An Open-Label Extension Study to Evaluate the Long-Term Safety and Efficacy of Once Daily Mexiletine PR in Patients With Myotonic Dystrophy Type 1 and Type 2 Who Have Completed the MEX-DM-302 Study (ATLAS Study)

This is an open-label extension study intended to evaluate the long-term safety and efficacy of mexiletine PR in patients with myotonic dystrophy type 1 and type 2 (DM1 and DM2) who have completed the parent study MEX-DM-302.

开始日期2025-02-27

申办/合作机构

Lupin Ltd

[+1]

NCT06523400 / Not yet recruiting临床3期

A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Investigate the Efficacy and Safety of Once Daily Mexiletine PR During 26 Weeks of Treatment in Patients With Myotonic Dystrophy Type 1 and Type 2 (Phase 3)

A Randomized, Double-blind, Placebo-Controlled, Multi-Center Study to Investigate the Efficacy and Safety of Once Daily Mexiletine PR During 26 Weeks of Treatment in Patients with Myotonic Dystrophy Type 1 and Type 2 (HERCULES study)

开始日期2024-09-27

申办/合作机构

Lupin Ltd

[+1]

CTRI/2024/07/071462 / RecruitingN/A

An Open Label Balanced Randomized Single Dose One Treatment Fasting Vs Fed Two Sequence Fasting And Fed Two Period Two Way Crossover Oral Pharmacokinetics Study Comparing Mexiletine Hydrochloride Capsule 200 Mg Manufactured By Celogen Generics Pvt Ltd On Behalf Of Dawa Limited In Healthy Adult Human Male Subjects Under Fasting and Fed Conditions - Nil

开始日期2024-08-03

申办/合作机构

DAWA Ltd.

100 项与盐酸美西律相关的临床结果

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100 项与盐酸美西律相关的转化医学

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100 项与盐酸美西律相关的专利（医药）

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项与盐酸美西律相关的文献（医药）

2024-11-01·PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY

BK channels promote action potential repolarization in skeletal muscle but contribute little to myotonia

Article

作者: Blake, Brianna ; Rich, Mark M ; Dupont, Chris ; Voss, Andrew A

Abstract:

Patients with myotonia congenita suffer from slowed relaxation of muscle (myotonia), due to hyperexcitability caused by loss-of-function mutations in the ClC-1 chloride channel. A recent study suggested that block of large-conductance voltage- and Ca2+- activated K+ channels (BK) may be effective as therapy. The mechanism underlying efficacy was suggested to be lessening of the depolarizing effect of build-up of K+ in t-tubules of muscle during repetitive firing. BK channels are widely expressed in the nervous system and have been shown to play a central role in regulation of excitability, but their contribution to muscle excitability has not been determined. We performed intracellular recordings as well as force measurements in both wild type and BK−/− mouse extensor digitorum longus muscles. Action potential width was increased in BK−/− muscle due to slowing of repolarization, consistent with the possibility K+ build-up in t-tubules is lessened by block of BK channels in myotonic muscle. However, there was no difference in the severity of myotonia triggered by block of muscle Cl− channels with 9-anthracenecarboxylic acid (9AC) in wild type and BK−/− muscle fibers. Further study revealed no difference in the interspike membrane potential during repetitive firing suggesting there was no reduction in K+ build-up in t-tubules of BK−/− muscle. Force recordings following block of muscle Cl− channels demonstrated little reduction in myotonia in BK−/− muscle. In contrast, the current standard of care, mexiletine, significantly reduced myotonia. Our data suggest BK channels regulate muscle excitability, but are not an attractive target for therapy of myotonia.

2024-10-15·Journal of the American Heart Association

Defining Cardiomyocyte Repolarization Response to Pharmacotherapy in Long‐QT Syndrome Type 3

Article

作者: Ward, Deirdre ; Ge, Ning ; O'Brien, Stephen T. ; Galvin, Joseph ; Shen, Sanbing ; O'Brien, Timothy ; Xia, Wenxin ; Li, Rui ; McGorrian, Catherine ; McInerney, Veronica ; Prendiville, Terence W. ; Liu, Min

Background:

Long‐QT syndrome is a primary cardiac ion channelopathy predisposing a patient to ventricular arrhythmia through delayed repolarization on the resting ECG. We aimed to establish a patient‐specific, human induced pluripotent stem cell (hiPSC)‐derived cardiomyocytes model of long‐QT syndrome type 3 (LQT3) using clustered regularly interspaced palindromic repeats (CRISPR/Cas9), for disease modeling and drug challenge.

Methods and Results:

HiPSCs were generated from a patient with LQT3 harboring an SCN5A pathogenic variant (c.1231G>A; p.Val411Met), and an unrelated healthy control. The same SCN5A pathogenic variant was engineered into the background healthy control hiPSCs via CRISPR/Cas9 gene editing to generate a second disease model of LQT3 for comparison with an isogenic control. All 3 hiPSC lines were differentiated into cardiomyocytes. Both the patient‐derived LQT3 ( SCN5A+/− ) and genetically engineered LQT3 ( SCN5A+/− ) hiPSC‐derived cardiomyocytes showed significantly prolonged cardiomyocyte repolarization compared with the healthy control. Mexiletine, a cardiac voltage‐gated sodium channel (Na V 1.5) blocker, shortened repolarization in both patient‐derived LQT3 and genetically engineered LQT3 hiPSC‐derived cardiomyocytes, but had no effect in the control. Notably, calcium channel blockers nifedipine and verapamil showed a dose‐dependent shortening of repolarization, rescuing the phenotype. Additionally, therapeutic drugs known to prolong the corrected QT in humans (ondansetron, clarithromycin, and sotalol) demonstrated this effect in vitro, but the LQT3 clones were not more disproportionately affected compared with the control.

