A randomized double blind placebo controlled multicenterstudy to assess the efficacy and tolerability of tolperisone as add ontreatment with standardized NSAID of acute non specific low back pain.

开始日期2022-03-28

申办/合作机构-

NCT04671082

/ Completed临床3期

A Phase 3, 14-Day, Double-blind, Randomized, Placebo-Controlled, Multicenter Study of the Efficacy and Safety of Tolperisone in Subjects With Pain Due to Acute Back Muscle Spasm

This is a double-blind, randomized, placebo-controlled, multicenter study of the efficacy and safety of tolperisone (a non-opioid) or placebo administered in subjects with pain due to acute back muscle spasm.

开始日期2020-12-15

申办/合作机构

Neurana Pharmaceuticals, Inc.

NCT04465266

/ Completed临床1期

A Phase 1 Crossover Study of Single and Multiple Dose Pharmacokinetics, and Dose Linearity, of Tolperisone in Healthy Subjects

This is a randomized, single-blind, single and multiple dose crossover subjects in healthy adult subjects

开始日期2020-07-28

申办/合作机构

Neurana Pharmaceuticals, Inc.

100 项与盐酸托哌酮相关的临床结果

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100 项与盐酸托哌酮相关的转化医学

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100 项与盐酸托哌酮相关的专利（医药）

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192

项与盐酸托哌酮相关的文献（医药）

2025-01-01·Journal of Pharmaceutical and Biomedical Analysis

Separation of tolperisone and its degradation products by a dual cyclodextrin capillary electrophoresis system to study their potential role in allergic events

Article

作者: Tábi, Tamás ; Lakatos, Péter P. ; Szökő, Éva ; Lakatos, Péter P ; Boldizsár, Imre ; Csernák, Orsolya ; Ignáth, Zsuzsanna

Tolperisone is a centrally acting muscle relaxant that has been used for the treatment of post-stroke spasticity and low back pain. Recently, the safety of tolperisone pharmaceutical products has been reassessed due to growing concerns over allergic adverse events. Reactive degradants of tolperisone may be responsible for these hypersensitivity reactions. By forming adducts with proteins, they may act as haptens that could evoke allergic reactions. The objective of this study was to examine the presence of these degradants in tolperisone pharmaceutical products and to assess their reactivity to elucidate their possible role in the pro-allergic effect of tolperisone. For this purpose, capillary electrophoresis UV detection (CE-UV) method was developed and validated for the quantification of degradants. A dual cyclodextrin system was applied to achieve the appropriate migration order enabling the analysis of 2-methyl-1-(4-methylphenyl)prop-2-en-1-one (MMP) and 1-(4-methylphenyl)propan-1-one (MMPO) in the presence of high concentrations of tolperisone. MMP was identified as the main degradant in forced degradation tests of the active pharmaceutical ingredient. Differences in MMP content of tolperisone products by different manufacturers have also been found, highlighting the role of formulation in their stability. High reactivity of MMP was demonstrated as rapid and almost complete adduct formation with cysteine was found. This degradant thus might be responsible for the allergic adverse effects of tolperisone even when it is present in trace amounts in tablets by readily reacting with proteins in vivo.

2024-10-01·Science of The Total Environment

Metabolomic study on ostracods exposed to environmentally relevant concentrations of five pharmaceuticals selected via a novel approach

Article

作者: Chojnacka, Justyna ; Giebułtowicz, Joanna ; Michorowska, Sylwia ; Marek, Dominik ; Kucharski, Dawid ; Nałęcz-Jawecki, Grzegorz

Pharmaceuticals (PhACs) are increasingly detected in aquatic ecosystems, yet their effects on biota remain largely unknown. The environmentally relevant concentrations of many PhACs may not result in individual-level responses, like mortality or growth inhibition, traditional toxicity endpoints. However, this doesn't imply the absence of negative effects on biota. Metabolomics offers a more sensitive approach, detecting responses at molecular and cellular levels and providing mechanistic understanding of adverse effects. We evaluated bioaccumulation and metabolic alterations in a benthic ostracod, Heterocypris incongruens, exposed to a mixture of five PhACs (carbamazepine, tiapride, tolperisone, propranolol and amlodipine) at environmentally relevant concentrations for 7 days using liquid chromatography coupled with mass spectrometry. The selection of PhACs was based, among other factors, on risk quotient values determined using toxicological data available in the literature and concentrations of PhACs quantified in our previous research in the sediments of the Odra River estuary. This represents a novel approach to PhACs selection for metabolomic studies that considers strictly quantitative data. Amlodipine and tolperisone exhibited the highest bioaccumulation. Significant impacts were observed in Alanine, aspartate and glutamate metabolism, Starch and sucrose metabolism, Arginine biosynthesis, Histidine metabolism, Tryptophan metabolism, Glycerophospholipid metabolism, and Glutathione metabolism pathways. Most of the below-individual-level responses were likely nonspecific and related to dysregulation in energy metabolism and oxidative stress response. Additionally, some pharmaceutical-specific responses were also observed. Therefore, untargeted metabolomics can be used to detect metabolic changes resulting from environmentally relevant concentrations of PhACs in aquatic ecosystems and to understand their underlying mechanism.

