氢溴酸非诺特罗(Fenoterol Hydrobromide) - 药物靶点：β2-adrenergic receptor_在研适应症：慢性支气管炎，尘肺病，肺气肿_专利_临床

概要

基本信息

药物类型

小分子化药

别名

1-(3,5-dihydroxyphenyl)-1-hydroxy-2-((4-hydroxyphenyl)isopropylamino)ethane、1-(p-hydroxyphenyl)-2-((β-hydroxy-β-(3',5'-dihydroxyphenyl))ethyl)aminopropane、3,5-dihydroxy-α-(((p-hydroxy-α-methylphenethyl)amino)methyl)benzyl alcohol

+ [13]

靶点

β2-adrenergic receptor

作用方式

激动剂

作用机制

β2-adrenergic receptor激动剂(β2-肾上腺素能受体激动剂)

治疗领域

免疫系统疾病感染呼吸系统疾病+ [1]

在研适应症

慢性支气管炎尘肺病肺气肿+ [2]

非在研适应症

慢性肺疾病

原研机构-

在研机构

Nippon Boehringer Ingelheim Co., Ltd.

非在研机构

University Medical Center Göttingen

Boehringer Ingelheim GmbH

权益机构-

最高研发阶段批准上市

首次获批日期

(1971-01-01),

哮喘慢性阻塞性肺疾病

最高研发阶段(中国)-

特殊审评-

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结构/序列

分子式C17H21NO4

InChIKeyLSLYOANBFKQKPT-UHFFFAOYSA-N

CAS号13392-18-2

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关联

8

项与氢溴酸非诺特罗相关的临床试验

ChiCTR2300071384

/ SuspendedN/AIIT

A single center, randomized, open, placebo-controlled, parallel controlled clinical trial on the efficacy and safety of patchouli alcohol in the treatment of acute migraine

开始日期2023-05-22

申办/合作机构

广州医科大学附属第一医院（广州呼吸中心）

NCT05294965

/ Completed早期临床1期IIT

Beta 2 Adrenergic Stimulation vs Cold Exposure to Activate Human Brown Adipose Tissue

The purpose of the study is to asses brown adipose tissue activity in humans after intravenous administration of the selective beta-2-adrenergic agonist fenoterol as compared to the natural activator of brown adipose tissue, a mild cold stimulus.

开始日期2022-04-27

申办/合作机构

Universitätsspital Basel

NCT03910985

/ Unknown status临床4期IIT

Assessment of Reactance Parameters Measured by the Forced Oscillation Technique for the Bronchodilator Response in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

The aims of this study is :
to assess the bronchodilator (DUOVENT HFA) response of parameters measured by the forced oscillations (FOT) and in particular the reactance parameters related to the presence of a limitation of expiratory flows
to compare the response of the reactance parameters to bronchodilators with the conventional spirometric parameters (FEV1) and inspiratory capacity (IC), and according to the severity of the disease
to assess and compare the relationship between the response to bronchodilators in terms of IC on the one hand and on the other hand in terms of FEV1, reactance parameters (measured by FOT), resistance parameters (measured by plethysmography and FOT)
Assess and compare the relationship between dyspnea intensity assessed by various scales and conventional respiratory function parameters (spirometry, plethysmography, diffusion indices) and parameters measured by FOT

开始日期2019-04-23

申办/合作机构-

100 项与氢溴酸非诺特罗相关的临床结果

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100 项与氢溴酸非诺特罗相关的转化医学

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100 项与氢溴酸非诺特罗相关的专利（医药）

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2,699

项与氢溴酸非诺特罗相关的文献（医药）

2025-04-01·Journal of Biological Chemistry

Substrate-specific effects point to the important role of Y361 as part of the YER motif in closing the binding pocket of OCT1

Article

作者: Neumann, Anna ; Lazzarin, Erika ; Stockner, Thomas ; Lindemann, Erik ; Meyer-Tönnies, Marleen J ; Tzvetkov, Mladen V ; Römer, Sarah

