遗传学分析. 中华神经科杂志，2023，56(07):780-786.2.韩瑞，张晓莉，贾天明,等. 过度惊吓反应症3例患儿的临床及遗传学分析. 中华医学遗传学杂志，2024，41(06):720-724.3.李慧，杨志仙，薛姣,等. 过度惊吓反应症一例的临床及分子遗传学分析并文献复习. 中华儿科杂志，2017，55(02):120-124.来源 | 梅斯医学编辑 | wanny神经系统罕见病交流群↓点击下方“阅读原文”，下载梅斯医学APP吧！

核酸药物

2023-01-04

·PRNewswire

Sedana Medical receives FDA Fast Track Designation in the United States

STOCKHOLM, Jan. 4, 2023 /PRNewswire/ -- Sedana Medical AB (publ) (SEDANA: FN Stockholm) today announces that the U.S. Food and Drug Administration (FDA) has granted Fast Track Designation (FTD) for the evaluation of isoflurane via the Sedaconda ACD-S device for sedation of mechanically ventilated patients in the intensive care (ICU) setting. Fast Track is a process designed to facilitate the development, and expedite the review of therapies that treat serious conditions and fill an unmet medical need. The purpose is to get important new therapies to the patient earlier. Clinical programs with Fast Track Designation may benefit from frequent communication with the FDA throughout the development and review process and may be eligible to Accelerated Approval and Priority Review if relevant criteria are met. Another possible benefit may be a Rolling Review, which means that completed sections of the New Drug Application (NDA) can be submitted for review by FDA, rather than waiting until every section of the NDA is completed. "The FDA's decision to grant Fast Track Designation underscores the potential for our product candidates to address a serious unmet need and bring meaningful benefits to ventilated patients in intensive care. We are fully committed to work even more closely with FDA to bring our therapy to US patients as soon as possible," said Johannes Doll, CEO of Sedana Medical. "This excellent news represents an important step forward in our highest potential market." Sedana Medical is aiming for a combination registration of the medical device Sedaconda ACD and the pharmaceutical isoflurane for sedation of mechanically ventilated intensive care patients in the United States. Two identical Phase III studies, INSPiRE-ICU 1 and 2, are ongoing with the objective to confirm the efficacy and safety of inhaled sedation with isoflurane delivered via Sedaconda ACD in intensive care. Sedana Medical will engage in discussions with the FDA on how the development program can benefit from the FTD. At present, the guidance regarding the timeline is unchanged: assuming rapid enrolment of patients and successful trials, Sedana Medical expects the NDA submission in 2024 and a launch in early 2025. About the studies INSPiRE-ICU 1 and INSPiRE-ICU 2 (SED003 and SED004) The INSPiRE-ICU (Inhaled Sedation vs Propofol in Respiratory failure) studies are two identical phase III studies aiming to confirm the efficacy and safety of inhaled isoflurane, delivered via the Sedaconda ACD, for the sedation of adult mechanically ventilated ICU patients, in comparison to intravenous infusion of propofol. The studies will enrol a total of 470 adult patients across 25-30 sites in the US. Patient enrolment is expected to be completed in 2023. The primary endpoint is the proportion of time spent within the target range of sedation depth in absence of rescue sedation, as assessed according to the Richmond Agitation Sedation Scale (RASS). In addition, the studies will investigate several secondary endpoints, including the use of opioids, the wake-up time, the cognitive recovery after end of sedation, and the spontaneous breathing effort. The assessments will be performed by blinded assessors to meet the requirements of the FDA. Further information on the studies is available at (NCT05312385 for SED003 and NCT05327296 for SED004). For additional information, please contact: Johannes Doll, CEO, +46 76 303 66 66 Johan Spetz, CFO, +46 730 36 37 89 [email protected] Sedana Medical is listed on Nasdaq First North Growth Market in Stockholm. The company's Certified Adviser is Erik Penser Bank, +46 8 463 83 00, [email protected] About Sedana Medical Sedana Medical AB (publ) is a pioneer medtech and pharmaceutical company focused on inhaled sedation to improve the patient's life during and beyond sedation. Through the combined strengths of the medical device Sedaconda ACD and the pharmaceutical Sedaconda (isoflurane), Sedana Medical provides inhaled sedation for mechanically ventilated patients in intensive care. Sedana Medical has direct sales in Benelux, France, Germany, Great Britain, the Nordic, and Spain. In other parts of Europe as well as in Asia, Australia, Canada, and South- and Central America, the company works with external distributors. Sedana Medical was founded in 2005, is listed on Nasdaq First North Growth Market (SEDANA) and headquartered in Stockholm, Sweden. The following files are available for download: SOURCE Sedana Medical

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