预约演示

更新于：2025-05-16

Clemastine Fumarate

富马酸氯马斯汀

更新于：2025-05-16

概要

基本信息

药物类型

小分子化药

别名

(+)-(2R)-2-(2-(((R)-p-chloro-α-methyl-α-phenylbenzyl)oxy)ethyl)-1-methylpyrrolidine、(+)-(2R)-2-[2-[[(R)-p-chloro-α-methyl-α-phenylbenzyl]oxy]ethyl]-1-methylpyrrolidine、Clemastine

+ [9]

靶点

H1 receptor

作用方式

拮抗剂

作用机制

H1 receptor拮抗剂(组胺H1受体拮抗剂)

治疗领域

在研适应症

非在研适应症

原研机构

在研机构

山东科源制药股份有限公司NISSIN Pharmaceutical Co., Ltd.

非在研机构

Novartis Pharmaceuticals Corp.

NovaDel Pharma, Inc.

权益机构-

最高研发阶段批准上市

首次获批日期

日本 (1970-01-17),

普通感冒皮炎湿疹+ [3]

最高研发阶段(中国)批准上市

特殊审评-

登录后查看时间轴

结构/序列

分子式C25H30ClNO5

InChIKeyPMGQWSIVQFOFOQ-YKVZVUFRSA-N

CAS号14976-57-9

关联

项与富马酸氯马斯汀相关的临床试验

NCT06591091

/ Not yet recruiting临床2期IIT

Clemastine for Improving White Matter and Boosting Antidepressant Response in Late-life Depression

The goal of this study is to find out if the antihistamine, clemastine, can make the white matter in the brain better in older adults with depression. The study will also determine whether this improvement can make antidepressant treatment work better, reduce depressive symptoms, and improve memory and thinking.

开始日期2025-04-01

申办/合作机构

University of Illinois

[+1]

NCT06065670

/ Not yet recruiting临床1/2期IIT

A Randomized, Double-Blind, Delayed Treatment, Placebo-Controlled Trial to Assess the Changes in Multi-parametric MRI in Patients With Acute Demyelinating Lesions Taking Clemastine Fumarate as a Myelin Repair Therapy

The clinical trial is intended to assess for clinical evidence of Clemastine Fumarate as a myelin repair therapy in patients with acute inflammatory injury-causing demyelination as measured by multi-parametric MRI assessments.
No reparative therapies exist for the treatment of acute demyelinating lesions. Clemastine fumarate was identified along with a series of other antimuscarinic medications as a potential remyelinating agent using the micropillar screen (BIMA) developed at the University of California, San Francisco (UCSF). Following in vivo validation, an FDA IND exemption was granted to investigate clemastine for the treatment of multiple sclerosis in the context of chronic optic neuropathy. That pilot study was recently completed and is the first randomized control trial documenting efficacy for a putative remyelinating agent for the treatment of MS. The preselected primary efficacy endpoint (visual evoked potential) was met and a strong trend to benefit was seen for the principal secondary endpoint assessing function (low contrast visual acuity). That trial number was 13-11577.
This study seeks to follow up on that study and examine clemastine fumarate's protective and reparative effects in the context of acute demyelinating brain lesions as imaged by multi-parametric MRI assessments. The investigators will be assessing the effects of clemastine fumarate as a remyelinating therapy and assessing its effect on MRI metrics of lesions found in patients with a confirmed diagnosis of acute inflammatory injury-causing demyelination.
In addition to using conventional multi-parametric MRI assessments, this study will also evaluate a new MRI technique called Ultrashort Echo Time (UTE) MRI to assess the effects of clemastine fumarate as a remyelinating therapy of acute lesions found in patients with a confirmed diagnosis of acute inflammatory injury-causing demyelination and compare it to the other assessments.

