甲磺酸非诺多泮(Fenoldopam Mesylate) - 药物靶点：ADRA2 x D1 receptor_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Fenoldopam、Fenoldopam mesylate (USP)

+ [8]

靶点

ADRA2 x D1 receptor

作用机制

ADRA2激动剂(肾上腺素能受体α-2家族激动剂)、D1 receptor激动剂(多巴胺D1受体激动剂)

治疗领域

心血管疾病泌尿生殖系统疾病

在研适应症-

非在研适应症

急性肾损伤心脏病高血压+ [2]

原研机构

Abbott Laboratories

在研机构-

非在研机构

扬子江药业集团北京海燕药业有限公司

Hospira, Inc.

Abbott Laboratories

最高研发阶段撤市

首次获批日期

美国 (1997-09-23),

恶性高血压高血压

最高研发阶段(中国)暂停

特殊审评-

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结构/序列

分子式C17H20ClNO6S

InChIKeyCVKUMNRCIJMVAR-UHFFFAOYSA-N

CAS号67227-57-0

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关联

21

项与甲磺酸非诺多泮相关的临床试验

NCT02620761

/ Terminated临床2/3期IIT

Fenoldopam to Prevent Renal Dysfunction in Indomethacin Treated Preterm Infants

The investigators will conduct a prospective, blinded, randomized, placebo-controlled trial with a sample size of 20 patients in each of the two arms (fenoldopam vs placebo) based upon a difference in serum creatinine by one standard deviation. Fluid and salt intake will be held constant within clinical parameters and carefully measured. Fenoldopam will be started at 0.1 ug/kg/min. If, after 6 hrs there is no decrease in blood pressure, the dose will be increased to 0.2 ug/kg/min. This dose will be continued throughout the remainder of the study. A study of pediatric patients previously provided to the FDA showed no hypotension at a dose of 0.2 ug/kg/min. Fenoldopam will be started 12 hrs before the first dose of indomethacin and discontinued 12 hrs after the 3rd dose of indomethacin. Study samples will include both blood and urine. The primary outcome will be a reduction in renal dysfunction, as determined by creatinine and urine output over the course of treatment. Additional outcomes will include determination of known and novel metabolomic urine markers of renal dysfunction.

开始日期2019-02-06

申办/合作机构

Medical College of Wisconsin

CTR20131661

/ Completed临床1期

甲磺酸非诺多泮注射液在高血压患者的人体药代动力学试验

以高血压患者舒张压降低值来评价药物的线性关系，估算非诺多泮主要药代动力学参数。

开始日期2013-11-05

申办/合作机构

扬子江药业集团北京海燕药业有限公司

CTR20130438

/ Completed临床2期

甲磺酸非诺多泮注射液治疗高血压急症的随机、单盲、阳性药平行对照、多中心临床试验

以注射用硝普钠为对照，评价甲磺酸非诺多泮注射液治疗高血压急症的有效性和安全性。

开始日期2012-09-04

申办/合作机构

扬子江药业集团北京海燕药业有限公司

100 项与甲磺酸非诺多泮相关的临床结果

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100 项与甲磺酸非诺多泮相关的转化医学

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100 项与甲磺酸非诺多泮相关的专利（医药）

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809

项与甲磺酸非诺多泮相关的文献（医药）

2025-01-01·Pediatric Nephrology

Efficacy and safety of fenoldopam for the treatment of hypertensive crises in children with kidney disease: a retrospective study

Article

作者: Vigezzi, Serena ; Vidal, Enrico ; Meneghesso, Davide ; Daverio, Marco ; Tinnirello, Matteo ; Bertazza Partigiani, Nicola ; Brazzale, Alessandra Rosalba

