甲酪氨酸(Metyrosine) - 药物靶点：TYH_在研适应症：嗜铬细胞瘤_专利_临床

概要

基本信息

药物类型

小分子化药

别名

(-)-alpha-Methyl-L-tyrosine、(-)-α-methyl-L-tyrosine、(S)-alpha-Methyltyrosine

+ [19]

靶点

TYH

作用方式

抑制剂

作用机制

TYH抑制剂(酪氨酸-3-羟化酶抑制剂)

治疗领域

肿瘤其他疾病

在研适应症

嗜铬细胞瘤

非在研适应症

迪格奥尔格综合征精神障碍

原研机构

Merck Sharp & Dohme Research Laboratories

在研机构

Bausch Health US LLC

Ono Pharmaceutical Co., Ltd.

非在研机构

Bausch Health Americas, Inc.

最高研发阶段批准上市

首次获批日期

美国 (1979-10-03),

嗜铬细胞瘤

最高研发阶段(中国)-

特殊审评孤儿药 (日本)

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结构/序列

分子式C10H13NO3

InChIKeyNHTGHBARYWONDQ-JTQLQIEISA-N

CAS号672-87-7

关联

3

项与甲酪氨酸相关的临床试验

JPRN-JapicCTI-152999

/ Completed临床1/2期

A multicenter, open-label, uncontrolled, phase 1/2 study and extension study of ONO-5371 for symptoms of pheochromocytoma and paraganglioma caused by excess secretion of catecholamines(ONO-5371-02)

开始日期2015-10-26

申办/合作机构

Ono Pharmaceutical Co., Ltd.

NCT02152670

/ TerminatedN/AIIT

Understanding Dopamine Mechanisms in Cocaine Addiction Using AMPT and Methylphenidate With [11C]RAC/[11C]PHNO PET

Studies using positron emission tomography (PET) have been used with great success in demonstrating specific abnormalities in several facets of dopaminergic system function in human populations (Narendran and Martinez 2009). Among the first, most consistent, and broadly replicated of such findings in drug- (including cocaine) dependent individuals has been the reduction in subcortical (striatal) D2/3 receptors as imaged, most commonly, by the reversible, non-selective, D2/3 receptor antagonist radiotracer, [11C]raclopride. Certain dissociations on D2/3 availability by radioligand ([11C]raclopride vs. [11C]PHNO) and by brain region (striatum vs. SN; terminal vs. somatodendritic, respectively) are poorly understood in relationship to prior antagonist tracer results. In the current study the investigators will use pharmacological interventions (AMPT and methylphenidate) with both antagonist and agonist radiotracers to experimentally reconcile these discordant findings and clarify potential mechanistic inter-relationships.

开始日期2014-05-01

申办/合作机构

Yale University

NCT01127503

/ Terminated临床2期

A Double-Blind, Placebo-Controlled, Multi-Center, Randomized Trial of the Safety and Efficacy of Metyrosine (Demser®) for the Treatment of Psychotic Disorders in Patients With Velo-Cardio-Facial Syndrome

This is an exploratory clinical investigation. The objectives of this study are to evaluate the safety, steady-state pharmacokinetics, and efficacy of metyrosine (Demser®) for the treatment of psychosis in patients with velocardiofacial syndrome (VCFS).

开始日期2010-06-01

申办/合作机构

Bausch Health Americas, Inc.

100 项与甲酪氨酸相关的临床结果

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100 项与甲酪氨酸相关的转化医学

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100 项与甲酪氨酸相关的专利（医药）

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1,423

项与甲酪氨酸相关的文献（医药）

2025-01-01·Domestic Animal Endocrinology

Physiological and metabolic effects of short-term dopamine reduction in healthy horses using a tyrosine hydroxylase inhibitor (alpha-methyl-para-tyrosine)

Article

作者: de Laat, Melody A ; Harris, Patricia A ; Bailey, Simon R. ; Galinelli, Nicolas C. ; Bamford, Nicholas J ; Warnken, Tobias ; Galinelli, Nicolas C ; Erdody, Madison L. ; Erdody, Madison L ; Harris, Patricia A. ; Sillence, Martin N ; Bailey, Simon R ; Bamford, Nicholas J. ; Sillence, Martin N. ; de Laat, Melody A.