开始日期2024-09-15

申办/合作机构

The University of California, San Francisco

NCT06315972

/ Not yet recruiting临床2期IIT

Combining Clemastine and Aerobic Exercise to Treat Cognitive Dysfunction in Schizophrenia by Targeting Myelin Plasticity

Schizophrenia (SZ) is a broad clinical entity characterized by different subjective symptoms,behavioural signs, and disease course. Research has pointed to numerous biological indicators tentatively associated with neurocognitive dysfunction, brain structural and neurochemical alterations. Cognitive deficits occur as early as the prodromal phase of the illness and significantly determine its outcome. Pathophysiologically, SZ is regarded as a disconnectome disorder in which frontal and temporal brain regions are functionally disconnected, which contributes substantially to the development of cognitive dysfunction.
Impaired connectivity is related to synaptic (microconnectivity) and myelin (macroconnectivity) plasticity. With design-based stereology, a decreased number of oligodendrocytes (OLs) in the CA4 hippocampal subregion as the basis for disturbed myelination and impaired cognition, but also a decrease in the prefrontal cortex were observed. Animal studies demonstrated that clemastine enhances remyelination by increasing the differentiation of oligodendrocyte precursor cells (OPCs) and showed that aerobic exercise increases the rate of remyelination and proliferation of OPCs; this clinically meaningful effect of aerobic exercise is stronger in combination with clemastine. Furthermore, aerobic exercise improves everyday functioning, measured by the Global Assessment of Functioning (GAF) scale, and cognitive dysfunction in SZ and increases hippocampal volume, especially the volume in the hippocampal CA4 subregion. This regional volume change correlates negatively with global and cell-specific polygenic risk scores (PRSs), indicating that OPCs are involved in the genetic risk mechanisms and disturbed plasticity underlying SZ. In patients with multiple sclerosis, 90 days' administration of clemastine fumarate 10.72 mg/day, corresponding to clemastine 8 mg/day, significantly decreased the P100 latency delay of visual evoked potentials (VEPs) as a sign of myelin repair. In a bicentric, randomized, double-blind, controlled phase IIb clinical trial with a 2-arm parallel group design in patients with SZ, the study will compare the effects of aerobic exercise training plus clemastine vs. aerobic exercise training plus placebo over a period of 3 months on 1) everyday functioning and 2) working memory as primary outcomes.

开始日期2024-04-01

申办/合作机构

University Hospital of Ludwig-Maximilians-University

100 项与富马酸氯马斯汀相关的临床结果

登录后查看更多信息

100 项与富马酸氯马斯汀相关的转化医学

登录后查看更多信息

100 项与富马酸氯马斯汀相关的专利（医药）

登录后查看更多信息

1,113

项与富马酸氯马斯汀相关的文献（医药）

2025-06-01·NEUROCHEMICAL RESEARCH

Clemastine Reduces post-stroke Neurodegeneration by Alleviating Endoplasmic Reticulum stress-mediated Demyelination and Cognitive Impairment Through PERK/ATF4/CHOP Signaling Pathway

Article

作者: Bhattacharya, Pallab ; Bhoga, Dipakkumar ; Ghosh, Bijoyani ; Parmar, Krupanshu ; Datta, Aishika ; Karmarkar, Gautam ; Dhingra, Tannu ; Borah, Anupom ; Barik, Anirban ; Malik, Nikita

The progressive brain damage following ischemic stroke is primarily due to oxidative stress and activation of inflammatory pathways. Post-stroke neurodegeneration can lead to the loss of neurons and glial cells, including oligodendrocytes, contributing to demyelination. Following ischemic stroke, reperfusion results in increased intracellular calcium, generation of free radicals, and inflammation culminating in accumulation of misfolded proteins in the endoplasmic reticulum (ER) lumen augmenting the ER stress. ER stress has been shown to aggravate post-stroke neurodegeneration by triggering neuronal apoptosis and also contributing towards demyelination of neurons. To address the limitations of current stroke therapies, repurposing of drugs as future adjunctive therapy may be promising. Clemastine, an antihistaminic drug, improves post stroke outcome as evident in the present study. Male Sprague Dawley (SD) rats were treated with clemastine following ischemic stroke. Harvested brain tissues were subjected to different biochemical assays, molecular assays, and histopathological analysis. Clemastine was able to reduce infarct size, alleviate oxidative stress, improve neuronal count, and functional outcomes. Clemastine downregulated genes and proteins responsible for ER stress, apoptosis and demyelination as shown by the western blot and qPCR results. Our study suggests that clemastine may alleviate endoplasmic reticulum stress-mediated demyelination by modulating PERK/ATF4/CHOP axis, and may be used as one of the adjunctive therapies for stroke in future.

