更新于：2024-11-04

Nitrazepam

硝西泮

更新于：2024-11-04

概要

概要

基本信息

药物类型

小分子化药

别名

1,3-dihydro-7-nitro-5-phenyl-2H-1,4-benzodiazepin-2-one、2,3-dihydro-7-nitro-5-phenyl-1H-1,4-benzodiazepin-2-one、7-nitro-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one

+ [26]

靶点

GABAA receptor

作用机制

GABAA receptor激动剂(γ-氨基丁酸 A 受体激动剂)

治疗领域

神经系统疾病其他疾病

在研适应症

麻醉强直阵挛性癫痫癫痫+ [1]

非在研适应症-

原研机构-

在研机构

Alfresa Pharma Corp.

华中药业股份有限公司

Kyowa Pharmaceutical Industry Co., Ltd.

非在研机构-

最高研发阶段批准上市

首次获批日期

(1965-01-01),

癫痫入睡和睡眠障碍

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

分子式C15H11N3O3

InChIKeyKJONHKAYOJNZEC-UHFFFAOYSA-N

CAS号146-22-5

关联

项与硝西泮相关的临床试验

NCT02374567 / Terminated临床3期IIT

Pharmacovigilance in Gerontopsychiatric Patients

The purpose of this multicenter-study is to investigate safety of psychopharmacological treatment and rates of adverse drug reactions in gerontopsychiatric inpatients. Elderly people are at higher risk for developing side effects under pharmacological treatment due to an altered metabolic situation, higher comorbidity rates and often polypharmacy. Furthermore gerontopsychiatric patients can often not articulate their symptoms clearly, for example due to pronounced cognitive impairment.
The aim of the study is to gain valid data of possible adverse drug reaction rates, their potential risk factors and outcome, as well as medical prescription practises.
To assess these outcomes an intensive pharmacovigilance-monitoring will be conducted at the five participating study sites.
At Baseline demographic data, previous and present disorders, use of drugs, previous and present medication, quality of life, cognitive function, physical examination results, laboratory results and ECG will be assessed.
Afterwards patients are visited weekly and screened for possible adverse drug reactions. All adverse drug reactions will be coded in the MedDRA-system.
In case of a possible serious adverse drug reaction serum levels of all psychotropic substances applicated will be assessed. Drug combinations will be analysed using an established advanced bioinformatic tool (mediQ). Diagnosis, medication intake and possible adverse drug reactions are documented continually.
2 weeks after discharge from the ward, patients will be contacted by phone to assess catamnestic data.

开始日期2015-01-01

申办/合作机构

Hannover Medical School

IRCT2013092414552N4 / CompletedN/AIIT

Nitrazepam versus Diazepam as intermittent prophylaxis for febrile seizures

开始日期2011-06-05

申办/合作机构

Zanjan University of Medical Sciences

NCT00707915 / Completed临床4期IIT

Effects of Discontinuation of Benzodiazepine-derivative Hypnotics on Cognitive and Motor Functions in Elderly Persons: a Pilot Study

Benzodiazepines (BZDs) have been reported to cause negative impacts on motor as well as cognitive functions, which in turn could result in lethal incidents including falls especially in the elderly. This notwithstanding, few trials have evaluated a feasibility and benefits of discontinuing BZD-derivative hypnotics in a systematic manner in this frail population. In this 8-week open-label study, we examined changes in motor and cognitive functions following the discontinuation of BZD hypnotics in older persons.
OBJECTIVES & HYPOTHESES
Primary Objective The primary objective is to examine the feasibility of discontinuing BZD-derivative hypnotics in older people.
Secondary Objectives
One of the secondary objectives is to examine the magnitude of discontinuing BZD-derivative hypnotics in the stability of body.
Another secondary objective is to examine the magnitude of discontinuing BZD-derivative hypnotics in cognitive function.
Hypotheses
1. More than 80% of the participants will complete and tolerate all the study procedures.
2a. Participants will show an improvement in the stability of body. 2b. Participants will show an improvement in the cognitive function globally as well as specifically in attention.