Alpha-methyl-para-tyrosine (AMPT) is a reversible inhibitor of tyrosine hydroxylase, the rate-limiting enzyme in catecholamine synthesis. This study aimed to determine whether AMPT could reduce dopamine concentrations in horses. Six healthy adult Standardbred geldings were administered AMPT (40 mg/kg BW, orally) or placebo in a randomised crossover study design. Clinical examination findings were recorded, and blood samples were collected for up to 6 h after administration of AMPT or placebo, for measurement of blood glucose, plasma ACTH and cortisol concentrations, and plasma metabolomic analysis. Plasma prolactin concentration was determined as a proxy index of central dopamine reduction. No adverse clinical effects were detected after oral administration of AMPT, with heart rate, mean arterial pressure and blood glucose concentration not differing between AMPT treatment or placebo. Plasma prolactin concentration peaked 1 h after AMPT administration before returning to baseline at 2 h (for five horses) or 6 h (for one horse). Metabolomic analysis demonstrated a reduction in plasma dopamine (0.72-fold change; P=0.016) 1 h after AMPT treatment. Plasma ACTH and cortisol concentrations were not different between AMPT and placebo over time. A few metabolites associated with ketogenesis were increased, and certain amino acids decreased, at 1 h compared with baseline, for both AMPT treatment and placebo. Therefore, AMPT was effective in reducing both central and circulating dopamine concentrations in healthy horses following a single oral dose. Further pharmacokinetic and pharmacodynamic studies are warranted to optimise the dose and duration of AMPT treatment to achieve longer-term dopamine reduction. Plasma metabolomic findings suggested an interruption to energy flux at the time of sample collection, which may be relevant to nutritional studies in horses and warrants further investigation.

2025-01-01·Domestic Animal Endocrinology

Effect of short-term dopamine reduction on insulin sensitivity and post-prandial insulin and glucose responses in Standardbred horses

Article

作者: de Laat, Melody A ; Harris, Patricia A ; Bailey, Simon R. ; Galinelli, Nicolas C. ; Bamford, Nicholas J ; Warnken, Tobias ; Galinelli, Nicolas C ; Erdody, Madison L. ; Erdody, Madison L ; Harris, Patricia A. ; Sillence, Martin N ; Bailey, Simon R ; Bamford, Nicholas J. ; Sillence, Martin N. ; de Laat, Melody A.

The role of dopamine in the regulation of insulin secretion in horses is poorly understood and requires further investigation. Pituitary pars intermedia dysfunction (PPID) is associated with decreased activity of dopaminergic neurons which normally suppress peptide hormone secretion from the pituitary pars intermedia. A high proportion of horses with PPID also have insulin dysregulation (ID), characterised by post-prandial hyperinsulinaemia and/or tissue insulin resistance, which are risk factors for the development of laminitis. The aim of this study was to investigate the effects of alpha-methyl-para-tyrosine (AMPT), a tyrosine hydroxylase inhibitor that reduces dopamine production, on insulin sensitivity and the post-prandial insulin response to a glucose-containing meal. Six healthy Standardbred horses were enrolled in a placebo-controlled randomised crossover study, in which one dose of AMPT (40 mg/kg BW) or placebo was administered orally, prior to performing an in-feed oral glucose test (OGT) and a frequently sampled intravenous glucose tolerance test (FSIGTT). Dopamine reduction by AMPT was confirmed by an increase in plasma prolactin concentration and the lack of post-prandial increase in plasma dopamine concentration compared to placebo. Post-prandial insulin responses, both peak and AUCi, were increased after AMPT compared to placebo (P=0.048 and P=0.005, respectively), without affecting blood glucose concentrations. However, one dose of AMPT did not appear to affect tissue sensitivity as assessed by the FSIGTT. This study confirmed that dopamine plays a role in the regulation of insulin secretion in horses, as it does in other species, whereby the post-prandial release of dopamine into the circulation may inhibit pancreatic insulin secretion. Further studies are required to evaluate different dosing protocols for AMPT, and to further investigate the links between PPID, ID and laminitis risk in horses.

2025-01-01·Food Frontiers

Acrylamide induces spatiotemporal metabolic profiling disturbance via targeting taurine and hypotaurine metabolism during early zebrafish development

作者: Wu, Yuanzhao ; Wan, Xuzhi ; Zheng, Ruonan ; Zhang, Yu ; Wang, Binjie ; Zhuang, Shulin ; Qin, Yazhou ; Yao, Weixuan ; Zhu, Li ; Song, Xiaoran ; Li, Haoyu ; Zhuang, Pan ; Wang, Anli ; Gao, Yuchen ; Zeng, Jia ; Huang, Yingyu ; Xu, Zhongshi ; Jiao, Jingjing ; Wang, Jiye ; Yao, Jianxin