Organic cation transporter 1 (OCT1) is located in the sinusoidal membrane of human hepatocytes. It mediates the uptake of hydrophilic organic cationic drugs in hepatocytes and thus determine their systemic concentrations. OCT1 has a broad spectrum of structurally diverse substrates like metformin, sumatriptan, trospium, and fenoterol. Recent cryo-EM data suggested that Y361 (tyrosine₃₆₁), E386 (glutamate₃₈₆), and R439 (arginine₄₃₉), referred to as the YER motif, could be important for transport. Building on this, we used extensive functional analyses to investigate the general function and the substrate-specific effects of the YER motif. We determined the activity of the Y361A, E386A, and R439A mutants for 15 OCT1 substrates. Extended mutagenesis revealed the negative charge of E386 and the positive charge of R439 as essential for the transport of all substrates tested. Charge reversal mutants, E386R-R439E, did not restore transport activity, suggesting that at least one of the two amino acids is involved in additional interactions essential for transport. Y361 exhibited substrate-specific effects. The Y361A mutant transported fenoterol but not pirbuterol or other beta₂-adrenergic drugs with only one aromatic ring. Molecular dynamics simulations suggested that substrates with aromatic or lipophilic characteristics may compensate for the missing aromatic ring at position 361. Only tryptophan at codon 361 efficiently rescued the transport of the Y361A mutant supporting hydrogen bound interaction with E386 and R439. Our study confirms that the YER motif is essential for OCT1 transport and points to Y361 as a lever that interacts with E386 and R439 to trigger the closing of the binding pocket of human OCT1.

2025-03-01·Journal of Pharmaceutical and Biomedical Analysis

Plasma metabolomic signatures after oral administration of ritonavir in COVID-19 treatment via chemometrics-assisted UPLC/Q-TOF/MS/MS

Article

作者: Gundogdu, Gulsah ; Demir, Sema Nur ; Kadioglu, Yucel ; Abd El-Aty, A M ; Yuksel, Busra ; Bayrak, Burak ; Demirkaya Miloglu, Fatma

Understanding the pharmacodynamics of ritonavir through metabolomics offers insights into its side effects and helps in the development of safer therapies. This study aimed to investigate the effects of ritonavir treatment on the metabolic profiles of rabbits via a metabolomics approach, with the objective of elucidating its impact on various biochemical pathways and identifying relevant biomarkers. The rabbits were divided into control and ritonavir-treated groups, and their plasma samples were analyzed via ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF/MS/MS). Metabolites were identified on the basis of the masscharge ratio (m/z) and validated via XCMS software. Metabolites with a fold change ≥ 1.5 and P ≤ 0.01 were analyzed via principal component analysis (PCA) and orthogonal partial least squares discrimination analysis (OPLS-DA) to distinguish between the groups. MetaboAnalyst 6.0 was used for pathway analysis to identify metabolic pathways affected by ritonavir. The PCA and OPLS-DA models revealed clear separation between the control and ritonavir-treated groups, with high R² and Q² values indicating robust model performance. Pathway analysis revealed that ritonavir treatment significantly affected several metabolic pathways, including those related to ether lipid, phenylalanine, sphingolipid, and glycerophospholipid metabolism. Particularly significant changes were observed in metabolites related to lipid metabolism, oxidative stress responses and cellular signaling. Ritonavir significantly impacts metabolic pathways, particularly those involved in lipid metabolism, and oxidative stress responses, which may influence immune responses and drug interactions. This study also highlights the potential of integrating metabolomics with personalized medicine approaches to optimize ritonavir treatment strategies and reduce adverse effects. These findings indicate that ritonavir significantly influences cellular homeostasis and metabolic processes in addition to its antiviral properties. This highlights the necessity of comprehending the metabolic effects of ritonavir to enhance its clinical application, especially in the management of COVID-19. Further research is warranted to explore these alterations and their implications for therapeutic strategies.

