更新于：2024-11-21

Acetylleucine

乙酰亮氨酸

更新于：2024-11-21

概要

概要

基本信息

药物类型

小分子化药

别名

+ [5]

靶点-

作用机制-

治疗领域

神经系统疾病耳鼻咽喉疾病

在研适应症

眩晕

非在研适应症-

原研机构-

在研机构-

非在研机构-

最高研发阶段批准上市

首次获批日期-

最高研发阶段(中国)-

特殊审评-

登录后查看时间轴

结构

分子式C10H22N2O4

InChIKeyRUNLLFIZXARADP-UHFFFAOYSA-N

CAS号149-90-6

查看全部结构式(2)

关联

项与乙酰亮氨酸相关的临床试验

EUCTR2007-000562-21-FR / Not yet recruiting临床2期IIT

Effects of TANGANIL (three 500 mg tablets twice daily) on postural disturbances in the elderly.

开始日期2007-09-19

申办/合作机构-

100 项与乙酰亮氨酸相关的临床结果

登录后查看更多信息

100 项与乙酰亮氨酸相关的转化医学

登录后查看更多信息

100 项与乙酰亮氨酸相关的专利（医药）

登录后查看更多信息

项与乙酰亮氨酸相关的文献（医药）

2024-09-01·Expert Review of Neurotherapeutics

The importance of synthetic pharmacotherapy for recessive cerebellar ataxias

Review

作者: Beaudin, Marie ; Dupre, Nicolas ; Manto, Mario

INTRODUCTIONThe last decade has witnessed major breakthroughs in identifying novel genetic causes of hereditary ataxias, deepening our understanding of disease mechanisms, and developing therapies for these debilitating disorders.AREAS COVEREDThis article reviews the currently approved and most promising candidate pharmacotherapies in relation to the known disease mechanisms of the most prevalent autosomal recessive ataxias. Omaveloxolone is an Nrf2 activator that increases antioxidant defense and was recently approved for treatment of Friedreich ataxia. Its therapeutic effect is modest, and further research is needed to find synergistic treatments that would halt or reverse disease progression. Promising approaches include upregulation of frataxin expression by epigenetic mechanisms, direct protein replacement, and gene replacement therapy. For ataxia-telangiectasia, promising approaches include splice-switching antisense oligonucleotides and small molecules targeting oxidative stress, inflammation, and mitochondrial function. Rare recessive ataxias for which disease-modifying therapies exist are also reviewed, emphasizing recently approved therapies. Evidence supporting the use of riluzole and acetyl-leucine in recessive ataxias is discussed.EXPERT OPINIONAdvances in genetic therapies for other neurogenetic conditions have paved the way to implement feasible approaches with potential dramatic benefits. Particularly, as we develop effective treatments for these conditions, we may need to combine therapies, consider newborn testing for pre-symptomatic treatment, and optimize non-pharmacological approaches.

2009-01-01·Audiology and Neurotology4区 · 医学

Effects of Acetyl-DL-Leucine in Vestibular Patients: A Clinical Study following Neurotomy and Labyrinthectomy

4区 · 医学

Article

作者: Dubreuil, C. ; Ferber-Viart, C. ; Vidal, P. P.