2024-05-01·Biomedicine & Pharmacotherapy

Tolperisone hydrochloride improves motor functions in Parkinson’s disease via MMP-9 inhibition and by downregulating p38 MAPK and ERK1/2 signaling cascade

Article

作者: Hassan, Tazree ; Chowdhury, Fowzia Afsana ; Uddin, Kabir M ; Hossain, Md Mainul ; Mallick, Anup ; Mostafa, Irona ; Rahman, Mahbubur ; Sharmin, Ayesha ; Zaman, Bushra ; Bosu, Tory ; Chowdhury, Humayra Noor ; Islam, Mm Shanjid ; Esha, Nusrat Jahan Ikbal ; Ahmed, Shamim

The mitogen-activated protein kinase (MAPK) signaling pathway, particularly the p38 MAPK and ERK1/2, has been implicated in the pathogenesis of Parkinson's disease (PD). Recent studies have shown that MAPK signaling pathway can influence the expression of matrix metalloproteinase 9 (MMP-9), known for its involvement in various physiological and pathological processes, including neurodegenerative diseases. This study explores the modulation of MMP-9 expression via the MAPK/ERK signaling cascade and its potential therapeutic implications in the context of PD-associated motor dysfunction. Here, tolperisone hydrochloride (TL), a muscle relaxant that blocks voltage-gated sodium and calcium channels, was used as a treatment to observe its effect on MAPK signaling and MMP-9 expression. Rotenone (RT) exposure in mice resulted in a significant reduction in substantia nigra and primary motor cortex neurons, which were further evidenced by impairments in motor function. When TL was administered, neuron count was restored (89.0 ± 4.78 vs 117.0 ± 4.46/mm²), and most of the motor dysfunction was alleviated. Mechanistically, TL reduced the protein expression of phospho-p38MAPK (1.06 fold vs 1.00 fold) and phospho-ERK1/2 (1.16 fold vs 1.02 fold), leading to the inhibition of MAPK signaling, as well as reduced MMP-9 concentrations (2.76 ± 0.10 vs 1.94 ± 0.10 ng/mL) in the process of rescuing RT-induced neuronal cell death and motor dysfunction. Computational analysis further revealed TL's potential inhibitory properties against MMP-9 along with N and L-type calcium channels. These findings shed light on TL's neuroprotective effects via MMP-9 inhibition and MAPK signaling downregulation, offering potential therapeutic avenues for PD-associated motor dysfunction.

项与盐酸托哌酮相关的新闻（医药）

2023-09-27

·蒲公英Ouryao

中西复方制剂、变更API供应商该怎办？

作者 | 疯子的邂逅来源 | 蒲公英ouryao问:中药品种，原料中包含化学成分、在变更原料药供应商时怎么办？近日，有蒲友反馈，公司有一个中药品种为脑络通胶囊，制剂所用原料为单身细粉（中药提取物）、盐酸托哌酮（API）、甲基橙皮苷（API）、维生素B6（API），现在计划变更盐酸托哌酮（API）、甲基橙皮苷（API）供应商，关于此项变更是属于中等变更、还是微小变更，企业内部意见不一致，出现争峙，主要争议点如下：1、质量管理部：属于中等变更，理由如下：按照《已上市化学药品药学变更研究技术指导原则》（试行）第六项：变更制剂所用的原料药供应商，变更后的原料药为已获批准的原料药按照中等变更管理；《已上市中药药学变更研究技术指导原则》（试行）中有提到，中西复方制剂及中药注射剂的变更研究应充分考虑药品特点、制剂要求，全面关注变更对药品安全性、有效行和质量可控性的影响，并参照相关技术指导原则、技术要求开展相关研究工作，这里边推到的相关技术指导原则就是《已上市化学药品药学变更研究技术指导原则》（试行）。2、研发部：属于中等变更，理由如下：按照变更就高不就低的原则，指导原则尚没有明确说明的情况下应该参照更高的管理制度执行。3、技术部：属于微小变更，理由如下：《已上市化学药品药学变更研究技术指导原则》（试行）适用范围为化学原料药和化学制剂，脑络通胶囊为中药品种，批准文号为Z大头，不因按照此指导原则开展工作。4、生产部：属于微小变更，理由如下：按照《已上市化学药品药学变更研究技术指导原则》（试行）的要求，变更原料药供应商制剂企业应进行质量对比研究、溶出曲线研究，必要时还需要考虑生物等效性研究等，这对于中药品种来说无法实现，虽然《已上市中药药学变更研究技术指导原则》（试行）中没提及此种变更，但是可以按照变更中药材供应商的制度执行。蒲友点评：1、确实这种变更是一个特例，实际工作中很少遇到，统一质量部门的意见；2、最终评价变更等级的权利不是在质量手里吗，还讨论什么，直接按死；3、折中下，及时按照微小变更去评价，实际做的工作还是应该按照《已上市化学药品药学变更研究技术指导原则》（试行）里边的要求去开展，把能做的都做了，这样即使后期监管部门提出质疑也好补救，要不然就麻烦了；4、直接问药监局不就OK了吗，这么纠结干嘛，制定告诉你就高不就低；5、3楼的意见算是质量妥协的底线了，如果3楼是搞质量的，那你可就危险了啊，常在河边走哪有不湿鞋啊；关于这个话题，你认为应该是什么等级变更，欢迎留言讨论