2025-02-01·Analytical and Bioanalytical Chemistry

LC-HRMS screening procedure for the detection of 11 different classes of prohibited substances in dried urine spots for doping control purposes

Article

作者: Van Eenoo, Peter ; Pizzolato, Francesca ; Honesová, Lenka ; Gmeiner, Günter ; Tsivou, Maria ; Mazzarino, Monica

Dried urine spots have recently been proposed as an alternative matrix in the anti-doping field. Drying urine may open the opportunity to limit microbial and thermal degradation of the prohibited substances during transportation to the anti-doping laboratories without the need for refrigeration or freezing. In this study, a multi-targeted initial testing procedure was developed for the determination of 237 prohibited drugs/metabolites from 11 different classes in dried urine spots. The comparability between two different microsampling techniques (i.e., Whatman^® FTA DMPK-C cards and Mitra^® tips) was evaluated. The developed method was then used to evaluate the stability of the target compounds in urine for 7 days under different environmental conditions to simulate the transportation of the urine samples from the collection sites to anti-doping laboratories. Sample preparation consists of (i) extraction of the analytes from the collection device using a mixture of acetonitrile/methanol (1/1) for 30 min at 40 °C, (ii) enzymatic hydrolysis, and (iii) sample concentration by solid-phase extraction. Analysis was performed using liquid chromatography coupled to high-resolution mass spectrometry. The entire workflow was validated in terms of specificity (analytes were distinguishable from the matrix interferences), sensitivity (only with the Mitra^® tips the limits of detection comply with the World Anti-Doping Agency's requirements for the majority of the target compounds), carry-over (no signals in the negative urine injected after the positive urine), matrix effect (16-28% for Mitra^® tips and 22-35% for DMPK-C cards), and extraction yield (Mitra^® tips: 51-88%; DMPK-C cards: 40-76%). As proof of concept, authentic urine samples were analyzed: results obtained in dried urine were compared with those of fluid urine, providing good agreement. Stability studies showed that the target compounds were stable for the whole duration of the study (7 days) at -20 and 4 °C in both fluid and dried urine. At 50 °C or at 20-25 °C, several thiazide-based compounds were completely degraded to their degradation product in the first 24 h or after 3-4 days in fluid urine, whereas in dried urine the compounds were detectable for the entire duration of the study.

100 项与氢溴酸非诺特罗相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D01428	氢溴酸非诺特罗	R03AC04 G02CA03 R03CC04	DB01288

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
慢性支气管炎	日本	Nippon Boehringer Ingelheim Co., Ltd.	1999-03-15
尘肺病	日本	Nippon Boehringer Ingelheim Co., Ltd.	1999-03-15
肺气肿	日本	Nippon Boehringer Ingelheim Co., Ltd.	1999-03-15
哮喘	-	-	1971-01-01
慢性阻塞性肺疾病	-	-	1971-01-01

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
哮喘	临床2期	-	Boehringer Ingelheim GmbH	1990-02-01
慢性肺疾病	临床1期	荷兰	Boehringer Ingelheim GmbH	2002-10-01
慢性阻塞性肺疾病	临床1期	荷兰	Boehringer Ingelheim GmbH	2002-10-01

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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


ERS2014	N/A	阻塞性肺疾病	42	Fenoterol	(選繭範夢積範襯鑰襯鹹) = 鹹膚窪糧簾醖選衊選醖餘鬱獵衊積廠齋鬱糧夢 (夢選壓鹽壓鹹醖膚積齋 )	积极	2014-09-01
				Ipratropium	(選繭範夢積範襯鑰襯鹹) = 選襯選獵繭鏇壓窪夢製餘鬱獵衊積廠齋鬱糧夢 (夢選壓鹽壓鹹醖膚積齋 )
NCT00274066 (Pubmed \| Chest)	临床3期	慢性阻塞性肺疾病维持 \| 追加	60	Ipratropium bromide	選膚夢鏇蓋觸鹽願願壓(鹹選餘鹹蓋艱願獵選艱) = 醖膚窪襯遞廠製夢膚範築遞繭鹽鹹鑰憲糧鏇襯 (網積製憲齋製構獵壓網 )	-	2007-11-01
				Fenoterol	選膚夢鏇蓋觸鹽願願壓(鹹選餘鹹蓋艱願獵選艱) = 壓觸鹹願襯蓋構簾鑰範築遞繭鹽鹹鑰憲糧鏇襯 (網積製憲齋製構獵壓網 )