2025-05-01·VETERINARY ANAESTHESIA AND ANALGESIA

Unexpected upper airway obstruction after ear flushing in two cats

Article

作者: Kutter, Annette P N ; Fischer, Nina ; Golini, Lorenzo ; Dennler, Matthias ; Meira, Carolina

This case report outlines complications associated with ear flush procedures in two cats. The first case, a female Domestic Short Hair cat, aged 8 years and weighing 3.9 kg, presented with signs of Horner's syndrome and right-sided facial paralysis. Magnetic resonance imaging revealed bilateral otitis media and right-sided bulla osteolysis. Under general anaesthesia with sevoflurane, a bilateral myringotomy and ear flush was performed. After flushing of the right ear, there was significant swelling on the right side of the head, extending to the left side and with oropharyngeal oedema, which made visualization of the trachea impossible. It was decided not to attempt tracheal extubation. Intravenous (IV) clemastine and topical mannitol were administered to treat a possible drug reaction and decrease oedema, respectively. The cat was transferred to intensive care unit and maintained under general anaesthesia. The lungs were mechanically ventilated, and antimicrobials and steroids were administered IV. The subsequent day, as the swelling and oedema had resolved, successful extubation was performed, and the patient was discharged from the clinic. The second case was a spayed female Domestic Short Hair cat, aged 9 years, weighing 2.4 kg and with a history of ear disease. It had recently developed symptoms of right-sided peripheral vestibular syndrome. Under anaesthesia with sevoflurane, magnetic resonance imaging revealed bilateral otitis media with bulla osteitis. The cat's trachea was extubated after ear flush and myringotomy, followed shortly after by emergency orotracheal reintubation owing to oropharyngeal soft tissue swelling causing upper airway obstruction. The cat was administered glucose and phenylephrine topically and dexamethasone IV. The airway was nebulized with diluted epinephrine. Anaesthesia recovery and extubation were possible a few hours later. The cat recovered in an oxygen cage in the intensive care unit and was administered antimicrobials, maropitant and butorphanol IV and closely monitored overnight. The cat was discharged from the clinic the next day.

2025-04-02·JOURNAL OF NEUROSCIENCE

Long-Term Excessive Alcohol Consumption Enhances Myelination in the Mouse Nucleus Accumbens

Article

作者: Fischer, Inbar ; Gordon, Tamar ; Rahamim, Nofar ; Assaf, Yaniv ; Liran, Mirit ; Barak, Boaz ; Urshansky, Nataly ; Barak, Segev ; Elboim, May

Chronic excessive alcohol (ethanol) consumption induces neuroadaptations in the brain's reward system, including biochemical and structural abnormalities in white matter that are implicated in addiction phenotypes. Here, we demonstrate that long-term (12 week) voluntary ethanol consumption enhances myelination in the nucleus accumbens (NAc) of female and male adult mice, as evidenced by molecular, ultrastructural, and cellular alterations. Specifically, transmission electron microscopy analysis showed increased myelin thickness in the NAc following long-term ethanol consumption, while axon diameter remained unaffected. These changes were paralleled by increased mRNA transcript levels of key transcription factors essential for oligodendrocyte (OL) differentiation, along with elevated expression of critical myelination-related genes. In addition, diffusion tensor imaging revealed increased connectivity between the NAc and the prefrontal cortex, reflected by a higher number of tracts connecting these regions. We also observed ethanol-induced effects on OL lineage cells, with a reduction in the number of mature OLs after 3 weeks of ethanol consumption, followed by an increase after 6 weeks. These findings suggest that ethanol alters OL development prior to increasing myelination in the NAc. Finally, chronic administration of the promyelination drug clemastine to mice with a history of heavy ethanol consumption further elevated ethanol intake and preference, suggesting that increased myelination may contribute to escalated drinking behavior. Together, these findings suggest that heavy ethanol consumption disrupts OL development, induces enhanced myelination in the NAc, and may drive further ethanol intake, reinforcing addictive behaviors.