For 40 years, the amino acid acetyl-DL-leucine (or isoleucine – Tanganil®) has been used in clinical practice to reduce imbalance and autonomic manifestations associated with acute vertigo crises. In animal models, acetyl-DL-leucine accelerates vestibular compensation following unilateral labyrinthectomy, and has only minor effects on normal vestibular function. Our work in animal models suggested that acetyl-DL-leucine acted mainly on abnormally hyperpolarized and/or depolarized vestibular neurons by restoring their membrane potential towards a mean value of –65 to –60 mV. Acute vestibular disorders are associated with asymmetrical spontaneous activities of vestibular neurons, so this previous study suggested that acetyl-DL-leucine may reduce acute, vestibular-related imbalances in humans. To test this hypothesis, we investigated the efficacy of acetyl-DL-leucine during the acute stage following neurotomy or labyrinthectomy in patients undergoing surgery for unilateral vestibular acoustic neurinoma, or suffering from unilateral and intractable Ménière’s disease. By clinical testing of the vestibular function, patients were categorized according to the degree of compensation of the vestibular deafferentation prior to surgery. For patients who had achieved a close to perfect compensation before surgery, acetyl-DL-leucine had minor or no effect after surgery. For patients who displayed residual vestibular function before surgery, acetyl-DL-leucine eased the static vestibular syndromes, which followed neurotomy. Our findings tend to confirm the view that acetyl-DL-leucine mainly acts, in humans, on abnormally hyperpolarized and/or depolarized vestibular neurons by restoring their membrane potential towards normal values; this is consistent with findings in guinea pigs following unilateral labyrinthectomy. Moreover, it suggests that the degree of caloric paresis of the patients before neurotomy is useful both to predict the outcome of any acute vestibular syndrome following neurotomy and to assess the potential value of the administration of acetyl-DL-leucine to treat any such syndrome.

2008-07-03·Journal of Vestibular Research4区 · 医学

Effects of vestibular training on motion sickness, nystagmus, and subjective vertical

4区 · 医学

Article

作者: Deguine, Olivier ; Traon, Anne Pavy-Le ; Bourg, Mathieu ; Clément, Gilles

Pitch head-and-trunk movements during constant velocity rotation are a provocative vestibular stimulus that produces vertigo and nausea. When exposed to this stimulus repeatedly, motion sickness symptoms diminish as the subjects habituate. Acetylleucine is a drug that is used to treat acute vestibular vertigo. In this study, we wanted to ascertain whether this drug (a) lessened motion sickness or delayed habituation; (b) accelerated the recovery following habituation; and (c) whether changes in the subjective vertical accompanied habituation. Twenty subjects were administered acetylleucine or placebo in a double-blind study during a five-day vestibular training. Horizontal vestibulo-ocular reflex, optokinetic nystagmus, smooth pursuit, and subjective visual vertical were evaluated before, during, and up to two months after the vestibular training. Based on Graybiel's diagnostic criteria, motion sickness decreased steadily in each vestibular training session, and there was no difference between the scores in the acetylleucine and placebo groups. Post-rotatory nystagmus peak velocity and time constant also declined in both groups at the same rate. Thus, acetylleucine neither reduced the nausea associated with this provocative stimulus, nor hastened the acquisition or retention of vestibular habituation of motion sickness and nystagmus. There was no difference in optokinetic nystagmus and smooth pursuit between the acetylleucine and placebo groups. However, subjects showed larger error in the subjective visual vertical after habituation, which indicates that spatial orientation is also affected by vestibular training.