AbstractBackgroundHypertensive crises in children represent critical medical situations characterized by severe hypertension and potential organ damage. Fenoldopam, a dopaminergic medication, offers a viable therapeutic option for managing such clinical scenarios. We aimed to evaluate efficacy and safety of fenoldopam in the management of hypertensive urgencies and emergencies.MethodsThis retrospective analysis focused on pediatric patients affected by acute or chronic kidney disease, aged 1 month–18 years, admitted to the Pediatric Nephrology and the Pediatric Intensive Care Unit at University-Hospital of Padua, Italy, who presented with a hypertensive crisis treated with fenoldopam between March 2010 and December 2022.ResultsThe study included 74 patients with median age 10 years (interquartile range [IQR] 4–15 years) who received 102 fenoldopam infusions. Seventy-two percent were already receiving antihypertensive treatment before admission. In all cases, fenoldopam was associated with a reduction of blood pressure (BP) after 8 h of treatment, but in 87% of patients reduction of the initial mean arterial pressure (MAP) was higher than 25% of calculated drop pressure. MAP normalized in 26% of cases after 24 h and in 35% after 48 h. Occurrence of hypotension was 7%, while hypokalemia was observed in 13% of cases. Patients who presented a MAP reduction not exceeding 25% of calculated drop pressure received a lower median fenoldopam dose (0.2 mcg/kg/min; IQR 0.1–0.2) compared with patients having a MAP reduction > 25% of calculated drop pressure (0.4 mcg/kg/min; IQR 0.2–0.6; p = 0.002).ConclusionsFenoldopam seems effective and safe for the treatment of hypertensive crises in children with kidney disease, at a starting dose of 0.2 mcg/kg/min. Strict BP monitoring is required to identify possible excessive drop pressure in the first hours of infusion.Graphical abstract

2024-12-01·Kidney International

Chronic endothelial dopamine receptor stimulation improves endothelial function and hemodynamics in autosomal dominant polycystic kidney disease

Article

作者: Hamzaoui, Mouad ; Joannidès, Robinson ; Dumesnil, Anaïs ; Arndt, Hans-Dieter ; Renet, Sylvanie ; Lévêque, Emilie ; Richard, Vincent ; Audrézet, Marie-Pierre ; Remy-Jouet, Isabelle ; Enzensperger, Christoph ; Brunel, Valéry ; Bellien, Jérémy ; Dumont, Audrey ; Groussard, Déborah ; Bertrand, Dominique ; Iacob, Michèle ; Hanoy, Mélanie ; Chevalier, Laurence ; Le Roy, Frank ; Guerrot, Dominique ; Duflot, Thomas ; Michel-Després, Aurore

Altered polycystin-mediated endothelial flow mechanosensitivity contributes to the development of hypertension and cardiovascular complications in patients with autosomal dominant polycystic kidney disease (ADPKD). Stimulation of endothelial type 5 dopamine receptors (DR5) can acutely compensate for the endothelial consequences of polycystin deficiency, but the chronic impact of this approach must be evaluated in ADPKD. Nineteen patients with ADPKD on standard of care therapy were randomized to receive a 2-month treatment with the DR agonist rotigotine using transdermal patches, nine at 2 mg/24hours and ten at 4 mg/24hours or while ten were untreated. Rotigotine at the dose of 4 mg/24hours significantly increased nitric oxide release (nitrite levels from 10±30 to 46±34 nmol/L) and radial artery endothelium-dependent flow-mediated dilatation (from 16.4±6.3 to 22.5±7.3%) in response to hand skin heating. Systemic hemodynamics were not significantly modified but aplanation tonometry showed that rotigotine at 4 mg/24hours reduced aortic augmentation index and pulse pressure without affecting carotid-to femoral pulse wave velocity. Plasma creatinine and urea, urinary cyclic AMP, which contributes to cyst growth in ADPKD and copeptin, a surrogate marker of vasopressin, were not affected by rotigotine. In mice with a specific deletion of polycystin-1 in endothelial cells, chronic infusion of the peripheral DR5 agonist fenoldopam also improved mesenteric artery flow-mediated dilatation and reduced blood pressure. Thus, our study demonstrates that in patients with ADPKD, chronic administration of rotigotine improves conduit artery endothelial function through the restoration of flow-induced nitric oxide release as well as hemodynamics suggesting that endothelial DR5 activation may represent a promising pharmacological approach to prevent cardiovascular complications of ADPKD.