项与富马酸氯马斯汀相关的新闻（医药）

2025-05-05

·信狐药迅

百济神州BCL-2抑制剂索托克拉提交上市申请|新受理（4.27-5.5）

本周药品注册受理数据，分门别类呈现，一目了然。(4.27-5.5）新药上市申请药品名称企业注册分类受理号索托克拉片百济神州(苏州)生物科技有限公司1CXHS2500043索托克拉片百济神州(苏州)生物科技有限公司1CXHS2500042索托克拉片百济神州(苏州)生物科技有限公司1CXHS2500041索托克拉片百济神州(苏州)生物科技有限公司1CXHS2500040左氨氯地平比索洛尔片(Ⅱ)施慧达药业集团(吉林)有限公司2.3CXHS2500039左氨氯地平比索洛尔片(Ⅰ)施慧达药业集团(吉林)有限公司2.3CXHS2500038新药临床申请药品名称企业注册分类受理号注射用HRS8179北京盛迪医药有限公司1CXHL2500436HRS-1893片山东盛迪医药有限公司1CXHL2500431MDI-1228_mesylate凝胶迈英诺医药科技(珠海)有限公司1CXHL2500435MDI-1228_mesylate凝胶迈英诺医药科技(珠海)有限公司1CXHL2500434MDI-1228_mesylate凝胶迈英诺医药科技(珠海)有限公司1CXHL2500433MDI-1228_mesylate凝胶迈英诺医药科技(珠海)有限公司1CXHL2500432SYN608片杭州圣域生物医药科技有限公司1CXHL2500430SYN608片杭州圣域生物医药科技有限公司1CXHL2500429DF-003胶囊上海药苑生物科技有限公司1CXHL2500428DF-003胶囊上海药苑生物科技有限公司1CXHL2500427DF-003胶囊上海药苑生物科技有限公司1CXHL2500426G201-Na胶囊石家庄以岭药业股份有限公司1CXHL2500425G201-Na胶囊石家庄以岭药业股份有限公司1CXHL2500424ABP-745片杭州新元素药业有限公司1CXHL2500418ABP-745片杭州新元素药业有限公司1CXHL2500417ABP-745片杭州新元素药业有限公司1CXHL2500416177Lu-HX02注射液核欣(苏州)医药科技有限公司1CXHL2500413WS-019湖北午时药业股份有限公司2.2CXHL2500415雷美替胺双释片南京三迭纪医药科技有限公司2.2CXHL2500420OLP-210片深圳奥礼生物科技有限公司2.2CXHL2500423OLP-210片深圳奥礼生物科技有限公司2.2CXHL2500422OLP-210片深圳奥礼生物科技有限公司2.2CXHL2500421GBI268注射液苏州智耀生物科技有限公司2.2CXHL2500414甲磺酸阿帕替尼片江苏恒瑞医药股份有限公司2.4CXHL2500419FL115注射液苏州复融生物技术有限公司1CXSL2500350BAT4406F注射液百奥泰生物制药股份有限公司1CXSL2500349人脐带间充质干细胞注射液深圳市北科生物科技有限公司1CXSL2500348注射用BGB-B3227广州百济神州生物制药有限公司1CXSL2500347注射用重组病毒巨噬细胞炎性蛋白广州弘润生物科技有限公司1CXSL2500346靶向CD19和CD22 的嵌合抗原受体自体T细胞注射液上海医药集团生物治疗技术有限公司1CXSL2500344注射用YL242苏州宜联生物医药有限公司1CXSL2500343IMD101 