Conclusions:

We demonstrated that patient‐derived and genetically engineered LQT3 hiPSC‐derived cardiomyocytes faithfully recapitulate pathologic characteristics of LQT3. The clinical significance of such an in vitro model is in the exploration of novel therapeutic strategies, stratifying drug adverse reaction risk and potentially facilitating a more targeted, patient‐specific approach in high‐risk patients with LQT3.

2024-10-01·LANCET NEUROLOGY

Mexiletine versus lamotrigine in non-dystrophic myotonias: a randomised, double-blind, head-to-head, crossover, non-inferiority, phase 3 trial

Article

作者: Skorupinska, Iwona ; McDermott, Michael P ; Vivekanandam, Vinojini ; Hanna, Michael G ; Matthews, Emma ; Jayaseelan, Dipa L ; Barohn, Richard J

BACKGROUND:

Non-dystrophic myotonias are skeletal muscle channelopathies caused by ion channel dysfunction. Symptom onset is frequently in the first decade of life, causing disability in a young cohort. Although there is no cure, symptomatic treatments exist. Previous trials provide evidence of the efficacy of mexiletine. More recently, lamotrigine has been shown to be effective. Both treatments have different profiles, including pharmacokinetics and adverse events. This trial aimed to investigate whether lamotrigine is non-inferior to mexiletine to directly inform clinical practice.

METHODS:

We did a randomised, double-blind, crossover, non-inferiority, phase 3 trial at the National Hospital for Neurology and Neurosurgery (London, UK). Participants (aged ≥18 years) who had genetically confirmed symptomatic non-dystrophic myotonia were randomly assigned (1:1), by means of a block randomisation schedule created by a computer program, to receive either mexiletine for 8 weeks followed by lamotrigine for 8 weeks, or lamotrigine followed by mexiletine, with a 7-day washout period in between. Investigators and participants were masked to treatment allocation. The primary outcome measure was the mean interactive voice response (IVR) diary stiffness score (0-9 scale) over the participant's final 2 weeks of diary reporting in each treatment period. Non-inferiority was assessed using a mixed-effects model with a predefined margin of 0·5 and included all randomly assigned participants who contributed at least 7 days of IVR-diary data in either treatment period. The trial is registered at ClinicalTrials.gov, NCT05017155, and EudraCT, 2020-003375-17.

FINDINGS:

Between Aug 1, 2021, and Dec 12, 2022, of 60 participants were screened (24 females and 36 males) and randomly assigned between Aug 1, 2021 and Dec 12, 2022, to either the mexiletine-lamotrigine sequence (n=30) or the lamotrigine-mexiletine sequence (n=30). 53 participants contributed data to the primary analysis. The mean IVR stiffness score after treatment with mexiletine was 2·54 (95% CI 1·98 to 3·10) versus 2·77 (2·21 to 3·32) with lamotrigine (mean mexiletine-lamotrigine difference -0·23 [95% CI -0·63 to 0·17]). The most common adverse event with both treatments was indigestion-reflux (eight participants, 208 participant-days receiving mexiletine; seven participants, 130 participant-days receiving lamotrigine). No serious adverse events were reported.

INTERPRETATION:

We were unable to conclude that lamotrigine is non-inferior to mexiletine; however, improvements in all outcome measures from baseline were similar between lamotrigine and mexiletine. Lamotrigine is an important treatment consideration in non-dystrophic myotonias alongside mexiletine; we propose a treatment algorithm to guide clinical practice.

FUNDING:

Neuromuscular Study Group, Jon Moulton Charity Trust, UCLH BRC Fast Track Grant.

项与盐酸美西律相关的新闻（医药）

2023-11-06

·PRNewswire

Emerging Market Trends in Muscular Dystrophy: A DelveInsight Analysis of Becker Muscular Dystrophy, Myotonic Dystrophy, Facioscapulohumeral Muscular Dystrophy, and Limb-girdle Muscular Dystrophy

