Delving into the Latest Updates on Metyrosine with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

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

+ [19]

Target

TYH

Action

inhibitors

Mechanism

TYH inhibitors(Tyrosine 3-hydroxylase inhibitors)

Therapeutic Areas

NeoplasmsOther Diseases

Active Indication

Pheochromocytoma

Inactive Indication

DiGeorge SyndromePsychotic Disorders

Originator Organization

Merck Sharp & Dohme Research Laboratories

Active Organization

Bausch Health US LLC

Ono Pharmaceutical Co., Ltd.

Inactive Organization

Bausch Health Americas, Inc.

Drug Highest PhaseApproved

First Approval Date

United States (03 Oct 1979),

Pheochromocytoma

RegulationOrphan Drug (Japan)

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Structure/Sequence

Molecular FormulaC10H13NO3

InChIKeyNHTGHBARYWONDQ-JTQLQIEISA-N

CAS Registry672-87-7

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.

Start Date01 May 2014

Sponsor / Collaborator

Yale University

NCT01127503

/ TerminatedPhase 2

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).

Start Date01 Jun 2010

Sponsor / Collaborator

Bausch Health Americas, Inc.

100 Clinical Results associated with Metyrosine

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100 Translational Medicine associated with Metyrosine

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100 Patents (Medical) associated with Metyrosine

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1,423

Literatures (Medical) associated with Metyrosine

01 Jan 2025·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

Author: 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.

01 Jan 2025·Domestic Animal Endocrinology

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

Article

Author: 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.

01 Jan 2025·Food Frontiers

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

Author: 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 Deals associated with Metyrosine

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External Link

KEGG	Wiki	ATC	Drug Bank
D00762	Metyrosine	C02KB01	DB00765

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Pheochromocytoma	United States	Bausch Health US LLC	03 Oct 1979

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
DiGeorge Syndrome	Preclinical	United States	Bausch Health Americas, Inc.	01 Jun 2010
Psychotic Disorders	Preclinical	United States	Bausch Health Americas, Inc.	01 Jun 2010

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


THU121 (ENDO2023)	Not Applicable	Ascl1+ \| tyrosine hydroxylase \| dopa decarboxylase ... View more	-	Metyrosine	zchcljfsvs(dkqcqcyfmu) = fjqpbzumly yzlnauwltq (cgusayytrt )	-	05 Oct 2023
				Benserazide	zchcljfsvs(dkqcqcyfmu) = euorbgdldd yzlnauwltq (cgusayytrt )
SAT311 (ENDO2023)	Not Applicable	Pheochromocytoma plasma metanephrines \| normetanephrine	-	Metyrosine	xdfaannvdb(ltcehazxch) = gjgqfzpxlc dupmskcznk (qqeccqitst ) View more	-	05 Oct 2023
HOVON-87/NMSG-18 (EHA2019)	Not Applicable	Multiple Myeloma	190	MPR-R	(wipdyvmiop) = zbfbvmrezp ifinhtdiqp (kleetbitfk ) View more	-	15 Jun 2019
				MPT-T	(wipdyvmiop) = pmaxsqlalc ifinhtdiqp (kleetbitfk ) View more
NCT01127503 (CTgov)	Phase 2	DiGeorge Syndrome \| Psychotic Disorders	2	Metyrosine (Metyrosine)	pkbcmbeyuq(bpfqvxuyxe) = hewvipyzcz lxvxwjbxlv (lpfdbgjdjl, rxohdrupqd - sffypboxeh) View more	-	08 May 2018
				Placebo (Placebo)	pkbcmbeyuq(bpfqvxuyxe) = hvmzutoyui lxvxwjbxlv (lpfdbgjdjl, tkozczsabu - twtzveyanr) View more