注射液上海英脉德医疗科技有限公司1CXSL2500339BBT001注射液杉竹曜(北京)生物医药科技有限公司1CXSL2500342NouvNeu004睿健毅联医药科技(成都)有限公司1CXSL2500341注射用SKB518四川科伦博泰生物医药股份有限公司1CXSL2500334PM8002注射液普米斯生物技术(珠海)有限公司1CXSL2500333注射用DB-1311映恩生物制药(苏州)有限公司1CXSL2500337注射用BL-B01D1成都百利多特生物药业有限责任公司1CXSL2500332依沃西单抗注射液康方赛诺医药有限公司2.2CXSL2500345SHR-8068注射液苏州盛迪亚生物医药有限公司2.2CXSL2500340SHR-8068注射液苏州盛迪亚生物医药有限公司2.2CXSL2500338贝伐珠单抗注射液苏州盛迪亚生物医药有限公司2.2CXSL2500336阿得贝利单抗注射液上海盛迪医药有限公司2.2CXSL2500335仿制药申请药品名称企业注册分类受理号碳酸司维拉姆干混悬剂金陵药业股份有限公司南京金陵制药厂3CYHS2501638美洛昔康注射液浙江圣兆药物科技股份有限公司3CYHS2501635硫代硫酸钠注射液海南卓科制药有限公司3CYHS2501634复方电解质醋酸钠注射液浙江赛默制药有限公司3CYHS2501623法莫替丁注射液山东新华制药股份有限公司3CYHS2501619坎地氢噻片桂林华信制药有限公司3CYHS2501617重酒石酸间羟胺注射液上海现代哈森(商丘)药业有限公司3CYHS2501612复合磷酸氢钾注射液河北天成药业股份有限公司3CYHS2501611布美他尼注射液国药集团容生制药有限公司3CYHS2501608盐酸利多卡因凝胶舒美奇成都生物科技有限公司3CYHS2501605盐酸倍他司汀片锦州九泰药业有限责任公司3CYHS2501601小儿多种维生素注射液(13)合肥市未来药物开发有限公司3CYHS2501600螺内酯口服混悬液成都倍特得诺药业有限公司3CYHS2501599复方聚乙二醇(3350)电解质口服溶液澳诺(中国)制药有限公司3CYHS2501587富马酸氯马斯汀口服溶液广东华南药业集团有限公司3CYHS2501592苯溴马隆片浙江江北药业有限公司3CYHS2501591琥珀酸亚铁片陕西巨成生物医药生产力促进中心有限公司3CYHS2501589磷酸奥司他韦颗粒重庆万霖生物医药科技有限公司3CYHS2501595沙库巴曲缬沙坦钠片山东新华制药股份有限公司4CYHS2501636布瑞哌唑片北京仁众药业有限公司4CYHS2501628盐酸奥洛他定滴眼液广州维奥康药业科技有限公司4CYHS2501637盐酸特比萘芬喷雾剂四川美大康华康药业有限公司4CYHS2501633硫酸特布他林雾化吸入用溶液云南龙海天然植物药业有限公司4CYHS2501632注射用阿立哌唑丽珠集团丽珠制药厂4CYHS2501631骨化三醇软胶囊浙江华润三九众益制药有限公司4CYHS2501630二甲双胍恩格列净片(I)北京康立生医药技术开发有限公司4CYHS2501629厄贝沙坦氢氯噻嗪片广州白云山天心制药股份有限公司4CYHS2501627盐酸贝尼地平片珠海优润医药科技有限公司4CYHS2501626钆塞酸二钠注射液广州康臣药业有限公司4CYHS2501625米库氯铵注射液浙江恒研医药科技有限公司4CYHS2501624左氧氟沙星片常州兰陵制药有限公司4CYHS2501622利丙双卡因乳膏广东泰恩康制药