Muscular dystrophies are a group of genetic muscle disorders characterized by progressive muscle weakness. There are more than 40 different variations, and the most common ones in children are Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). LAS VEGAS, Nov. 6, 2023 /PRNewswire/ -- Muscular dystrophies encompass a range of muscle disorders resulting from genetic mutations. Over time, these conditions lead to muscle weakness, which hinders everyday activities. Muscular dystrophy takes various forms, each targeting specific muscle groups and manifesting at different ages with varying degrees of severity. It can either be hereditary or occur as a spontaneous genetic mutation. Additionally, there may be multiple genetic subtypes within each specific type of muscular dystrophy, and individuals with the same subtype may exhibit varying symptoms. DelveInsight has recently released a series of epidemiology-based market reports focusing on muscular dystrophy including Becker Muscular Dystrophy, Myotonic Dystrophy, Facioscapulohumeral Muscular Dystrophy, and Limb-girdle Muscular Dystrophy. These reports include a comprehensive understanding of current treatment practices, historical and forecasted patient pool, emerging drugs, market share of individual therapies, and historical and forecasted market size from 2019 to 2032 segmented into 7MM [the United States, the EU-4 (Italy, Spain, France, and Germany), the United Kingdom, and Japan]. Additionally, the reports feature exhaustive analysis of prominent companies working with their emerging candidates in different stages of clinical development. Let's deep dive into the assessment of these muscular dystrophy reports market individually. Becker Muscular Dystrophy Market Becker muscular dystrophy (BMD) is a genetic disorder that primarily impacts muscle structure. It leads to the gradual deterioration of limb, cardiac, and skeletal muscles. Interestingly, involuntary muscles remain unaffected. BMD is considered a milder form of Duchenne muscular dystrophy (DMD). Typically, BMD manifests in one's teenage years or early adulthood, and its progression is slower and less predictable compared to DMD. As per DelveInsight analysis, it can be observed that prevalence of BMD is high in the 7MM, and similarly, high rate of treatment is seen in patients. The approach to BMD treatment centers on symptom management since there is no definitive cure available. Instead, there are treatments designed to alleviate symptoms and enhance muscle functionality. It's essential for individuals living with BMD to maintain their physical conditioning and muscle usage. While there are no FDA-approved drugs specifically for BMD, researchers are actively investigating various therapeutic interventions. As per DelveInsight analysis, the dynamics of the becker muscular dystrophy market are anticipated to change in the coming years owing to the positive outcomes of the emerging pipeline candidates during the developmental stage by key players that are under phase III, II and I clinical development have the potential to create a significant positive shift in BMD market size. Becker Muscular Dystrophy Pipeline Therapies and Companies EDG-5506: Edgewise Therapeutics, Inc./Medpace, Inc. Vamorolone: ReveraGen BioPharma, Inc./Santhera Pharmaceuticals For a comprehensive view of the Becker muscular dystrophy market, check out the Becker Muscular Dystrophy Market Assessment Myotonic Dystrophy Market Myotonic dystrophy, an umbrella term for two rare genetic disorders with autosomal dominant inheritance patterns, impacts various bodily systems, featuring a clinical triad of progressive muscle weakness, myotonia, and early-onset cataracts. These disorders are classified into two primary types: DM type 1 (DM1) and DM type 2 (DM2). DelveInsight estimated that the total diagnosed prevalent patient population of myotonic dystrophy in the 7MM countries was close to 80K cases in 2021. As per the estimates, the US had the highest patient population of myotonic dystrophy in 2021. Although numerous pre-clinical advancements have been made, there is currently no targeted disease-modifying treatment available. The mainstay of management primarily involves monitoring for complications and adhering to standard care practices, such as utilizing assistive devices, administering hormone therapy, and providing pain relief. Several clinical studies have systematically assessed the efficacy of therapeutic agents in managing the condition. However, the scarcity of scientific evidence, coupled with the complex and diverse manifestations of the disease, poses significant challenges for healthcare providers when it comes to identifying and selecting appropriate medications. To tap the uncovered myotonic dystrophy market, few players have targeted the unmet need fortreatment. As per DelveInsight analysis, the myotonic dystrophy market is expected to grow from USD 80 million in 2021 at a significant CAGR by 2032. The current pipeline consists of both mid and late-stage candidates. The few promising therapies inthe mid and late-stage development are expected to experience significant reconstitution during the forecastperiod. Hence, more research and studies are needed to develop potential therapies that cater to the unmet need for curative and disease-modifying therapy in myotonic dystrophy patients. Myotonic Dystrophy Pipeline Therapies and Companies AMO-02 (tideglusib): AMO Pharma Limited Mexiletine: Lupin Ltd. Pitolisant: Harmony Biosciences, LLC AOC 1001: Avidity Biosciences, Inc. DYNE-101: Dyne Therapeutics To gain a deeper understanding of the myotonic dystrophy market, be sure to explore the Myotonic Dystrophya Market Outlook Facioscapulohumeral Muscular Dystrophy (FSHD) Market Facioscapulohumeral muscular dystrophy (FSHD), a genetically inherited disorder, progressively weakens muscles and significantly reduces the functional capacity of those affected. Recent years have witnessed substantial progress in our understanding of how epigenetic factors play a role in this condition. FSHD can be categorized into two subtypes based on the mechanisms of reduced methylation and failed epigenetic repression. Type 1 accounts for approximately 95% of FSHD cases and is characterized by the loss of D4Z4 repeats. The remaining 5% fall into Type 2, where methylation and epigenetic changes occur independently of deletions. Regardless of the subtype, FSHD leads to the same outcome. As per DelveInsight analysis, in the year 2021, the total prevalent cases of FSHD were 78K in the 7MM which are expected to grow during the study period, i.e., 2019–2032. As of now, there are no officially approved therapies for managing FSHD. However, individuals dealing with FSHD can find relief by utilizing orthotic devices designed to support their feet. These devices are particularly effective in addressing common FSHD symptoms like foot drop and shoulder weakness. Depending on the degree of foot drop, a custom-made ankle-foot orthosis (AFO) can provide significant benefits. In cases where knee extensor weakness may worsen gait with an AFO, alternatives like floor reaction ankle-foot orthosis (FRAFO) or advanced knee-ankle-foot orthosis (KAFO) may be considered. Regular exercise, especially hydrotherapy, plays a crucial role in preserving mobility and pain management. Additionally, weight management, potentially through dietary adjustments, is essential to reduce strain on already weakened muscles. It's important to note that there is currently no cure for FSHD, but there are treatments and devices available to alleviate many of its symptoms. Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed to enhance comfort and mobility. According to DelveInsight, the FSHD market in 7MM is expected to witness a major change in the study period (2019–2032). As per estimates, in 2021, the total FSHD market size was USD 25.55 million which is expected to rise by 2032. This increase in market size is mainly due to extensive research and development activities of pharmaceutical companies, along with the expected launch of approved therapies. Facioscapulohumeral Muscular Dystrophy Pipeline Therapies and Companies Losmapimod: Fulcrum Therapeutics/GSK GYM329 (RO7204239/RG 6237): Roche Explore in-depth for a comprehensive understanding of the FSHD Clinical Trials Limb-girdle Muscular Dystrophy Market Limb-girdle muscular dystrophies (LGMD), also known as pelvofemoral muscular dystrophy or proximal muscular dystrophy, encompass a group of infrequent genetic disorders characterized by the progressive wasting and weakening of voluntary muscles located in the hip and shoulder regions. This muscle weakness and atrophy gradually advance and can eventually impact other muscle groups in the body. As per data from the National Organization for Rare Disorders, LGMD affects both males and females in roughly equal proportions. The exact prevalence of LGMD remains uncertain, but estimates suggest a range between one in 14,500 to one in 123,000 individuals. It's important to note that the age at which symptoms manifest can vary significantly, even within the same family. Additionally, the relative frequencies of the different LGMD types differ across populations, though it is worth mentioning that LGMD2G, 2H, and 2J are exceedingly rare on a global scale. Currently, there is no known cure for LGMD. However, there are supportive therapies designed to manage and alleviate its symptoms. The approach to LGMD management is individualized, focusing on addressing specific symptoms that each patient experiences. Treatment options may involve physical and occupational therapy to enhance muscle strength and prevent contractures, the utilization of assistive devices like canes, braces, walkers, or wheelchairs to aid mobility, corrective surgery for skeletal issues like scoliosis, and regular monitoring of cardiac and respiratory health for potential complications associated with certain LGMD subtypes. According to DelveInsight's' estimates, the limb girdle muscular dystrophy market in 7MM is expected to show a positive growth, during the forecast period (2023–2032), mainly attributed to anticipated launch of emerging therapy and the increasing cases of LGMD. Limb-girdle Muscular Dystrophy Pipeline Therapies and Companies SRP-6004: Sarepta Therapeutics, Inc. LION-101: Asklepios Biopharmaceutical, Inc. BBP-418 (ribitol): ML Bio Solutions, Inc. To access a complete analysis of the limb-girdle muscular dystrophy market, visit Limb-girdle Muscular Dystrophy Market Assessment Trending Genetic Disorders Reports Duchenne Muscular Dystrophy Market Duchenne Muscular Dystrophy Market Insights, Epidemiology, and Market Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key DMD companies, including Pfizer, Santhera Pharmaceuticals, ReveraGen BioPharma, Taiho Pharmaceutical, FibroGen, Sarepta Therapeutics, Capricor Therapeutics, Daiichi Sankyo, Italfarmaco, Antisense Therapeutics, Solid Biosciences, among others. Alpha-1 Antitrypsin Deficiency Market Alpha-1 Antitrypsin Deficiency Market Insights, Epidemiology, and Market Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key A1ATD companies, including Arrow Head Pharmaceuticals, Mereo Biopharma, Kamada Ltd, Grifols, CSL Behring, Shire, LFB Biotechnologies, among others. Wilson Disease Market Wilson Disease Market Insights, Epidemiology, and Market Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key Wilson disease companies, including Orphalan, AstraZeneca, Vivet Therapeutics, Pfizer, Ultragenyx Pharmaceutical, among others. Cystic Fibrosis Market Cystic Fibrosis Market Insights, Epidemiology, and Market Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key cystic fibrosis companies, including Verona Pharmaceuticals, Eloxx Pharmaceuticals, Inc., Santhera Pharmaceuticals, Laurent Pharmaceuticals Inc., Vertex Pharmaceuticals, among others. About DelveInsight DelveInsight is a leading healthcare-focused market research and consulting firm that provides clients with high-quality market intelligence and analysis to support informed business decisions. With a team of experienced industry experts and a deep understanding of the life sciences and healthcare sectors, we offer customized research solutions and insights to clients across the globe. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +1(919)321-6187 Logo: SOURCE DelveInsight Business Research, LLP