开始日期2008-01-01

申办/合作机构-

100 项与硝西泮相关的临床结果

登录后查看更多信息

100 项与硝西泮相关的转化医学

登录后查看更多信息

100 项与硝西泮相关的专利（医药）

登录后查看更多信息

1,257

项与硝西泮相关的文献（医药）

2025-01-01·JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS

Repeated lyophilization: A neo-method for urine-based reference materials preparation

Article

作者: Liu, Yu ; Zhi, Yujie ; Zhang, Zhen ; Jin, Wenhui ; Hu, Jing ; Liu, Wei ; Zheng, Qiongying ; Zhang, Wenping ; Lu, Jiayue ; Dou, Quanlu ; Chen, Hang

In urine drug testing, a cut-off value is often imposed to determine whether the sample is negative or positive. A matrix containing a reference substance helps counteract the adverse effects of the urine matrix across different laboratories to improve the consistency of final results. However, as a biological matrix, urine is prone to corruption and other problems that make it difficult to use as a reference sample. In this study, morphine, nitrazepam, lorazepam, buprenorphine, zolpidem, midazolam, diazepam, and clozapine commonly used in clinical practice were selected as target analytes, and the preparation process was further optimized to repeated lyophilization, in order to obtain more effective, stable, and accurate urine matrix reference materials (mRMs). The appropriate urine density (1.010-1.017 kg/m³) for preparing lyophilized samples was investigated through density determination. Conducting repeated lyophilizations resulted in a denser powder with reduced susceptibility to collapse and improved the quality of lyophilized urine samples. Lyophilized urine mRMs could be stored at room temperature for one month or under refrigeration conditions (4 ℃) for six months.

2024-10-28·JOURNAL OF ANALYTICAL TOXICOLOGY

Elucidating the potential role of microorganisms in postmortem biotransformation: a comparison of clonazolam and its metabolite in postmortem and DUID cases

Article

作者: Papsun, Donna M ; Casey, Brittany K ; Mudd, Anna

Abstract:

Clonazolam is a designer triazolobenzodiazepine first synthesized in 1971 and is primarily used for its anxiolytic and sedative effects. It became a drug of misuse in 2012 and is known for its high potency and long duration of effect. Previous studies of nitrobenzodiazepines, such as nitrazepam, clonazepam, and flunitrazepam, as well as their metabolites, have demonstrated that bacterial species native to the gastrointestinal tract and active during postmortem (PM) decomposition are capable of affecting positivity and compound-to-metabolite ratios. Further studies have not been performed with clonazolam; however, it possesses the nitro functional group necessary for this biotransformation. To understand whether clonazolam may be similarly affected, PM cases (n = 288) and driving under the influence of drugs (DUID, n = 54) cases, positive for 8-aminoclonazolam reported by NMS Laboratories from 2020 to 2023, were selected for inclusion in this study. Concentrations of clonazolam and 8-aminoclonazolam were evaluated, and concurrent identification of parent drugs and their metabolites occurred less frequently in PM cases (n = 1, 0.30% of cases) than in DUID cases (n = 21, 38% of cases). The clonazolam concentration in one PM case was 13 ng/mL. In DUID cases, the median clonazolam concentration was 4.0 ng/mL and ranged from 2.0 to 10 ng/mL. 8-Aminoclonazolam had median concentrations of 13 and 19 ng/mL, with ranges 2.0–580 and 2.8–59 ng/mL for PM and DUID cases, respectively. Due to the ever-changing landscape of the designer benzodiazepine market, in vitro studies of PM microbial biotransformation of clonazolam are unavailable. The data reported herein provide valuable information in the absence of such studies and represent an alternative method of investigating this phenomenon as a potential cause of parent nitrobenzodiazepine to metabolite conversion.

2024-09-23·Biomolecules

Enhanced Anticancer Activity of 7MeERT over Ertredin: A Comparative Study on Cancer Cell Proliferation and NDUFA12 Binding.

Article

作者: Atsumi, Sonoko ; Kwon, Ho Jeong ; Park, Se In ; Kawada, Manabu ; Onodera, Takefumi ; Nosaka, Chisato ; Adachi, Hayamitsu ; Shibuya, Masabumi ; Watanabe, Takumi

We have previously identified Ertredin (3-(2-amino-5-bromophenyl) quinoxalin-2(1H)-one) as a compound that suppresses 3D spheroid formation and tumorigenesis in NIH3T3 cells induced by Epidermal Growth Factor Receptor variant III (EGFRvIII) transduction. One of its targets has been shown to be NDUFA12 (NADH Dehydrogenase (Ubiquinone) 1 Alpha Subcomplex Subunit 12), a component protein of oxidative phosphorylation complex I. In this report, we compared the growth inhibitory activity of Ertredin with its methylated analogue 7MeERT (3-(2-amino-5-bromophenyl)-7-methylquinoxalin-2(1H)-one) on human cancer cells. 7MeERT induced the inhibition of the proliferation of various cancer cells similarly to Ertredin and showed higher activity in glioblastoma cells, A431 cells overexpressing EGFR (wild type), and multiple myeloma cells. Molecular docking analysis and a Cellular Thermal Shift Assay (CETSA) suggested that 7MeERT binds to NDUFA12 similarly to Ertredin. The binding of 7MeERT and Ertredin to NDUFA12 in glioblastoma was further supported by the inhibition of the oxygen consumption rate. These results suggest that 7MeERT also binds to NDUFA12, inhibits oxidative phosphorylation, and has a higher anti-cancer cell growth inhibitory activity than Ertredin.