厂有限公司4CYHS2501621玻璃酸钠滴眼液北京仁众药业有限公司4CYHS2501620艾拉莫德片江苏悦兴药业有限公司4CYHS2501616氧(液态)四川盈德万华气体有限公司4CYHS2501615阿达帕林凝胶浙江寰领医药科技有限公司4CYHS2501614孟鲁司特钠片重庆药友制药有限责任公司4CYHS2501613二甲双胍恩格列净片(I)涿州东乐制药有限公司4CYHS2501618佩玛贝特片湖南科伦制药有限公司4CYHS2501610二十碳五烯酸乙酯软胶囊博瑞制药(苏州)有限公司4CYHS2501609盐酸乙哌立松片湖南九典制药股份有限公司4CYHS2501607甲磺酸溴隐亭片广州大光制药有限公司4CYHS2501606达格列净二甲双胍缓释片(III)北京四环科宝制药股份有限公司4CYHS2501603达格列净二甲双胍缓释片(I)北京四环科宝制药股份有限公司4CYHS2501602双氯芬酸二乙胺乳胶剂杭州朱养心药业有限公司4CYHS2501598阿达帕林凝胶唐山红星药业有限责任公司4CYHS2501604乳酸钠林格注射液湖南先施制药有限公司4CYHS2501588艾曲泊帕乙醇胺片鲁南贝特制药有限公司4CYHS2501586匹维溴铵片浙江恒研医药科技有限公司4CYHS2501593恩格列净片东北制药集团沈阳第一制药有限公司4CYHS2501590富马酸伏诺拉生片山东普瑞曼药业有限公司4CYHS2501584注射用头孢唑肟钠浙江恒研医药科技有限公司4CYHS2501597注射用头孢唑肟钠浙江恒研医药科技有限公司4CYHS2501596阿哌沙班片广东彼迪药业有限公司4CYHS2501594注射用吗替麦考酚酯四川科瑞德制药股份有限公司4CYHS2501585盐酸米诺环素泡沫剂上海则正医药科技股份有限公司4CYHL2500089倍氯米松福莫特罗吸入气雾剂合肥力成药业有限公司4CYHL2500088盐酸米诺环素泡沫剂深圳珐玛易药品科技有限公司4CYHL2500087进口申请药品名称企业注册分类受理号司替戊醇胶囊Biocodex5.1JXHS2500056司替戊醇胶囊Biocodex5.1JXHS2500055镥[177Lu] 特昔维匹肽注射液Novartis Pharma Schweiz AG5.1JXHS2500054帕博利珠单抗注射液Merck Sharp & Dohme LLC3.1JXSS2500051TQJ230注射液Novartis Pharma AG1JXHL2500103177Lu-HuJ591单抗注射液Telix Pharmaceuticals (Innovations) Pty Ltd1JXSL2500069Mezagitamab注射剂Takeda Development Center Americas, Inc.1JXSL2500067Mezagitamab注射剂Takeda Development Center Americas, Inc.1JXSL2500066VHB937注射用浓溶液Novartis Pharma AG1JXSL2500065中药相关申请药品名称企业注册分类受理号TFA003片杭州康恩贝制药有限公司2.1CXZL2500028百令胶囊杭州中美华东制药有限公司2.3CXZL2500027百令胶囊杭州中美华东制药有限公司2.3CXZL2500026注：绿色字体部分为潜在首仿品种；不包含原料药、医用氧、注射用水、氯化钠或葡萄糖注射液等申请，不包含再注册、一次性进口、技术转移、复审申请。