临床3期

2022-09-30

·佰傲谷BioValley

里程碑！首个渐冻症（ALS）生存改善药物获FDA批准上市

近日（2022年9月29日），FDA批准了Amylyx的AMX0035的新药上市申请，用以治疗肌萎缩侧索硬化症（ALS），商品名为Relyvrio。AMX0035的批准成为首个改善ALS功能和生存的新药。半年的生存获益 ALS是个高度致死疾病，发病机理未知，90%的ALS为偶发性。在Relyvrio之前，被获批使用的Rilutek、Tiglutik、 Mexiletine等均为延缓病情用药，未有任何改善疗法。 AMX0035是一种由苯丁酸钠（PB）和牛磺熊去氧胆酸（TUDCA）组成的组合药物。在此前的试验中显示，Amylyx制药公司发现这两种化合物按特定比例服用时具有协同作用，AMX0035有望通过同时抑制内质网和线粒体应激反应阻止神经元死亡和神经炎症。2017年，AMX0035获得FDA授予的罕见病药物称号。获批是基于一项名为CENTAUR的临床试验数据，该临床试验共计入组了137名ALS受试者，患者按2：1的比例被随机分配分别接受AMX0035或安慰剂治疗。试验结果显示，与安慰剂组相比，AMX0035治疗组的死亡风险降低了44%。试验开始就使用AMX0035治疗组的中位生存时间为25.0个月，最初安慰剂组为18.5个月。治疗组平均获得了多了长达6.5个月的生存获益。哈佛医学院的神经病学教授Julieanne Dorn表示：”这是第一个在患者功能和生存期方面都显示出显著临床获益的临床研究“。基于该临床数据，Amylyx已于6月获加拿大批准使用。上市一波三折对于ALS患者而言，AMX0035的批准过程也十分曲折。即便AMX0035相比ALS以往批准用药，在改善ALS患者功能和生存期的改善上表现了积极意义。但仍有专家对AMX0035的治疗效果表示质疑。指出AMX0035的治疗效果并不显著，只有50%服用AMX0035的患者能活到两年时间。且在对呼吸、住院率以及整体肌肉力量等指标测试中，AMX0035的表现并未优于安慰剂。因此一开始，FDA以及FDA专家会都未对AMX0035持看好态度。在准备递交在美的上市申请时，FDA就向Amylyx表示（2021年4月）希望看到更多数据。在Amylyx补充额外的安慰剂对照研究数据之前，不能提交AMX0035上市申请。在今年3月的FDA外周和中枢神经系统药物咨询委员会上，AMX0035被以6（反对）：4（支持）投票结果反对批准上市。之后，Amylyx公司递交了进一步数据分析及及来自其它临床试验的支持数据。在两周前的第二次咨询委员会上，Amylyx又获得了7（赞成）：2（反对）的投票支持。总结对于任何一款可能改善ALS的新药，ALS患者群体抱有殷切希望，此前FDA在拒绝批准一款ALS干细胞疗法时候，就遭到了美国渐冻症患者团体等强烈谴责。而对于AMX0035的批准，ALS群体同样表达了期盼。此前FDA在批准AMX003犹豫不决时，也受到了ALS协会催促，呼吁其尽快批准AMX0035，以使ALS病人尽快获得可能有益的治疗。内容来源于网络，如有侵权，请联系删除。

