METYROSINE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C10H13NO3
Molecular Weight	195.2151
Optical Activity	( - )
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C[C@](N)(CC1=CC=C(O)C=C1)C(O)=O

InChI

InChIKey=NHTGHBARYWONDQ-JTQLQIEISA-N

InChI=1S/C10H13NO3/c1-10(11,9(13)14)6-7-2-4-8(12)5-3-7/h2-5,12H,6,11H2,1H3,(H,13,14)/t10-/m0/s1

HIDE SMILES / InChI

Description
Sources: http://www.drugbank.ca/drugs/DB00765
Curator's Comment: Description was created based on several sources, including https://www.drugs.com/cdi/metyrosine.html

Metirosine is an antihypertensive drug. Metyrosine inhibits tyrosine hydroxylase, which catalyzes the first transformation in catecholamine biosynthesis, i.e., the conversion of tyrosine to dihydroxyphenylalanine (DOPA). Because the first step is also the rate-limiting step, blockade of tyrosine hydroxylase activity results in decreased endogenous levels of catecholamines and their synthesis. This consequently, depletes the levels of the catecholamines dopamine, adrenaline and noradrenaline in the body,usually measured as decreased urinary excretion of catecholamines and their metabolites. One main end result of the catecholamine depletion is a decrease in blood presure. Metirosine is used for the treatment of patients with pheochromocytoma, for preoperative preparation of patients for surgery, management of patients when surgery is contraindicated, and chronic treatment of patients with malignant pheochromocytoma.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Tyrosine 3-hydroxylase 6 Target ID: CHEMBL1969 Sources: http://www.genome.jp/dbget-bin/www_bget?dr:D00762	Inhibitor 8504

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pheochromocytoma 14 Sources: https://www.drugs.com/pro/demser.html	Primary		Approved 8583	Demser Approved Use Demser is indicated in the treatment of patients with pheochromocytoma for: 1. Preoperative preparation of patients for surgery 2. Management of patients when surgery is contraindicated 3. Chronic treatment of patients with malignant pheochromocytoma. Launch Date 1979

C_max

Value	Dose	Co-administered	Analyte	Population
3313 ng/mL EXPERIMENT http://q4live.s22.clientfiles.s3.amazonaws.com/265040820/files/doc_downloads/scientific-presentations/2019/Phase-II-pharmacokinetics-of-oral-SM-88-in-heavily-pretreated-advanced-pancreatic-ductal-adenocarcinoma-(PC).pdf	230 mg 2 times / day steady-state, oral dose: 230 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		METIROSINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
6550 ng/mL EXPERIMENT http://q4live.s22.clientfiles.s3.amazonaws.com/265040820/files/doc_downloads/scientific-presentations/2019/Phase-II-pharmacokinetics-of-oral-SM-88-in-heavily-pretreated-advanced-pancreatic-ductal-adenocarcinoma-(PC).pdf	920 mg 1 times / day steady-state, oral dose: 920 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		METIROSINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
15538 ng × h/mL EXPERIMENT http://q4live.s22.clientfiles.s3.amazonaws.com/265040820/files/doc_downloads/scientific-presentations/2019/Phase-II-pharmacokinetics-of-oral-SM-88-in-heavily-pretreated-advanced-pancreatic-ductal-adenocarcinoma-(PC).pdf	230 mg 2 times / day steady-state, oral dose: 230 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		METIROSINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
28005 ng × h/mL EXPERIMENT http://q4live.s22.clientfiles.s3.amazonaws.com/265040820/files/doc_downloads/scientific-presentations/2019/Phase-II-pharmacokinetics-of-oral-SM-88-in-heavily-pretreated-advanced-pancreatic-ductal-adenocarcinoma-(PC).pdf	920 mg 1 times / day steady-state, oral dose: 920 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		METIROSINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
9.1 h EXPERIMENT http://q4live.s22.clientfiles.s3.amazonaws.com/265040820/files/doc_downloads/scientific-presentations/2019/Phase-II-pharmacokinetics-of-oral-SM-88-in-heavily-pretreated-advanced-pancreatic-ductal-adenocarcinoma-(PC).pdf	230 mg 2 times / day steady-state, oral dose: 230 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		METIROSINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
4.1 h EXPERIMENT http://q4live.s22.clientfiles.s3.amazonaws.com/265040820/files/doc_downloads/scientific-presentations/2019/Phase-II-pharmacokinetics-of-oral-SM-88-in-heavily-pretreated-advanced-pancreatic-ductal-adenocarcinoma-(PC).pdf	920 mg 1 times / day steady-state, oral dose: 920 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		METIROSINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
920 mg 1 times / day steady, oral Highest studied dose Dose: 920 mg, 1 times / day Route: oral Route: steady Dose: 920 mg, 1 times / day Sources: https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.15_suppl.e15714 https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.4_suppl.200	unhealthy, 64.9 years (range: 45.6 - 84.1 years) Health Status: unhealthy Age Group: 64.9 years (range: 45.6 - 84.1 years) Sources: https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.15_suppl.e15714 https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.4_suppl.200	Other AEs: Arthralgia, Fatigue... Other AEs: Arthralgia (grade 3) Fatigue (grade 3) Asthenia (grade 3) Rash Hypotension Sources: https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.15_suppl.e15714 https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.4_suppl.200