申请上市临床申请

2024-04-03

·生物制药小编

什么Biotech让强生和百济二股东看好？

昨日（4月1日），随着Contineum Therapeutics的FORM S-1文件更新披露，已经可以看到这家Biotech IPO过程的具体细节。此次IPO预计将会以16-18美元/每股发放880万股，最终募股规模有可能超过此前预计的1.5亿美元。股东方面，之前就是Contineum Therapeutics投资人的强生附属基金JJDC，知名资本Sectoral Asset Management，还吸引来了曾经的Seagen大股东和现在百济二股东Baker Brother。Contineum Therapeutics将是今年第八家申请上市的Biotech企业，但是与之前几家IPO的比如说：Alto Neuroscience、ArriVent Biopharma、CG Oncology、Kyverna Therapeutics和Metagenom较为不同的是，这家小分子药物公司的IPO募股金额相对较高，适应症上主要开发多发性硬化症（MS）这一红海市场，目前管线还都处于临床早期。按理来说，多发性硬化症是罕见病中竞争较为激烈的红海市场，从市场角度来看，曾经的霸主Biogen（渤健）这几年都因为仿制药和竞争对手罗氏的深度参与，销量大幅下滑了。竞争激烈程度可见一斑。而在这种情况下，这家公司能得到强生看重，肯定有其特殊的地方。管线概览虽然同样是MS，但是Contineum的管线机制与许多企业大相径庭。现有的MS治疗手段如富马酸二甲酯，Ocrelizumab等治疗手段都是通过抑制炎症的途径来进行治疗的。而Contineum Therapeutics已经明确适应症的管线采用的是两种与现有治疗药物机制完全不同的路线：一种是溶血磷脂酸1受体（LPA1R）抑制剂PIPE-791，另外一种是毒蕈碱1型M1受体（M1R）抑制剂PIPE-307。此外，这家公司还有一款不明适应症的管线：LPA1R抑制剂CTX-343。虽然这两款药物都有两种不同细分的MS适应症，但这家企业也没死磕MS，PIPE-791还能用于开发特发性肺纤维化（IPF），PIPE-307则被额外开发用于抑郁症。强生似乎很看重PIPE-307，Contineum Therapeutics（当时还叫Pipeline Therapeutics）在去年4月与强生授权交易中，不仅获得了5000万美元的预付款，有望获得10亿美元里程碑付款，还获得了2500万美元的股权投资和2500万美元的现有投资人投资。LPA1R抑制剂的开发溶血磷脂酸（LPA）是一种通过特异性G蛋白偶联受体（LPAR）发挥作用的生物活性介质，目前对其在纤维化病因中的作用有所了解。在许多器官中，纤维化与LPA产生增加以及某些LPAR亚型（主要是LPA1R）表达增加有关。所以PIPE-791的适应症是IPF似乎不难理解，而在MS中的应用主要起始于近几年Contineum Therapeutics的开发。MS是一种炎症性脱髓鞘疾病，导致神经元传递中断，最终导致神经变性。目前的治疗重点是抑制免疫系统，以限制炎症和髓鞘的进一步丧失。先前的几篇文献发现，在MS中，炎性脂质、溶血磷脂酸(LPA)水平升高，这种炎症脂质的升高对于MS病情进展是不利的。除了神经炎症，LPA还会抑制少突胶质前体细胞(OPC)分化。而少突胶质前体细胞是产生髓鞘化细胞的细胞，而MS常常伴随着慢性脱髓鞘，抑制LPA可能有助于MS中髓鞘化细胞的再生。而PIPE-791就是这一成果转化的产物。PIPE-791是首个口服生物可利用的脑渗透LPA1拮抗剂。毒蕈碱1型m1受体抑制剂大部分对毒蕈碱1型m1受体抑制剂的开发都集中在阿尔兹海默症和精神疾病如精神分裂症，但是Contineum Therapeutics竟然将其用于了MS上。机理机制和上述LPA用于MS的类似。以前MS的治疗药物主要通过抑制炎症途径来减少进展，而Contineum的注意力集中在调节髓鞘再生的分子上。MI毒蕈碱乙酰胆碱受体(MIR)已被证明是少突胶质前细胞(OPCs)成熟为少突胶质细胞(OLs)的关键调节剂，少突胶质细胞是制造髓磷脂的细胞。这一发现是基于非选择性抗毒蕈碱化合物，如Clemastine和Benzetropine，并随后通过细胞类型特异性MIR敲除研究验证。基于这一初步发现，Contineum就开始了一项药物化学研究，以发现一种新的MIR选择性拮抗剂。最初产生的拮抗剂是是PIPE-359，后续跟进迭代产生了PIPE-307。临床前研究表明，PIPE307可诱导功能性髓鞘再生。点评总的来看，PIPE307和PIPE-791在机制上其实和现有MS并不冲突，甚至能够互补，现有治疗手段大多着重于抑制炎症途径，而抑制炎症途径只能起到延缓作用，联合使用这两款药物可能改变现有MS的格局。这可能是强生对这家企业另眼先看的原因。不过也值得注意的是，虽然PPT讲得好是一回事，但是实际患者再生的有效性是另外一回事。PIPE307和PIPE-791是否能在疗效上展现出具有统计学意义上的临床改善或许才是关键。参考来源：Rancoule C, Pradère JP, Gonzalez J, Klein J, Valet P, Bascands JL, Schanstra JP, Saulnier-Blache JS. Lysophosphatidic acid-1-receptor targeting agents for fibrosis. Expert Opin Investig Drugs. 2011 May;20(5):657-67. doi: 10.1517/13543784.2011.566864. Epub 2011 Mar 24.https://www.contineum-tx.com/wp-content/uploads/2023/04/GRC-Glial-biology-conference-030123.pdf