上市批准

2022-07-02

·丁香园

急诊遇室速不再慌，我们整理了 2 张流程图！

室性心动过速是临床常见心律失常，该如何正确识别和治疗？今天帮大家梳理一下。室速的识别室性心动过速：简称室速，是起源于希氏束分支以下的特殊传导系统或者心室肌的连续 3 个或 3 个以上的异位心搏。及时正确的判断和治疗室速具有非常重要的临床意义。室速的心电图特征对于识别室速非常重要：1） 3 个或以上的室性期前收缩连续出现；2） QRS 波形态畸形，时限超过 0.12 s，ST-T 波方向与 QRS 波主波方向相反；3）心室率通常为 100～250 次/分，心律规则，但亦可略不规则；4）心房独立活动与 QRS 波无固定关系，形成室房分离，偶尔个别或所有心室激动逆传夺获心房；5）通常发作突然开始；6）心室夺获与室性融合波。室速与室上性心动过速伴室内差异性传导的心电图易混淆。以下支持室上性心动过速伴室内差异性传导：1）每次心动过速均有期前发生的 P 波开始；2） P 波与 QRS 波相关，通常 1:1 房室比例；3）刺激迷走神经可减慢或终止心动过速；此外心动过速未应用药物前 QRS 时限超过 200 ms、宽窄不一、心律明显不规则、心率超过 200 次/分，应怀疑为预激综合征合并心房颤动。图. WPW 综合征合并房颤（来源参考文献 2）节律绝对不规则，QRS 宽大，心动过速；房颤波取如下之道传至心室：a. 经 AV 结和附加通道同时传导产生宽大 QRS 波 b. 或只经 AV 下传，QRS 不增宽（无预激波）c. 或只经附加通道下传，产生宽大预激波；如心率很快，高度室颤风险以下支持室速：1）室性融合波；2）心室夺获；3）房室分离；4）全部心前区导联 QRS 波主波方向呈同向性，即全部向上或向下。图. 室性心动过速伴不完全房室分离，夺获及融合波（来源参考文献 2）约 50% 之室速伴房室分离，心房冲动传入心室，或与心室异位搏动融合（F），或完全夺获心室（C），如梯形图所示特殊类型室速：1）加速性心室自主节律（accelerated idioventricular rhythm）：亦称缓慢型室速。心率通常为 60～100 次/分，心动过速开始与终止呈渐进性，由于心室与窦房结两个起搏点轮流控制节律，融合波常出现于心律失常的开始与终止时，心室夺获也很常见。本型室速通常发生于急性心肌梗死再灌注期间、心脏手术、心肌病、风湿热与洋地黄中毒。患者一般无症状也不影响预后，通常无需抗心律失常治疗。图. 加速性室性自主节律（来源参考文献 2）AV 分离，QRS > 0.12 s，速率 85/min，R-R 基本规则2）尖端扭转型室速（torsades de pointes）：发作时 QRS 波振幅与波峰呈周期性改变，呈扭转样，频率 200～250 次/分。其他特征包括 QT 间期通常＞ 0.5 s，U 波显著。可发展为室颤和猝死。病因分为先天性和获得性。先天性包括：多种编码钠、钾离子通道的基因突变。获得性包括：药源性（IA 类或 III 类抗心律失常药物、三环类抗抑郁药、大环内酯类抗生素、抗组胺药、抗肿瘤药物、乌头碱等）、心源性（心动过缓伴长间歇）、神经源性（颅内病变）及代谢性（电解质紊乱，如低钾血症、低镁血症）等。图. 扭转型室速（来源参考文献 2）注意 QRS 扭上扭下，T 波圆钝，频率亦不一，室颤频率常为 300～500/min，而 TdP 较慢室速的治疗一、非持续性室速非持续性室速（non-sustained ventricular tachycardia，NSVT）指连续 3 个及 3 个以上的室性心律，频率 > 100 次/min，持续时间 < 30 s，能够自行终止，且不会引起明显的血流动力学改变。治疗1）心脏结构正常的 NSVT：大多数 NSVT 患者只有当出现症状、频繁发作或引发心功能不全时才就诊。药物治疗包括 β 受体阻滞剂、非二氢吡啶类钙通道阻滞剂、Ⅰc 类抗心律失常药物如普罗帕酮。药物无效或不能耐受者, 可行导管消融治疗，成功率较高。2）结构性心脏病的 NSVT：对于伴有结构性心脏病的 NSVT 患者，治疗基础心脏病较治疗心律失常本身更为重要。必要时可行电生理检查，甚至安装植入型心律转复除颤器（ICD）。NSVT：非持续性室性心动过速；LVEF：左心室射血分数；CPVT：儿茶酚胺敏感性多形性室性心动过速；LQTS：长 QT 综合征；室速：室性心动过速；室颤：心室颤动；ICD：植入型心律转复除颤器二、持续性单形性室速持续性单形性室速（sustained monomorphic ventricular tachycardia，SMVT）持续时间 ≥ 30 s，或持续时间虽 < 30 s 但室速发作时伴随血流动力学障碍需早期进行干预者称为 SMVT。SMVT 大多发生于结构性心脏病患者，但也可见于目前的诊断技术尚不能发现的心脏病患者，后者被称为特发性室速。治疗1）特发性 SMVT 治疗的适应证主要取决于患者的症状负荷。β 受体阻滞剂和非二氢吡啶类钙通道阻滞剂疗效中等且风险小，可以首选，尤其适用于对维拉帕米敏感的特发性室速患者。