项与硝西泮相关的新闻（医药）

2024-07-23

·Outsourcing Pharma

FDA approves Rusan Pharma’s manufacturing facility in India, paving the way for expanded US presence

This significant milestone, achieved following a comprehensive five-day on-site inspection from April 29 to May 3, 2024, marks a critical step in Rusan Pharma’s expansion into the US API market. Dr Kunal Saxena, managing director of Rusan Pharma, said: “This GMP approval by the US Food and Drug Administration underscores our unwavering commitment to maintaining the highest standards of quality and manufacturing excellence, expanding our global presence and credibility. This achievement instils confidence in our partners and clients, reassuring them of our dedication to excellence in producing high-quality APIs that meet the most stringent global standards.” The Ankleshwar facility’s GMP approval allows Rusan Pharma to significantly enhance its presence in the US market, particularly with its active US Drug Master File (DMF) for specialized APIs such as Eflornithine Hydrochloride Monohydrate and Nalmefene Hydrochloride. Expansion into the US API market The company plans to expand its API portfolio to include Apomorphine, Buprenorphine, Naloxone, Naltrexone, Nalbuphine, Sodium Oxybate, Clonazepam, Diazepam, Nitrazepam, Oxazepam, and Temazepam. Rusan Pharma's strategic focus includes supplying APIs to US-based companies involved in orphan drugs, addiction treatment, and obesity medications. The US FDA approval will bolster Rusan's capabilities, allowing it to broaden its API product portfolio and increase its footprint in the US pharmaceutical sector. The Ankleshwar facility is also GMP approved by other stringent international agencies, including Health Canada, the European Union (EU), and ANVISA (Brazil). Rusan Pharma has implemented 21-CFR-compliant software solutions such as SAP, Laboratory Information Management System (LIMS), document and quality management systems (DMS & QMS), and electronic logbooks to ensure paperless manufacturing. The company faced and overcame significant challenges in transitioning to these systems, including comprehensive staff training and monitoring. googletag.cmd.push(function () { googletag.display('text-ad1'); }); Strategic international certifications Prior to this approval, Rusan Pharma had established a robust presence in key markets such as Australia, Brazil, Canada, the EU, Mexico, New Zealand, and the United Kingdom. The US FDA's endorsement now enables Rusan to market its APIs to US clients with existing marketing authorizations and those developing new formulations. This approval further strengthens global trust and confidence in Rusan’s products and processes. “Our vision is to be a one-stop solution provider in the niche category of addiction treatment and pain management,” added Dr. Saxena. “Integration with API enables us to remain competitive while promoting our finished formulations in the global market. It also enables us to be independent from other companies for the supply of critical APIs for manufacturing various finished formulations, especially for narcotic and psychotropic products. Timely delivery of quality medicine is key to any pharmaceutical business, and a robust supply of API enables us to achieve a rapid time to market with critical products.” New API manufacturing facility in Pithampur The Ankleshwar manufacturing unit plays a strategic role in Rusan’s manufacturing and distribution network, particularly for critical APIs like fentanyl and buprenorphine. The company’s vision is to ensure the competitive and timely delivery of quality medicines in addiction treatment and pain management sectors. In November 2023, Rusan Pharma inaugurated its second API manufacturing facility in Pithampur SEZ, Madhya Pradesh, with an annual production capacity of up to 400 metric tons, significantly higher than the Ankleshwar plant. By mid-2025, the company plans to seek GMP inspection for this new facility by the US FDA and other international inspecting agencies, aiming to further boost its manufacturing capabilities. Rusan Pharma’s continued expansion and adherence to stringent quality standards underscore its commitment to excellence and its strategic vision of becoming a leading global player in the pharmaceutical industry.