2024-08-12·Journal of Biomolecular Structure and Dynamics

Computational screening and MM/GBSA-based MD simulation studies reveal the high binding potential of FDA-approved drugs against Cutibacterium acnes sialidase

Article

作者: Raza, Khalid ; Gautam, Hemant K ; Ahmad, Shaban ; Singh, Akash Pratap

Cutibacterium acnes is an opportunistic pathogen linked with acne vulgaris, affecting 80-90% of teenagers globally. On the leukocyte (WBCs) cell surface, the cell wall anchored sialidase in C. acnes virulence factor, catalysing the sialoconjugates into sialic acids and nutrients for C. acnes resulting in human skin inflammation. The clinical use of antibiotics for acne treatments has severe adverse effects, including microbial dysbiosis and resistance. Therefore, identifying inhibitors for primary virulence factors (Sialidase) was done using molecular docking of 1030 FDA-approved drugs. Initially, based on binding energies (ΔG), Naloxone (ZINC000000389747), Fenoldopam (ZINC000022116608), Labetalol (ZINC000000403010) and Thalitone (ZINC000000057255) were identified that showed high binding energies as -10.2, -10.1, -9.9 and -9.8 kcal/mol, respectively. In 2D analysis, these drugs also showed considerable structural conformer of hydrogen and hydrophobic interactions. Further, a 100 ns MD simulation study found the lowest deviation and fluctuations with various intermolecular interactions to stabilise the complexes. Out of 4, the Naloxone molecule showed robust, steady, and stable RMSD 0.23 ± 0.18 nm. Further, MMGBSA analysis supports MD results and found strong binding energy (ΔG) -29.71 ± 4.97 kcal/mol. In Comparative studies with Neu5Ac2en (native substrate) revealed naloxone has a higher affinity for sialidase. The PCA analysis showed that Naloxone and Thalitone were actively located on the active site, and other compounds were flickered. Our extensive computational and statistical report demonstrates that these FDA drugs can be validated as potential sialidase inhibitors.Communicated by Ramaswamy H. Sarma.

1

项与甲磺酸非诺多泮相关的新闻（医药）

2023-08-24

·米内网

【关注】24个儿科药鼓励研发，南京正大天晴、扬子江......

精彩内容8月23日，国家卫健委发布“第四批鼓励研发申报儿童药品清单”，24个药品位列其中。经梳理，有23个儿科药未在国内获批，但已有多家企业展开布局，包括雷美替胺片剂、非诺多泮注射剂、培妥罗凝血素α注射剂等，涉及南京正大天晴药业、扬子江药业、诺和诺德等多家药企。来源：国家卫健委官网对比今年5月公示的“第四批鼓励研发申报儿童药品建议清单”，氯法拉滨注射剂、匹莫齐特片剂、卡培立肽粉针剂、纳多洛尔片剂、托氟沙星颗粒剂5个产品在正式名单中被剔除。第四批鼓励研发申报儿童药品清单来源：国家卫健委、米内网综合数据库24个纳入第四批鼓励研发申报的儿科药中，有12个为注射剂，占比50%；混悬剂（3个）、溶液剂（2个）及片剂（2个）分别位居其后。从治疗大类看，消化系统及代谢药占据主导，有6个药品上榜；神经系统药物、抗肿瘤和免疫调节剂、皮肤病用药、血液和造血系统药物和全身用激素类制剂（不含性激素）占4、3、2、2、2个。其中，雷美替安最初由日本武田制药开发，于2005年获美国FDA批准上市，是全球首个用于临床治疗失眠的褪黑素受体激动剂，米内网数据显示，该药2022年全球销售额约87亿日元。目前在国内，南京正大天晴药业的雷美替胺片（仿制3类）正处于临床试验阶段。非诺多泮属于特异性DA受体激动剂，同时具备降低动脉压、促尿钠排泄和利尿等特性，特别适用于严重高血压的紧急短期处理，扬子江药业正针对该产品的高血压急症开展临床试验。高血压用药为扬子江重点布局领域，目前已有近20款相关产品获批上市，其中氨氯地平贝那普利胶囊、盐酸索他洛尔注射液等为独家品种。米内网数据显示，2022年中国三大终端六大市场（统计范围详见本文末）高血压用药市场规模接近700亿元。近年来中国三大终端六大市场高血压用药销售趋势（单位：万元）来源：米内网格局数据库此外，Immedica的苯丁酸甘油酯口服溶液剂于今年7月获批上市，健赞的艾夫糖苷酶α注射剂、礼来的高血糖素鼻用散剂、Medice Arzneimittel Pütter的哌甲酯缓释胶囊已报产在审，阿斯利康的阿伏利尤单抗注射剂、Marinus的加那索龙混悬剂、诺和诺德的培妥罗凝血素α注射剂等5个产品已进入Ⅲ期临床。资料来源：米内网数据库、国家卫健委官网注：米内网《中国三大终端六大市场药品竞争格局》，统计范围是：城市公立医院和县级公立医院、城市社区中心和乡镇卫生院、城市实体药店和网上药店，不含民营医院、私人诊所、村卫生室，不含县乡村药店；上述销售额以产品在终端的平均零售价计算。数据统计截至8月24日，如有疏漏，欢迎指正！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