索他洛尔、美西律、普罗帕酮、胺碘酮等抗心律失常药疗效虽更好，但不良反应及致心律失常风险相对较高。导管消融治疗局灶性右心室流出道室速的成功率高，且操作风险低；起源于左心室流出道和左后分支型室速如若药物治疗效果不好，也可考虑行导管消融治疗。2）结构性心脏病患者应用抗心律失常药物后发生致心律失常作用的风险增加，因此临床上常将其作为植入 ICD 后的辅助治疗。索他洛尔可以降低结构性心脏病患者 SMVT 的复发率，安全性与单用美托洛尔相当。只要基线 QT 间期或肾功能正常，索他洛尔就可作为抑制 SMVT 复发的首选药物。与单用美托洛尔相比，胺碘酮作为二级预防药物 1 年内的治疗效果较好，但长期应用效果尚不明确。三、持续性多形性室速（polymorphic ventricular tachycardia，PMVT）PMVT 指 QRS 波形态可清楚识别但连续发生变化、频率 > 100 次/min，持续时间 ≥ 30 s，或虽然 < 30 s 但患者血流动力学不稳定需立即终止的室性心律失常。PMVT 易蜕变为室扑或室颤。治疗1）治疗基础心脏病，纠正诱因。2）ICD 是不可逆性原因所致 PMVT 患者的主要治疗措施。对于有可能在短时间内再发 PMVT 且暂不适合植入 ICD 的患者，可考虑穿戴式心律转复除颤器（wearable cardioverter-defibrillator，WCD）治疗。3）抗心律失常药物治疗：β 受体阻滞剂、胺碘酮和（或）利多卡因。4）由室早触发的 PMVT 患者，可考虑导管消融治疗。5）自主神经系统干预，降低心脏交感神经张力，进而达到抗心律失常作用。室速：室性心动过速；ACLS：高级心血管生命支持；ACS：急性冠状动脉综合征；SHD：结构性心脏病；WCD：穿戴式心律转复除颤器；LVEF：左心室射血分数；ICD：植入型心律转复除颤器室速的急诊处置1）识别和纠正血流动力学障碍。2）基础疾病和诱因的纠正与处理。3）衡量获益与风险，对于致命性室性心律失常，应立即采用药物或非药物治疗措施终止其发作；对于非致命性室性心律失常，需更多考虑治疗措施的安全性。4）治疗与预防兼顾。5）抗心律失常药物的急诊应用原则：根据基础心脏疾病、心功能状态选择抗心律失常药物。若静脉应用抗心律失常药物疗效不满意，应评估选用的药物是否恰当、剂量是否达标。不建议短期内换用或合用另外一种抗心律失常药物。联合应用的原则为单用一种抗心律失常药物无效时，考虑加用另外一种作用机制不同的药物。SMVT：对于血流动力学不稳定的 SMVT 需立即电复律，血流动力学稳定者应根据有或无结构性心脏病制定治疗策略。要终止血流动力学稳定的 SMVT 可首选抗心律失常药，也可电复律和导管消融。PMVT：对于血流动力学不稳定的 PMVT，应立即电复律或电除颤。如果血流动力学稳定，根据 QT 间期的不同，其处理策略也相应改变。1）伴 QT 间期延长的 PMVT多为 TdP，常表现为反复发作的阿斯综合征，严重者可发生 SCD。心电图显示 QT 间期延长（获得性和先天性）。① 获得性 QT 间期延长伴 TdP- 首先寻找并停用一切可引起 QT 间期延长的药物或纠正相关因素。- 硫酸镁缓慢静脉注射用于发作频繁且不易自行转复者，静脉输注直至 TdP 发作明显减少和 QT 间期缩短至 500 ms 以内。- 积极补钾，将血钾维持在 4.5～5.0 mmol/L。- 与心动过缓相关的 TdP，予以临时起搏治疗。行临时起搏治疗前，异丙肾上腺素可用于提高心室率，但不适用于先天性 LQTS 或冠心病患者；阿托品也可试用于提高心室率的治疗。- 部分获得性 LQTS 合并 TdP 的患者可能存在潜在遗传基因异常，上述治疗措施无效时，在临时起搏基础上可考虑 β 受体阻滞剂或利多卡因治疗。- 不推荐使用其他抗心律失常药物。② 先天性 QT 间期延长伴 TdP- 纠正电解质紊乱。- β 受体阻滞剂可作为首选，急性期即可开始应用。可使用非选择性的 β 受体阻滞剂普萘洛尔，也可选择其他制剂。通常所需剂量较大，应用至患者可耐受的最大剂量（静息心率维持在 50～60 次/min）。- 美西律对 LQT3 可能有效。2）QT 间期正常的 PMVT- 积极纠正病因和诱因；- 对偶尔出现的无严重血流动力学障碍的非持续性发作者，可观察或给予 β 受体阻滞剂治疗, 一般不需静脉给予抗心律失常药物；- 对于持续发作或反复发作者，可静脉应用 β 受体阻滞剂、胺碘酮、尼非卡兰或利多卡因。编辑：ly投稿：wangliya1@dxy.cn题图来源：站酷海洛参考文献：[1] 葛均波, 徐永健. 内科学. 第 8 版 [M]. 人民卫生出版社, 2013.[2] 蔡伯林. 实用心电图图谱 [M]. 人民军医出版社, 2011.[3] 曹克将, 陈明龙, 江洪, 等. 室性心律失常中国专家共识 [J]. 中国心脏起搏与心电生理杂志, 2016.[4] 中华医学会心电生理和起搏分会, 中国医师协会心律学专业委员会. 2020 室性心律失常中国专家共识 (2016 共识升级版)[J]. 中华心律失常学杂志, 2020, 24(3):71.‍‍‍‍‍‍