上市批准

2024-07-22

·FiercePharma

Rusan Pharma’s API Plant in Ankleshwar Receives (India) USFDA GMP Approval

None Ankleshwar, India – July 22, 2024 – RUSAN PHARMA PRIVATE LIMITED, a pharmaceutical company based in India specializing in the area of addiction treatment and pain management, recently announced that the United States Food and Drug Administration (USFDA) has granted Good Manufacturing Practice (GMP) approval for its Active Pharmaceutical Ingredient (API) facility in Ankleshwar (Gujarat, India). The approval, received on May 29, 2024, followed a comprehensive five-day on-site inspection conducted from April 29 to May 3, 2024. This milestone marks a significant achievement for the company as it paves the way for it to enter the US API market. With an active US Drug Master File (DMF) for niche APIs like Eflornithine Hydrochloride Monohydrate and Nalmefene Hydrochloride, Rusan Pharma plans to expand its portfolio with additional APIs, including Apomorphine, Buprenorphine, Naloxone, Naltrexone, Nalbuphine, Sodium Oxybate, Clonazepam, Diazepam, Nitrazepam, Oxazepam, and Temazepam. Speaking on the achievement, Dr. Kunal Saxena, Managing Director of Rusan Pharma, highlights, "This GMP approval by the USFDA underscores our unwavering commitment to maintaining the highest standards of quality and manufacturing excellence, expanding our global presence and credibility. This achievement instils confidence in our partners and clients, reassuring them of our dedication to excellence in producing high-quality APIs that meet the most stringent global standards.” The USFDA approval of the Ankleshwar facility is a critical development in Rusan Pharma's strategy to become a key player in the global pharmaceutical industry. Currently, the company supplies APIs to various US-based companies focused on orphan drugs, addiction treatment, and obesity medications. The approval will further enhance Rusan's capabilities, expand its API product portfolio, and increase its footprint in the growing US pharmaceutical sector. Following on-site audits, Rusan’s API facility in Ankleshwar is GMP approved by other stringent international agencies such as Health Canada, the European Union (EU), and ANVISA (Brazil). Rusan implemented 21-CFR-compliant software solutions like SAP, Laboratory Information Management System (LIMS), document & quality management systems (DMS & QMS) and electronic logbooks, ensuring a move towards paperless manufacturing. This transition, along with comprehensive staff training and monitoring, posed significant challenges that the company successfully overcame. Before receiving this approval, Rusan Pharma established a robust presence in key markets such as Australia, Brazil, Canada, EU, Mexico, New Zealand, and the United Kingdom. The USFDA's endorsement enables the company to market its APIs to US clients with existing marketing authorizations and those developing new formulations. This approval further bolsters our customers' and regulatory agencies' trust and confidence in us globally. "Our vision is to be a one-stop solution provider in the niche category of addiction treatment and pain management. Integration with API enables us to remain competitive, while promoting our finished formulation in the global market. It also enables us to be independent from other companies for the supply of critical APIs for manufacturing of various finished formulations, especially for narcotic and psychotropic products. Timely delivery of quality medicine is key to any pharmaceutical business. Hence, a robust supply of API enables us to achieve a rapid time to market with critical products" adds Dr Kunal Saxena. Rusan’s Ankleshwar manufacturing unit’s strategic role in its manufacturing and distribution network is underscored by its focus on critical APIs like fentanyl and buprenorphine. The company's vision is to be a comprehensive addiction treatment and pain management provider, ensuring competitive and timely delivery of quality medicines. In November 2023, Rusan Pharma inaugurated its second API manufacturing facility in Pithampur SEZ (Madhya Pradesh, India) with an annual production capacity of upto 400 MT, which is significantly higher than the Ankleshwar plant. By mid-2025, the company plans to seek GMP inspection of this new facility by the USFDA and other international inspecting agencies. This expansion aims to boost Rusan's manufacturing capabilities. About Rusan Pharma Pvt Ltd: Rusan Pharma Pvt Ltd. is an integrated global pharmaceutical company and market leader that specializes in the treatment of Addiction and Pain Management. They offer a complete range of super-specialized products in India and globally. Rusan indigenously develops, manufactures, and markets novel APIs and finished formulations and is one of the few notified companies, which is allowed imports of Narcotic Raw Materials (NRM) such as Thebaine, Oripavine, Codeine and Morphine for the purpose of manufacturing various APIs and finished formulation in India and then re-exporting to global markets. Over the years, Rusan has closely worked with Indian and global institutions such as NACO, UNODC, UNOPS, Global Fund, and Ministries of Health to launch Opioid Substitution Therapy in various emerging markets. Rusan Pharma’s strength lies in innovation of New Drug Delivery Systems (NDDS) such as transdermal patches, implants, depot injections. Rusan was the first company to launch Fentanyl, Buprenorphine and Nicotine Transdermal Patches in India. The company supplies range of products to countries such as India, Canada, Europe, UK, Russia, CIS, South Africa and other South-East Asian countries. Rusan’s API and finished formulation manufacturing facilities hold GMP accreditations such as USFDA, Health Canada, EU, TGA (Australia), SAHPRA (S.Africa), RUSSIA, PIC/S (UKRAINE), ANVISA (Brazil) UAE and many more.