项与乙酰亮氨酸相关的新闻（医药）

2024-10-11

·药精通Bio

2024 FDA已批准34款新药！其中Q3新增13款！

OTC2024类器官前沿应用与3D细胞培养论坛圆满落幕，点击图片可查看会后报告，咨询OTC2025类器官论坛请联系：王晨 180 1628 8769 🧴Berdazimer （Zelsuvmi），一种用于治疗局部传染性软疣的一氧化氮（NO）释放剂。💉头孢吡肟/恩美唑巴坦（Exblifep），一种包含头孢吡肟和恩美唑巴坦的固定剂量组合，用于治疗尿路感染。 💉LetibotulinumtoxinA （Letybo），一种纯化的 A 型肉毒杆菌神经毒素蛋白复合物，用于改善眉间纹的外观。💉替雷利珠单抗（Tivembra）是一种 IgG4 变体 PD-1 mAb，适用于治疗不可切除、局部晚期或转移性食管鳞状细胞癌。💊Resmetirom （Rezdiffra），一种甲状腺激素受体 β （NR1A2）激动剂用于治疗非肝硬化性非酒精性脂肪性肝炎。 💊Aprocitentan （Tryvio），一种用于治疗高血压的内皮素受体拮抗剂。💊Givinostat （Duvyzat），一种组蛋白脱乙酰酶抑制剂，用于治疗杜氏肌营养不良症。💉 Sotatercept （Winrevair），一种用于治疗肺动脉高压的激活素信号抑制剂。💊 Vadadustat （Vafseo），一种口服缺氧诱导因子脯氨酰羟化酶抑制剂，用于治疗成人与 CKD 相关的症状性贫血。💊 Danicopan （Voydeya），补体因子 D 抑制剂，用于治疗 PNH 患者的血管外溶血。 💉 Ceftobiprole medocaril （Zevtera）是一种广谱头孢菌素抗菌剂，适用于某些类型的肺炎、菌血症和皮肤感染。💉 Pegulicianine （Lumisight），一种用于乳腺癌荧光成像的光学成像剂。💉 Nogapendekin alfa inbakicept （Anktiva）是一种白细胞介素 15 受体激动剂与卡介苗（BCG）的组合，用于治疗膀胱癌。 💊 Tovorafenib （Ojemda），一种 II 型 RAF 激酶抑制剂，用于治疗具有 BRAF 基因突变的小儿低级别胶质瘤。💊 Mavorixafor （Xolremdi），一种用于治疗 WHIM 综合征的 CXCR4 拮抗剂。💉 Tarlatamab （Imdelltra）是一种靶向 DLL3 和 CD3 的双特异性单克隆抗体和 T 细胞接合器，用于治疗广泛期小细胞肺癌。💉 Imetelstat （Rytelo），一种寡核苷酸端粒酶抑制剂，用于治疗骨髓增生异常综合征伴输血依赖性贫血。 💊 Elafibranor （Iqirvo），一种双重 PPARα/δ 激动剂，用于治疗原发性胆汁性胆管炎。🧴Sofpironium （Sofdra），一种用于治疗多汗症的 M3 毒蕈碱受体抑制剂。💉 Crovalimab （Piasky），一种用于治疗阵发性睡眠性血红蛋白尿症的补体 C5 抑制性 mAb。🫁 Ensifentrine，一种用于治疗 COPD 的双重 PDE3/4 抑制剂。💉Donanemab-azbt，一样β淀粉样蛋白（Aβ）定向抗体，用于治疗阿尔兹海默病。💊Deuruxolitinib，一种JAK1和JAK2抑制剂，用于治疗严重斑秃。💊Vorasidenib，一种 IDH1 和 IDH2 抑制剂，用于治疗具有易感 IDH1 或 IDH2 突变的 2 级星形细胞瘤或少突胶质细胞瘤。💉Palopegteriparatide，一种用于治疗甲状旁腺功能亢进症的甲状旁腺激素类似物。💉Nemolizumab，一种用于治疗结节性痒疹的 IL-31 受体 α 拮抗剂。 💊Seladelpar 是一种 PPAR-δ 激动剂，用于单独治疗原发性胆汁性胆管炎或与熊去氧胆酸联合治疗。💉Axatilimab 是一种 CSF-1R mAb，用于降低慢性移植物抗宿主病患者的致病性巨噬细胞活性。💊Lazertinib，一种 EGFRm 激酶抑制剂，与 amivantamab 联合用于治疗具有 EGFR 突变的非小细胞肺癌。💉Lebrikizumab，一种抗 IL-13 的 IgG4 mAb，用于治疗中度至重度特应性皮炎。💊Arimoclomol 是一种热休克蛋白共诱导剂，用于与 miglustat 联合治疗 C 型尼曼-匹克病的神经系统症状。💊L-乙酰亮氨酸，亮氨酸的一种改良形式，用于治疗 C 型尼曼-匹克病患者的神经系统症状。💊Xanomeline 和 trospium chloride，联合双重 M 1 - 和 M 4 - 选择性毒蕈碱受体激动剂和毒蕈碱受体拮抗剂，用于治疗精神分裂症。 💉Flurpiridaz F-18，一种用于评估心肌缺血和梗死的放射性诊断药物Picture from Chris De Savi 文章来源：早研早聊参考素材：素材来源官方媒体/网络新闻 END 免责声明：本文仅作知识交流与分享及科普目的，不涉及商业宣传，不作为相关医疗指导或用药建议。文章如有侵权请联系删除。 OTC2024类器官前沿应用与3D细胞培养论坛圆满落幕，点击图片可查看会后报告，咨询OTC2025类器官论坛请联系：王晨 180 1628 8769