100 项与盐酸美西律相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D00639	盐酸美西律	C01BB02	DB00379

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
非营养不良性肌强直综合征	欧盟	Lupin Ltd	2018-12-18
非营养不良性肌强直综合征	冰岛	Lupin Ltd	2018-12-18
非营养不良性肌强直综合征	列支敦士登	Lupin Ltd	2018-12-18
非营养不良性肌强直综合征	挪威	Lupin Ltd	2018-12-18
肺脓肿	日本	Chemix, Inc.	2005-07-08
腹膜炎	日本	Chemix, Inc.	2005-07-08
肺炎	日本	Chemix, Inc.	2005-07-08
心律失常	日本	Taiyo Pharma Co., Ltd.	1985-01-31
糖尿病性神经病变	日本	Taiyo Pharma Co., Ltd.	1985-01-31

未上市

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
肌强直性营养不良	临床3期	法国	Lupin Ltd	2021-09-03
肌强直性营养不良	临床3期	-	Lupin Ltd	2021-09-03
HIV感染	临床2期	美国	Boehringer Ingelheim GmbH	2001-08-31
HIV感染	临床2期	坦桑尼亚	Boehringer Ingelheim GmbH	2001-08-31
痛性神经病变	临床2期	美国	Boehringer Ingelheim GmbH	2001-08-31
痛性神经病变	临床2期	坦桑尼亚	Boehringer Ingelheim GmbH	2001-08-31

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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