AEs

AE	Significance	Dose	Population
Hypotension		920 mg 1 times / day steady, oral Highest studied dose Dose: 920 mg, 1 times / day Route: oral Route: steady Dose: 920 mg, 1 times / day Sources: https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.15_suppl.e15714 https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.4_suppl.200	unhealthy, 64.9 years (range: 45.6 - 84.1 years) Health Status: unhealthy Age Group: 64.9 years (range: 45.6 - 84.1 years) Sources: https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.15_suppl.e15714 https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.4_suppl.200
Rash		920 mg 1 times / day steady, oral Highest studied dose Dose: 920 mg, 1 times / day Route: oral Route: steady Dose: 920 mg, 1 times / day Sources: https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.15_suppl.e15714 https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.4_suppl.200	unhealthy, 64.9 years (range: 45.6 - 84.1 years) Health Status: unhealthy Age Group: 64.9 years (range: 45.6 - 84.1 years) Sources: https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.15_suppl.e15714 https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.4_suppl.200
Arthralgia	grade 3	920 mg 1 times / day steady, oral Highest studied dose Dose: 920 mg, 1 times / day Route: oral Route: steady Dose: 920 mg, 1 times / day Sources: https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.15_suppl.e15714 https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.4_suppl.200	unhealthy, 64.9 years (range: 45.6 - 84.1 years) Health Status: unhealthy Age Group: 64.9 years (range: 45.6 - 84.1 years) Sources: https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.15_suppl.e15714 https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.4_suppl.200
Asthenia	grade 3	920 mg 1 times / day steady, oral Highest studied dose Dose: 920 mg, 1 times / day Route: oral Route: steady Dose: 920 mg, 1 times / day Sources: https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.15_suppl.e15714 https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.4_suppl.200	unhealthy, 64.9 years (range: 45.6 - 84.1 years) Health Status: unhealthy Age Group: 64.9 years (range: 45.6 - 84.1 years) Sources: https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.15_suppl.e15714 https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.4_suppl.200
Fatigue	grade 3	920 mg 1 times / day steady, oral Highest studied dose Dose: 920 mg, 1 times / day Route: oral Route: steady Dose: 920 mg, 1 times / day Sources: https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.15_suppl.e15714 https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.4_suppl.200	unhealthy, 64.9 years (range: 45.6 - 84.1 years) Health Status: unhealthy Age Group: 64.9 years (range: 45.6 - 84.1 years) Sources: https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.15_suppl.e15714 https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.4_suppl.200