上市批准

2024-05-20

·梅斯医学

被称为「最强安眠药」的氯硝西泮，你真的用对了吗？

氯硝西泮被称为“最强安眠药”，是我国管制的二类精神药品，具有抗焦虑、催眠及中枢性肌肉松弛作用。氯硝西泮副作用较大，且具有明显的成瘾性和依赖性。氯硝西泮作用于中枢神经系统的苯二氮卓受体（BZR），加强中枢抑制性神经递质 γ-氨基丁酸（GABA）与 GABAA 受体的结合，促进氯通道开放，细胞过极化，增强 GABA 能神经元所介导的突触抑制，使神经元的兴奋性降低。临床可用于治疗如下疾病：癫痫发作、惊恐障碍、焦虑状态和失眠。国内外指南推荐可点击图片查看氯硝西泮常见不良反应可点击图片查看患者用药注意1.患者应避免进行需要精神警觉性或协调性的活动，直至药效得以实现2.建议长期用药的患者勿突然停药，以避免出现戒断症状3.患者服用该药时勿饮酒特殊人群用药注意事项老年人用药：老年人对长效苯二氮䓬类安眠药如地西泮、氯硝西泮等敏感性高，代谢慢，更易发生宿醉效应，故该类药物在老年人中需谨慎应用；孕妇用药：根据FDA分级，苯二氮䓬类药物中艾司唑仑为X级，硝西泮为C级，其他均为D及；非苯二氮䓬类药物中，扎来普隆、唑吡坦、佐匹克隆及右佐匹克隆均为C级。孕妇用药需谨慎。综上，氯硝西泮属于中效苯二氮卓类镇静催眠药，过去临床上常用其治疗失眠症，尤其适用于睡眠维持障碍的患者，但由于其不良反应多且发生率高，目前临床上很少用其治疗失眠症，如今，氯硝西泮在临床上主要用于控制各型癫痫发作，因此，开具氯硝西泮时应结合患者情况进行评估是否试用。参考资料：[1] 氯硝西泮说明书[2] 中华医学会神经病学分会, 中华医学会神经病学分会睡眠障碍学组, 中华医学会神经病学分会神经心理与行为神经病学学组. 中国成人失眠伴抑郁焦虑诊治专家共识 [J]. 中华神经科杂志,2020,53(08)：564-574[3] 中华医学会神经病学分会睡眠障碍学组. 中国快速眼球运动睡眠期行为障碍诊断与治疗专家共识 [J]. 中华神经科杂志,2017,50(8)：567-571.[4] 中华预防医学会更年期保健分会, 中国人体健康科技促进会妇科内分泌和生育力促进专委会, 北京中西医结合学会更年期专业委员会. 绝经相关失眠临床管理中国专家共识 [J]. 中国全科医学,2023,26(24)：2951-2958.[5] 中国睡眠研究会. 中国失眠症诊断和治疗指南 [J]. 中华医学杂志,2017,97(24)：1844-1856.[6] 中国医师协会全科医师分会双心学组, 心血管疾病合并失眠诊疗中国专家共识组. 心血管疾病合并失眠诊疗中国专家共识 [J]. 中华内科杂志,2017,56(4)：310-315.[7]《安眠药的分类及选择丨协和神经科基本功》，作者北京协和医院史佳宇编辑 | B.O如有侵权请联络梅斯医学管理员王晓亮@梅斯医学（微信号：wxid_vaci8ymoetvp22）“鬼压床”究竟是怎么回事？经常被“压”的人要小心了！注意！这10个常见焦虑症状不可忽视，你的胃可能在诉说......警惕！这类家属可能会对精神病患者造成严重影响！↓点击下方“阅读原文”，下载梅斯医学APP吧！

100 项与硝西泮相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
D00531	硝西泮	N05CD02	DB01595

研发状态

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
麻醉	日本	Kyowa Pharmaceutical Industry Co., Ltd.	1967-02-25
强直阵挛性癫痫	日本	Kyowa Pharmaceutical Industry Co., Ltd.	1967-02-25
癫痫	-	-	1965-01-01
入睡和睡眠障碍	-	-	1965-01-01

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


NCT00707915 (CTgov)	临床4期	药物不良反应	30	benzodiazepine	蓋艱簾鑰廠構膚夢願選(蓋鬱顧襯鑰憲積範廠網) = 選簾獵構壓夢選繭襯鏇餘遞獵醖醖繭淵蓋積範 (夢願齋願窪淵繭齋餘襯, 壓憲鹹蓋餘齋齋夢鏇繭 ~ 醖觸鏇顧鹹壓衊淵鑰壓) 更多	-	2012-03-26