上市批准

2024-09-02

·药明康德

9月3款创新药有望获FDA批准

根据PDUFA的预期目标日期，预计9月，美国FDA将对3款创新药物的批准做出监管决定，本文将对这些疗法进行相关介绍。适应症：C型尼曼匹克病（NPC）公司名称：Zevra Therapeutics Arimoclomol是一款口服、潜在“first-in-class”的细胞热休克反应共诱导剂，开发用以治疗NPC。该疗法曾获FDA授予孤儿药资格、快速通道资格、突破性疗法认定以及罕见儿科疾病资格。NPC是一种极为罕见、不可逆转的神经退行性溶酶体贮积病，其特点是胆固醇在细胞内的转运出现缺陷，胆固醇不能正常地离开内吞途径进入内质网从而积聚在溶酶体内，最终导致这些物质在包括脑组织在内的各种组织中积累。该疾病由NPC1或NPC2基因的突变所引起，这些基因负责制造溶酶体蛋白。患者的主要神经损伤表现为语言、认知、吞咽、行走和精细运动技能方面的障碍。 Zevra Therapeutics在今年4月公布arimoclomol用以治疗NPC的长期、真实世界数据。截至2023年7月19日，共有26名患者在基线时记录了5个领域的NPC临床严重性量表（5DNPCCS）评分，并且有超过1年的随访记录。这些患者接受arimoclomol治疗的平均时间为21个月（范围为12至32个月），其中69%（18/26）的患者同时使用了miglustat药物。数据显示，接受arimoclomol治疗的成人患者，无论是否同时使用miglustat，在两年的治疗和随访期间，整体病情保持稳定。治疗的安全性与此前2/3期研究中的观察结果一致，未发现新的不良事件。今年8月初，美国FDA遗传代谢疾病咨询委员会（GeMDAC）以11票赞成、5票反对的结果认为，arimoclomol的试验数据支持其用于治疗NPC患者。适应症：C型尼曼匹克病公司名称：IntraBio Acetylleucine是一种经过修饰的亮氨酸，开发为口服疗法。通过与广泛表达的单羧酸转运蛋白（monocarboxylate transporters）结合，acetylleucine能够有效输送至全身各组织，包括穿越血脑屏障。在多项研究中，包括C型尼曼匹克病的动物模型和观察性临床病例，acetylleucine显示出积极的神经症状改善效果以及神经保护的疾病修饰作用。 Acetylleucine的新药申请获得了美国FDA的优先审评资格，申请的主要依据是关键3期临床试验IB1001-301的结果。该试验主要评估了acetylleucine在治疗NPC患者12周后的疗效，特别是对患者共济失调评估与评分量表（SARA）的影响。数据显示，试验达到了所有主要和关键次要终点。具体而言，药物组患者的SARA评分相比安慰剂组有统计学上显著且具临床意义的改善，组间差异达到1.37分（药物组减少1.97分，安慰剂组减少0.60分；p<0.001）。在次要终点方面，药物组患者在修订后的共济失调评估与评分量表（mSARA）上减少了1.66分，而安慰剂组仅减少0.67分（p<0.001）。此外，药物组在研究者临床总体变化印象评分（CGI-C）上的改善也显著优于安慰剂组，前者减少了0.7分，而后者则增加了0.1分（p<0.001）。Acetylleucine在试验中表现出良好的安全性和耐受性，未发现药物相关的严重不良事件。这一研究的结果已于2024年2月发表在《新英格兰医学杂志》上。适应症：精神分裂症公司名称：百时美施贵宝今年4月，百时美施贵宝公布3期临床试验EMERGENT-4的最新中期数据。结果显示，试验52周时，KarXT能显著改善精神分裂症患者所有症状的疗效指标。根据阳性和阴性综合征量表（PANSS）评分，在开放标签延长期结束时，超过75%的患者症状改善超过30%，与基线（98.4分）相比平均减少33.3分。此外，受试者的临床整体印象-严重程度（CGI-S）评分与基线（5.2分）相比平均改善了1.7分，从基线时的"明显不适"转变为一年后的"中度不适"或"轻度不适"。 KarXT是一款在研口服M1/M4型毒蕈碱乙酰胆碱受体激动剂，正在开发用于治疗精神和神经系统疾病，包括精神分裂症和痴呆相关精神病性障碍，具有潜力成为首款非靶向多巴胺能与5-羟色胺能信号通路，并具双重机制的新式药物。KarXT由xanomeline和trospium chloride两种有效成分构成，旨在激活大脑中的毒蕈碱型乙酰胆碱受体的同时，减少对外周毒蕈碱型乙酰胆碱受体的作用。