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY566516	https://www.001chemical.com/chem/672-87-7
3B Scientific (Wuhan) Corp	3B3-016953	http://www.3bsc.com/index/pro_info.php?id=39477
AA Blocks	AA003NPN	http://www.aablocks.com/goods/Goods/detail?id=AA003NPN
Aaron Chemicals	AR003OHF	http://www.aaronchem.com/672-87-7
abcr GmbH	AB259200	http://www.abcr.com/shop/en/AB259200
Achemo Scientific Limited	AC-32015	http://www.achemo.com/product_view.asp?ID=36070
Achemo Scientific Limited	AC-32016	http://www.achemo.com/product_view.asp?ID=36071
Achemtek	0104-057683	http://www.achemtek.com/672-87-7
AHH Chemical co.,ltd	MB-00621	http://www.ahhchemical.com/product/MB-00621.html
AHH Chemical co.,ltd	MT-19089	http://www.ahhchemical.com/product/MT-19089.html
AHH Chemical co.,ltd	MT-19091	http://www.ahhchemical.com/product/MT-19091.html
Alfa Chemistry	AP672877-A	https://reagents.alfa-chemistry.com/product/metyrosine-cas-672-87-7-14902.html
Alfa Chemistry	AP672877-B	https://reagents.alfa-chemistry.com/product/methyl-l-tyrosine-cas-672-87-7-14903.html
Alichem	19113893	http://www.alichem.com/en/products/672-87-7.html
Allbio Pharm Co., Ltd	AF12140	http://www.allbiopharm.com/product/n/AF12140
Ambeed	A624425	https://www.ambeed.com/products/672-87-7.html
Ark Pharma Scientific Limited	H-025836	http://www.arkpharmtech.com/product/30889.html
Aurora Fine Chemicals LLC	A17.879.878	http://online.aurorafinechemicals.com/info?ID=A17.879.878
BLD Pharm	BD0208	http://www.bldpharm.com/products/672-87-7.html
Chem Scene	CS-W015723	http://www.chemscene.com/672-87-7.html
Chemenu	CM105103	http://www.chemenu.com/products/CM105103
Chemspace	CSSB00000055778	https://chem-space.com/CSSB00000055778
CSNpharm	CSN27387	https://www.csnpharm.com/products/metyrosine.html
DC Chemicals	DC32913	http://www.dcchemicals.com//product_show-Demser.html
DC Chemicals	DC37508	http://www.dcchemicals.com//product_show-Racemetirosine.html
Enamine	Z1617901128	https://www.enaminestore.com/catalog/Z1617901128
Glentham Life Sciences	GC3195	http://www.glentham.com/products/product/GC3195/
Hairui	HR124153	http://www.hairuichem.com/en/product/658-48-0.html
Lab Network	LN02012307	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN02012307
mcule	MCULE-5340647798	https://mcule.com/MCULE-5340647798/
MedChem Express	HY-W015007	https://www.medchemexpress.com/metyrosine.html
Molcore	MC566516	https://www.molcore.com/product/672-87-7
Oakwood	324725	http://www.oakwoodchemical.com/ProductsList.aspx?CategoryID=-2&txtSearch=150021&ExtHyperLink=1
OChem	4270	http://www.ocheminc.com/index.php?act=psearch&pid=672M877
Selleck Chemicals	S5797	http://www.selleckchem.com/products/metyrosine.html
Sigma-Aldrich	1443205_USP	https://www.sigmaaldrich.com/catalog/product/usp/1443205?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	M8131_SIGMA	https://www.sigmaaldrich.com/catalog/product/sigma/m8131?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Smolecule	S535318	http://www.smolecule.com/products/s535318
Smolecule	S540986	http://www.smolecule.com/products/s540986
Synblock Inc	AB02561	http://www.synblock.com/product/672-87-7.html
THE BioTek	bt-275955	https://www.thebiotek.com/product/inhibitors/bt-275955
THE BioTek	bt-279690	https://www.thebiotek.com/product/inhibitors/bt-279690
W&J PharmaChem	204692	http://www.wjpharmachem.com/new/204692.html
Watanabe Chemical Ind.	J00430	https://www.watanabechem.co.jp/en/search/details.php?code=J00430