核酸药物

2023-03-27

·drugs

Comparative Effectiveness of Meds for Acute Low Back Pain Unclear

MONDAY, March 27, 2023 -- For patients with acute low back pain , the comparative effectiveness and safety of analgesic medications is unclear, according to a systematic review and meta-analysis published online March 22 in The BMJ . Michael A. Wewege, from the University of New South Wales in Sydney, and colleagues conducted a systematic review and network meta-analysis to assess the comparative effectiveness and safety of analgesic medicines for acute nonspecific low back pain. Data were reviewed from 98 randomized controlled trials (15,134 participants), which included 69 medicines and combinations. The researchers observed low or very low confidence in evidence for reduced pain intensity after treatment with tolperisone, aceclofenac plus tizanidine, pregabalin (mean differences, −26.1, −26.1, and −24.7, respectively), and 14 other medicines versus placebo. There was low or very low confidence seen for no difference between the effects of several of these medications. There was moderate to very low confidence noted for increased adverse events with tramadol, acetaminophen plus sustained-release tramadol, baclofen, and acetaminophen plus tramadol compared with placebo (risk ratio, 2.6, 2.4, 2.3, and 2.1, respectively). There was moderate-to-low confidence for these medicines increasing the risk for adverse events compared with other medicines. For secondary outcomes and a secondary analysis of medicine classes, moderate-to-low confidence was also noted. "Despite nearly 60 years of research involving more than 15,000 patients, high quality evidence to guide clinical decisions on analgesic medicines for acute nonspecific low back pain remains limited," the authors write. The Sydney Pharmacy School receives funding from GlaxoSmithKline for a postgraduate scholarship supporting a research student supervised by one of the authors. Abstract/Full Text Posted March 2023

临床结果

2022-09-28

·蒲公英Ouryao

药典委：羟苯磺酸钙、盐酸托哌酮等6个标准草案公示

来源：药典委整理：wangxinglai20042022年09月28日，国家药典委发布了6则标准公示通知，涉及品种分别为白蜂蜡、卡维地洛、盐酸艾司洛尔、羟苯磺酸钙、齐墩果酸和盐酸托哌酮，公示期同为1个月。01白蜂蜡我委拟修订白蜂蜡药用辅料标准，为确保标准的科学性、合理性和适用性，现将拟修订的药用辅料标准第二次公示征求社会各界意见（详见附件）。公示期自发布之日起1个月。请认真研核，若有异议，请及时来函提交反馈意见，并附相关说明、实验数据和联系方式。相关单位来函需加盖公章，个人来函需本人签名，同时将电子版发送至指定邮箱。02 卡维地洛我委拟修订卡维地洛国家药品标准，标准编号：《中国药典》2020年版二部。为确保标准的科学性、合理性和适用性，现将拟修订的卡维地洛国家药品标准公示征求社会各界意见（详见附件）。公示期自发布之日起1个月。请认真研核，若有异议，请及时来函提交反馈意见，并附相关说明、实验数据和联系方式。相关单位来函需加盖公章，个人来函需本人签名，同时将电子版发送至指定邮箱。03 盐酸艾司洛尔我委拟修订盐酸艾司洛尔国家药品标准，标准编号：《中国药典》2020年版二部。为确保标准的科学性、合理性和适用性，现将拟修订的盐酸艾司洛尔国家药品标准公示征求社会各界意见（详见附件）。公示期自发布之日起1个月。请认真研核，若有异议，请及时来函提交反馈意见，并附相关说明、实验数据和联系方式。相关单位来函需加盖公章，个人来函需本人签名，同时将电子版发送至指定邮箱。04 羟苯磺酸钙我委拟修订羟苯磺酸钙国家药品标准，标准编号：《中国药典》2020年版二部。为确保标准的科学性、合理性和适用性，现将拟修订的羟苯磺酸钙国家药品标准公示征求社会各界意见（详见附件）。公示期自发布之日起1个月。请认真研核，若有异议，请及时来函提交反馈意见，并附相关说明、实验数据和联系方式。相关单位来函需加盖公章，个人来函需本人签名，同时将电子版发送至指定邮箱。05 齐墩果酸委拟修订齐墩果酸国家药品标准，标准编号：部颁（二部）第三册。为确保标准的科学性、合理性和适用性，现将拟修订的齐墩果酸国家药品标准公示征求社会各界意见（详见附件）。公示期自发布之日起1个月。请认真研核，若有异议，请及时来函提交反馈意见，并附相关说明、实验数据和联系方式。相关单位来函需加盖公章，个人来函需本人签名，同时将电子版发送至指定邮箱。06 盐酸托哌酮我委拟修订盐酸托哌酮国家药品标准，标准编号：WS-10001-(HD-1072)-2002。为确保标准的科学性、合理性和适用性，现将拟修订的盐酸托哌酮国家药品标准公示征求社会各界意见（详见附件）。公示期自发布之日起1个月。请认真研核，若有异议，请及时来函提交反馈意见，并附相关说明、实验数据和联系方式。相关单位来函需加盖公章，个人来函需本人签名，同时将电子版发送至指定邮箱。联系人：周怡、郭伟电话：010-67079556,010-67079558电子邮箱：zhouyi@chp.org.cn通信地址：北京市东城区法华南里11号楼国家药典委员会办公室邮编：100061