MDS2023	N/A	肌强直	183	Mexiletine	繭範齋鬱窪醖淵範鏇糧(鏇網蓋齋憲鑰壓艱憲遞) = mexiletine significantly causes some GIT symptoms compared to placebo (RR 3.7, 95% CI [1.79 to 7.64]) 淵齋鬱糧膚選簾鑰醖網 (積夢廠鑰獵願蓋糧膚夢 )	积极	2023-08-27
ESC2020	N/A	QT间期延长综合征2	20	mexiletine	範鹹齋糧觸遞網願繭積(鏇繭鬱網願積憲觸鑰積) = 範夢廠獵繭膚壓鑰積衊齋襯廠簾鑰餘齋壓選鬱 (衊構壓觸膚鏇憲憲衊製 )	-	2020-08-28
2531 (AAN2020)	临床2期	肌萎缩侧索硬化	20	Placebo	願遞窪衊艱廠製憲製淵(網夢廠願餘簾積鏇齋憲) = 壓鹹遞窪鹽蓋壓構鹽鹹繭範齋艱遞襯艱鹽窪遞 (夢製襯艱廠範鑰遞膚鬱, 2.2) 更多	积极	2020-04-14
				Mexiletine 300 mg	憲鹽齋夢製夢鬱壓網鹹(糧觸鬱願壓選膚網遞窪) = 膚選壓選艱鏇廠醖夢憲襯願壓鬱範觸鹽繭願鹽 (夢廠繭夢壓鬱蓋艱鹹製, 0.315 ~ 1.102)
NCT02781454 (Mexiletine-2, CTgov)	临床2期	肌萎缩侧索硬化	20	Mexiletine (Mexiletine, 300 Milligrams)	淵衊艱鹽獵窪鑰窪糧夢(範顧鹹選憲膚鬱顧築願) = 願築簾憲構觸網餘憲淵餘獵願鹽獵築顧膚醖簾 (遞鹹壓構鏇選蓋淵觸糧, 夢構築範鹹襯夢糧積選 ~ 獵簾壓衊鏇醖鹽積遞壓) 更多	-	2019-12-05
				Mexiletine (Mexiletine, 600 Milligrams)	淵衊艱鹽獵窪鑰窪糧夢(範顧鹹選憲膚鬱顧築願) = 鬱範齋遞觸壓製齋廠齋餘獵願鹽獵築顧膚醖簾 (遞鹹壓構鏇選蓋淵觸糧, 積獵餘構憲鹹積衊餘膚 ~ 鑰鹽夢鏇糧築製壓夢窪) 更多
WCN2019	N/A	非营养不良性肌强直综合征	-	Safinamide	簾蓋鏇鹽壓壓蓋憲餘獵(觸襯簾夢網鏇觸製範構) = 廠餘窪夢鑰獵醖鹽鹽膚繭壓遞廠觸窪淵壓壓築 (艱蓋醖淵壓構鬱廠壓範 ) 更多	-	2019-10-15
				Mexiletine	簾蓋鏇鹽壓壓蓋憲餘獵(觸襯簾夢網鏇觸製範構) = 繭醖範窪築範築廠鹽鏇繭壓遞廠觸窪淵壓壓築 (艱蓋醖淵壓構鬱廠壓範 ) 更多
NCT02260388 (PAIN-CONTRoLS, CTgov)	临床4期	疼痛 \| 感觉性多发性神经病 \| 神经病	402	Nortriptyline (Nortriptyline)	網觸願積夢鬱簾鹽網積(獵選鏇遞鏇憲顧糧遞襯) = 膚衊獵選築窪艱獵獵艱鏇餘鹹糧憲鏇鑰艱顧簾 (顧願鑰醖鹹願簾鹹觸憲, 遞壓願鹹糧壓襯衊鹽醖 ~ 繭鏇衊鬱壓齋齋艱膚廠) 更多	-	2018-07-06
				Duloxetine (Duloxetine)	網觸願積夢鬱簾鹽網積(獵選鏇遞鏇憲顧糧遞襯) = 觸觸淵淵窪鏇膚遞糧製鏇餘鹹糧憲鏇鑰艱顧簾 (顧願鑰醖鹹願簾鹹觸憲, 鏇膚齋齋壓廠鬱選選遞 ~ 鬱齋淵願鏇窪鑰鹹糧鬱) 更多
AAN2018	N/A	非营养不良性肌强直综合征	30	Mexiletine	構鹽齋觸襯膚構鬱鹽願(醖廠網願襯蓋構廠鑰艱) = 遞顧齋繭醖鑰選構鬱襯構觸鑰夢鬱廠淵選蓋簾 (醖淵構鹽鹽憲醖範遞簾 ) 更多	积极	2018-04-10
NCT01406873 (CTgov)	临床2期	肌强直性营养不良	42	Mexiletine	憲遞壓醖糧膚選繭鑰夢(憲築構遞膚觸獵繭構鏇) = 鏇窪積衊艱艱膚繭選願遞鏇積顧遞餘夢餘築積 (淵齋襯鹽範簾鏇範觸顧, 夢鹹廠網積鏇鹽構廠範 ~ 膚積獵醖簾艱鏇淵網願) 更多	-	2018-03-29
NCT01811355 (CTgov)	临床4期	肌痛性痉挛 \| 肌萎缩侧索硬化	23	Mexiletine (Mexiletine)	築衊齋遞鹹鏇蓋鬱顧獵(餘襯網網鑰築構艱衊憲) = 糧範膚淵鬱膚願蓋糧繭淵襯鑰繭糧選壓齋壓糧 (襯選醖製築觸簾壓選憲, 網餘膚齋餘醖網蓋構繭 ~ 壓蓋製齋顧鬱醖鹽遞繭) 更多	-	2017-06-27
				Placebo (Placebo)	築衊齋遞鹹鏇蓋鬱顧獵(餘襯網網鑰築構艱衊憲) = 遞構鏇積鹹餘繭願襯遞淵襯鑰繭糧選壓齋壓糧 (襯選醖製築觸簾壓選憲, 顧選襯築鑰鹽觸鹽廠窪 ~ 憲積顧構願鑰顧遞製願) 更多
S38.004 (AAN2017)	N/A	肌痛性痉挛	20	Mexiletine 150mg BID	築鹹淵襯淵鏇遞壓顧構(膚範選積壓衊顧壓簾築) = 憲鑰積淵顧網鑰壓鏇顧齋鑰願遞壓獵鹹膚鏇獵 (衊憲鹽繭糧積選廠蓋憲 ) 更多	积极	2017-04-18