上市批准临床3期

100 项与甲磺酸非诺多泮相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D00613	甲磺酸非诺多泮	C01CA19	DB00800

研发状态

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
急性肾损伤	临床2期	-	Abbott Laboratories	2002-05-01
心脏病	临床2期	-	Abbott Laboratories	2002-05-01
终末期肾脏病	临床2期	-	Abbott Laboratories	2002-05-01
高血压	临床1期	美国	Hospira, Inc.	1997-09-23

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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


NCT00122018 \| NCT00621790 \| NCT00557219 \| NCT00747331 \| NCT02620761 \| NCT00286403 \| NCT00467181 \| NCT00982527 \| NCT01073189 \| NCT00743106 \| NCT01690832 (Pubmed \| Cochrane Database Syst Rev)	N/A	急性肾损伤	3,339	Fenoldopam	鏇壓齋衊糧憲選襯淵齋(鏇遞壓膚艱蓋廠積顧衊) = It is uncertain whether adverse events (hypotension, myocardial infarction, drug intolerance, cardiac arrhythmias) differed between the treatment groups as the certainty of the evidence was very low. 鬱築顧鏇鏇鬱膚網鬱襯 (鹽願衊窪獵膚積積蓋襯 ) 更多	积极	2024-11-28
NCT02620761 (Fenaki, CTgov)	临床2/3期	动脉导管未闭 \| 急性肾损伤	1	0.9%NS (Control)	襯網鑰範艱蓋廠夢糧選(齋簾夢廠觸壓選淵鏇範) = 壓壓積鏇願醖觸遞觸壓蓋繭構繭範蓋蓋壓醖憲 (構簾顧餘艱夢顧壓製淵, 積簾願簾醖顧膚築築壓 ~ 獵簾襯鏇築顧鏇願襯夢) 更多	-	2022-09-16
				Fenoldopam (Fenoldopam)	襯網鑰範艱蓋廠夢糧選(齋簾夢廠觸壓選淵鏇範) = 鹹蓋觸鬱壓顧壓鏇膚鑰蓋繭構繭範蓋蓋壓醖憲 (構簾顧餘艱夢顧壓製淵, 醖醖蓋顧願夢構壓鏇鹹 ~ 淵簾齋鹹夢網願齋壓顧) 更多
NCT00743106 (CTgov)	N/A	肾病	90	Placebo (Placebo)	艱餘蓋鹹構糧顧範築獵(糧鏇網醖築網鹹鏇築構) = 鑰衊顧餘選簾餘製鏇鹹簾蓋鬱壓遞範窪襯窪網 (蓋艱範蓋獵齋醖壓獵觸, 顧夢齋壓窪糧壓製鏇壓 ~ 衊糧窪艱簾觸廠願積簾) 更多	-	2016-10-31
				Fenoldopam (Fenoldopam)	艱餘蓋鹹構糧顧範築獵(糧鏇網醖築網鹹鏇築構) = 憲簾餘窪膚築範鬱糧獵簾蓋鬱壓遞範窪襯窪網 (蓋艱範蓋獵齋醖壓獵觸, 襯衊築餘繭廠壓鏇艱鏇 ~ 蓋觸鏇鹹衊窪積鹽壓製) 更多
NCT00621790 (Pubmed \| JAMA)	临床3期	-	667	Fenoldopam	(構顧襯簾齋築鬱願夢膚) = 範襯鏇窪淵繭醖獵糧糧鬱膚淵憲範遞遞淵繭淵 (艱憲糧簾簾繭憲觸鹽遞 )	-	2014-12-03
				Placebo	(構顧襯簾齋築鬱願夢膚) = 鹽選製繭鏇艱壓簾醖範鬱膚淵憲範遞遞淵繭淵 (艱憲糧簾簾繭憲觸鹽遞 )