100 项与盐酸托哌酮相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D01507	盐酸托哌酮	M02AX06 M03BX04	DB06264

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
肌张力亢进	德国	SANOCHEMIA Pharmazeutika GmbH	2007-10-16
心血管疾病	中国	南京白敬宇制药有限责任公司	1986-01-01
肌肉痉挛	瑞士	Labatec Pharma SA	1966-08-24

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
急性疼痛	临床3期	美国	Neurana Pharmaceuticals, Inc.	2020-12-15
背痛	临床3期	美国	Neurana Pharmaceuticals, Inc.	2020-12-15
脊柱前凸	临床3期	美国	Neurana Pharmaceuticals, Inc.	2020-12-15
痉挛	临床3期	美国	Neurana Pharmaceuticals, Inc.	2020-12-15
多发性硬化症	临床3期	乌克兰	Avigen, Inc.	2007-09-01
多发性硬化症	临床3期	俄罗斯	Avigen, Inc.	2007-09-01
多发性硬化症	临床3期	德国	Avigen, Inc.	2007-09-01
多发性硬化症	临床3期	塞尔维亚	Avigen, Inc.	2007-09-01
多发性硬化症	临床3期	捷克	Avigen, Inc.	2007-09-01
肌肉痉挛	临床3期	捷克	SANOCHEMIA Pharmazeutika GmbH	-

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临床结果

适应症

分期

评价

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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


NCT04671082 (RESUME-1, Biospace) 人工标引	临床3期	肌肉痉挛	1,004	Tolperisone Hydrochloride	(鬱淵鹽壓淵餘憲顧積窪) = failed to meet its primary endpoints 窪鹽艱鹽選膚壓觸獵醖 (觸糧簾艱艱網遞憲築壓 )	积极	2022-03-22
NCT03802565 (STAR, CTgov)	临床2期	腰痛 \| 痉挛 \| 急性疼痛 \| 肌痛性痉挛 \| 脊柱前凸	415	Tolperisone (Tolperisone 50 mg)	觸構艱廠選鬱構網網鏇(窪鹽壓蓋鏇蓋鹹構糧鏇) = 齋襯簾顧遞廠鑰鑰遞餘膚醖憲鑰製獵醖衊鏇範 (鹹選鹽遞糧憲範構鏇鹽, 選獵餘構觸襯顧夢獵鹽 ~ 範鹽淵壓範窪選齋觸願) 更多	-	2020-11-10
NCT03802565 (STAR, CTgov)	临床2期	腰痛 \| 痉挛 \| 急性疼痛 \| 肌痛性痉挛 \| 脊柱前凸	415	Tolperisone (Tolperisone 100 mg)	觸構艱廠選鬱構網網鏇(窪鹽壓蓋鏇蓋鹹構糧鏇) = 窪積簾鑰襯蓋築膚鑰網膚醖憲鑰製獵醖衊鏇範 (鹹選鹽遞糧憲範構鏇鹽, 夢鬱窪齋鬱築製齋壓築 ~ 簾構鑰鹹構襯範鹹鬱蓋) 更多	-	2020-11-10