通过刺激毒蕈碱受体M1和M4受体，xanomeline可缓解负面症状，如冷漠、社会驱动力减少、提高认知能力，并对改善其它精神症状，如幻觉和妄想很有帮助。而季铵盐化合物trospium chloride为毒蕈碱受体拮抗剂，可抑制xanomeline于外周神经中的副作用。根据新闻稿，如果获得批准，KarXT将成为数十年来用于治疗精神分裂症的首个新机制药物。参考资料： [1] Zevra Therapeutics Presents New Data on the Long-Term Safety and Efficacy of Arimoclomol as a Treatment for Niemann-Pick Disease Type C at the SIMD 45th Annual Meeting. Retrieved August 30, 2024 from https://investors.zevra.com/news-releases/news-release-details/zevra-therapeutics-presents-new-data-long-term-safety-and [2] FDA Advisory Committee Votes Favorably that the Data Support Arimoclomol as Effective Treatment for Patients with Niemann-Pick Disease Type C. Retrieved August 30, 2024 from https://investors.zevra.com/news-releases/news-release-details/fda-advisory-committee-votes-favorably-data-support-arimoclomol [3] IntraBio Announces U.S. FDA Accepts New Drug Application for IB1001 for the Treatment of Niemann-Pick Disease Type C. Retrieved August 30, 2024 from https://www.accesswire.com/846963/intrabio-announces-us-fda-accepts-new-drug-application-for-ib1001-for-the-treatment-of-niemann-pick-disease-type-c [4] Positive Pivotal Trial Results of IB1001 for the Treatment of Niemann-Pick Disease Type C. Retrieved August 30, 2024 from https://intrabio.com/news/intrabio-announces-positive-pivotal-trial-results-of-ib1001-for-the-treatment-of-niemann-pick-disease-type-c/ [5] Bristol Myers Squibb Presents New Interim Long-Term Efficacy Data from the EMERGENT-4 Trial Evaluating KarXT in Schizophrenia at the 2024 Annual Congress of the Schizophrenia International Research Society. Retrieved April 8, 2024, from https://news.bms.com/news/corporate-financial/2024/Bristol-Myers-Squibb-Presents-New-Interim-Long-Term-Efficacy-Data-from-the-EMERGENT-4-Trial-Evaluating-KarXT-in-Schizophrenia-at-the-2024-Annual-Congress-of-the-Schizophrenia-International-Research-Society/default.aspx 内容来源于网络，如有侵权，请联系删除。