IPO引进/卖出临床1期

2023-09-13

·米内网

【获批】重磅罕见病药首仿，远大医药拿下

精彩内容9月12日，远大医药公告称，公司以仿制3类报产的卡谷氨酸分散片获批上市，为国内首仿+首家过评。该产品用于治疗高氨血症，是公司在心脑血管急救领域罕见病方向的重大研发进展。卡谷氨酸分散片有效成分卡谷氨酸是N-乙酰谷氨酸(NAG)结构类似物，用于治疗成人或儿童由N-乙酰谷氨酸合成酶(NAGS)缺乏症、异戊酸血症(IVA)、甲基丙二酸血症(MMA)或丙酸血症(PA)所引起的高氨血症。目前，卡谷氨酸分散片已经在欧美等多个国家和地区上市，并被纳入FDA的孤儿药品目录，是FDA批准的第一种也是唯一一种用于治疗由MMA和PA引发的高氨血症的药物。远大医药卡谷氨酸分散片卡谷氨酸分散片原研厂家为Recordati，于2023年6月27日在国内获批上市，已通过2023国谈药品初审。远大医药的卡谷氨酸分散片以仿制3类批产并视同过评，为国内首仿+首家过评。心脑血管急救板块是远大医药重点布局领域，公司已有近30个品种获批上市，在研产品超过20款，涉及多款罕见病药物，用于治疗韦斯特综合征的氨己烯酸口服溶液用散上市申请在审中。米内网数据显示，远大医药已有13个品种通过或视同通过一致性评价，5个品种重酒石酸去甲肾上腺素注射液、碳酸氢钠片、格列吡嗪片、富马酸氯马斯汀注射液、卡谷氨酸分散片为国内首家过评。资料来源：米内网数据库、公司公告本文为原创稿件，转载请注明来源和作者，否则将追究侵权责任。投稿及报料请发邮件到872470254@qq.com稿件要求详询米内微信首页菜单栏商务及内容合作可联系QQ：412539092【分享、点赞、在看】点一点不失联哦

上市批准一致性评价孤儿药

100 项与富马酸氯马斯汀相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
D00666	富马酸氯马斯汀	R06AA04 D04AA14	DB00283

研发状态

批准上市

10 条最早获批的记录,

后查看更多信息

适应症	国家/地区	公司	日期
变应性结膜炎	美国	Novartis Pharmaceuticals Corp.	1977-02-25
普通感冒	日本	NISSIN Pharmaceutical Co., Ltd.	1970-01-17
皮炎	日本	NISSIN Pharmaceutical Co., Ltd.	1970-01-17
湿疹	日本	NISSIN Pharmaceutical Co., Ltd.	1970-01-17
瘙痒	日本	NISSIN Pharmaceutical Co., Ltd.	1970-01-17
过敏性鼻炎	日本	NISSIN Pharmaceutical Co., Ltd.	1970-01-17
荨麻疹	日本	NISSIN Pharmaceutical Co., Ltd.	1970-01-17

未上市

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
季节性过敏性鼻炎	临床2期	美国	NovaDel Pharma, Inc.	-

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT06039137 (H1-Switch Study, Pubmed \| JCO Oncol Pract)	N/A	-	-	Intravenous Clemastine	廠鹽網鬱願製窪艱膚齋(獵製齋範壓蓋製齋憲糧) = 齋顧淵鹹選醖壓簾壓顧艱顧醖遞齋顧觸襯蓋觸 (齋窪願餘糧醖窪製蓋鏇, -3.4 ~ 1.1)	积极	2024-06-07
				Oral Cetirizine	廠鹽網鬱願製窪艱膚齋(獵製齋範壓蓋製齋憲糧) = 鏇壓鹹鏇襯醖獵簾廠範艱顧醖遞齋顧觸襯蓋觸 (齋窪願餘糧醖窪製蓋鏇, -3.4 ~ 1.1)
TRAP-MS (ACTRIMS2024)	N/A	慢性进行性多发性硬化	9	Clemastine Fumarate	製顧遞壓願願衊衊範製(選觸築醖艱膚鹽襯鹽糧) = 廠淵憲齋齋艱製鹹壓齋選鏇鏇築範觸製顧夢範 (選憲選鬱網繭願艱廠構 )	不佳	2024-02-29
NCT02040298 (ReBUILD, CTgov)	临床2期	复发-缓解型多发性硬化	50	Clemastine (Clemastine)	繭積糧壓網願觸淵夢鑰(遞醖選窪積壓鑰願糧鬱) = 觸築簾蓋網壓憲膚鏇鑰顧衊憲選廠選積醖淵簾 (醖繭衊糧積蓋選繭積顧, 11.5) 更多	-	2021-07-15
				Placebo+clemastine (Placebo)	繭積糧壓網願觸淵夢鑰(遞醖選窪積壓鑰願糧鬱) = 繭顧糧糧淵襯範夢襯艱顧衊憲選廠選積醖淵簾 (醖繭衊糧積蓋選繭積顧, 10.9) 更多