AbstractAcrylamide, an endocrine‐disrupting emerging contaminant from both the environment and food processing, has been linked to cardiac developmental toxicity in zebrafish. However, the mechanisms involved in the cardiac developmental toxicity from long‐term exposure to acrylamide remain unclear. This study provides in‐depth evidence on the metabolic regulation of zebrafish embryos with acrylamide exposure. A comprehensive metabolites analysis of four different acrylamide exposures (0, 0.5, 1.0, and 2.0 mM) at different zebrafish developmental stages (6, 24, 48, 72, 96, and 120 h post fertilization, hpf) was performed. Metabolite changes throughout the zebrafish development (6–120 hpf) were closely associated with taurine and hypotaurine metabolism. The pattern of significantly changed metabolites revealed that acrylamide strongly disrupts taurine and hypotaurine metabolism related to a deficient cardiovascular system. Moreover, acrylamide exposure disrupted the de novo synthesis of taurine via cysteine sulfinic acid decarboxylase during early zebrafish embryogenesis. In addition, taurine supplementation (10 mM) effectively alleviates acrylamide‐induced deficient cardiovascular system. Our results demonstrate that acrylamide exposure has a detrimental effect on early heart development in zebrafish due to the inhibition of de novo synthesis of taurine.

100 项与甲酪氨酸相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D00762	甲酪氨酸	C02KB01	DB00765

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
嗜铬细胞瘤	美国	Bausch Health US LLC	1979-10-03

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
迪格奥尔格综合征	临床前	美国	Bausch Health Americas, Inc.	2010-06-01
精神障碍	临床前	美国	Bausch Health Americas, Inc.	2010-06-01

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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


THU121 (ENDO2023)	N/A	Ascl1+ \| tyrosine hydroxylase \| dopa decarboxylase ... 更多	-	Metyrosine	顧蓋製願蓋繭糧淵顧繭(襯鏇艱顧醖範醖鏇廠蓋) = 積積鏇選鏇齋憲觸顧範糧夢窪醖鹹構艱築觸廠 (範襯範鏇膚憲膚遞觸網 )	-	2023-10-05
				Benserazide	顧蓋製願蓋繭糧淵顧繭(襯鏇艱顧醖範醖鏇廠蓋) = 艱鑰願廠選廠醖獵廠蓋糧夢窪醖鹹構艱築觸廠 (範襯範鏇膚憲膚遞觸網 )
SAT311 (ENDO2023)	N/A	嗜铬细胞瘤 plasma metanephrines \| normetanephrine	-	Metyrosine	鏇廠鹹築鏇衊構網獵鏇(觸鬱網淵蓋製鹽築構觸) = 範膚鏇窪淵觸壓選蓋蓋淵廠選鏇網憲鏇糧廠壓 (艱艱鏇餘夢鹽蓋願襯鏇 ) 更多	-	2023-10-05
HOVON-87/NMSG-18 (EHA2019)	N/A	多发性骨髓瘤	190	MPR-R	(獵鑰鏇齋壓鬱選醖艱願) = 網構網網憲蓋膚糧構鬱齋遞壓憲膚繭壓選齋糧 (憲廠遞醖淵壓艱構憲餘 ) 更多	-	2019-06-15
				MPT-T	(獵鑰鏇齋壓鬱選醖艱願) = 餘蓋糧鹽蓋鬱鑰積膚鬱齋遞壓憲膚繭壓選齋糧 (憲廠遞醖淵壓艱構憲餘 ) 更多
NCT01127503 (CTgov)	临床2期	迪格奥尔格综合征 \| 精神障碍	2	Metyrosine (Metyrosine)	鹽築遞網範襯艱網鹹鬱(鹹顧顧繭構膚繭構獵範) = 鹽簾糧廠築淵窪範簾淵膚夢淵鬱鹹簾壓蓋艱窪 (壓衊積觸淵願觸鑰繭願, 膚鬱繭鹽遞繭鹹製願憲 ~ 艱構顧窪獵選積窪膚鑰) 更多	-	2018-05-08
				Placebo (Placebo)	鹽築遞網範襯艱網鹹鬱(鹹顧顧繭構膚繭構獵範) = 鬱齋選憲餘選廠繭襯選膚夢淵鬱鹹簾壓蓋艱窪 (壓衊積觸淵願觸鑰繭願, 餘願窪獵鹽鹽簾艱衊簾 ~ 願餘廠鏇夢選觸鑰夢糧) 更多