PubMed

Title	Date	PubMed
Carnitine palmitoyltransferase-1 (CPT-1) activity stimulation by cerulenin via sympathetic nervous system activation overrides cerulenin's peripheral effect.	2004-07	15044358
[Effect of catecholamines on migration and differentiation of gonadotropin releasing hormone-neurons in rats].	2004-03-19	15027209
Stress- as well as suckling-induced prolactin release is blocked by a structural analogue of the putative hypophysiotrophic prolactin-releasing factor, salsolinol.	2004-03	15049851
Inhibition of dopamine synthesis with alpha-methyl-p-tyrosine abolishes the enhancement of methamphetamine-induced extracellular dopamine levels in the amygdala of rats with excitotoxic lesions of the entorhinal cortex.	2004-02-06	14746892
Postnatal regulation by monoamines of vasopressin expression in the neuroendocrine hypothalamus of MAO-A-deficient mice.	2004-02	15009159
Methamphetamine produces neuronal inclusions in the nigrostriatal system and in PC12 cells.	2004-01	14675155
Differential effects of local versus systemic angiotensin II in the regulation of leptin release from adipocytes.	2004-01	14512436
Expression of tyrosine hydroxylase in lymphocytes and effect of endogenous catecholamines on lymphocyte function.	2004	14758053
Mu opioid control of the N-methyl-D-aspartate-evoked release of [3H]-acetylcholine in the limbic territory of the rat striatum in vitro: diurnal variations and implication of a dopamine link.	2004	14706785
Dopamine is involved in selectivity of dopaminergic neuronal death by rotenone.	2003-12-19	14663204
Comparison of effects of dual transporter inhibitors on monoamine transporters and extracellular levels in rats.	2003-12	14573386
Monoamine depletion in psychiatric and healthy populations: review.	2003-11	14647394
Potential mechanisms responsible for chlorotriazine-induced alterations in catecholamines in pheochromocytoma (PC12) cells.	2003-10-31	14550852
The effect of 3,4-methylenedioxymethamphetamine ('Ecstasy') on serotonergic regulation of the mammalian circadian clock mechanism in rats: the role of dopamine and hyperthermia.	2003-10-23	12972167
Sensorimotor deficits in a unilateral intrastriatal 6-OHDA partial lesion model of Parkinson's disease in marmoset monkeys.	2003-10	14552882
The new neurokinin 1-sensitive receptor mediates the facilitation by endogenous tachykinins of the NMDA-evoked release of acetylcholine after suppression of dopaminergic transmission in the matrix of the rat striatum.	2003-10	14511126
Gliomatosis cerebri evaluated by 18Falpha-methyl tyrosine positron-emission tomography.	2003-10	13680026
[Effect of catecholamines synthesis blockade on functional status of hypothalamic vasopressinergic neurons in dehydrated rats].	2003-09-17	12973914
Parkin gene inactivation alters behaviour and dopamine neurotransmission in the mouse.	2003-09-15	12915482
Neurochemical aspects of susceptibility to depression.	2003-09-10	12966120
Dopamine depletion and in vivo binding of PET D1 receptor radioligands: implications for imaging studies in schizophrenia.	2003-09	12813475
Synergistic effect of SCH 58261, an adenosine A2A receptor antagonist, and L-DOPA on the reserpine-induced muscle rigidity in rats.	2003-08-21	12926542
Differential effects of amphetamine transport vs. dopamine reverse transport on particulate PKC activity in striatal synaptoneurosomes.	2003-08	12740868
Regional brain metabolic correlates of alpha-methylparatyrosine-induced depressive symptoms: implications for the neural circuitry of depression.	2003-06-18	12813118
Overexpression of V-1 prevents nitric oxide-induced cell death: involvement of enhanced tetrahydrobiopterin biosynthesis.	2003-06-15	12774312
Anterograde delivery of brain-derived neurotrophic factor to striatum via nigral transduction of recombinant adeno-associated virus increases neuronal death but promotes neurogenic response following stroke.	2003-06	12823474
Evidence for a monoamine mediated, opioid-independent, antihyperalgesic effect of venlafaxine, a non-tricyclic antidepressant, in a neurogenic pain model in rats.	2003-06	12791429
Quercetin potentiates L-Dopa reversal of drug-induced catalepsy in rats: possible COMT/MAO inhibition.	2003-06	12711835
Prolactin-releasing peptide and its homolog RFRP-1 act in hypothalamus but not in anterior pituitary gland to stimulate stress hormone secretion.	2003-04-02	12668869
Monoaminergic control of vasopressin and VIP expression in the mouse suprachiasmatic nucleus.	2003-03-15	12605405
Modulation of the ability of clozapine to facilitate NMDA- and electrically evoked responses in pyramidal cells of the rat medial prefrontal cortex by dopamine: pharmacological evidence.	2003-03	12670320
The L-DOPA-sparing effect of R-(-)-1-(benzofuran-2-yl)-2-propylaminopentane hydrochloride [(-)-BPAP] in reserpine-pretreated rats.	2003-02-07	12527038
Evidence for the involvement of dopamine in ambulation promoted by menthol in mice.	2003-02	12686756
Inhibitory effects of atropine and hexamethonium on the angiotensin II-induced contractions of rat anococcygeus smooth muscles.	2003-02	12595959
Catecholamines in a macrophage cell line.	2003-02	12576223
Brain tyrosine hydroxylase in the catfish Heteropneustes fossilis: annual and circadian variations, and sex and regional differences in enzyme activity and some kinetic properties.	2003-01	12535622
Effects of catecholamine depletion on D2 receptor binding, mood, and attentiveness in humans: a replication study.	2003-01	12479964
Concomitant effect of acetylcholine and dopamine on carotid chemosensory activity in catecholamine depleted cats.	2003	14635686
Acetyl-l-carnitine induces muscarinic antinocieption in mice and rats.	2002-12	12504925
Catecholamine production and tyrosine hydroxylase expression in peripheral blood mononuclear cells from multiple sclerosis patients: effect of cell stimulation and possible relevance for activation-induced apoptosis.	2002-12	12446028
Noninvasive grading of untreated gliomas: a comparative study of MR imaging and 3-(iodine 123)-L-alpha-methyltyrosine SPECT.	2002-11	12409596
Modulation of stress-induced and stimulated hyperprolactinemia with the group II metabotropic glutamate receptor selective agonist, LY379268.	2002-10	12384165
Interaction of stress and noradrenergic drugs in the control of picrotoxin-induced seizures.	2002-09	12350393
Role of cerebral dopamine but not plasma insulin, leptin and glucocorticoid in the development of tolerance to the anorectic effect of amphetamine.	2002-09	12204294
Neurochemical changes in mice following physical or psychological stress exposures.	2002-08-21	12191822
The effects of dopamine synthesis inhibitors and dopamine antagonists on regeneration in the hydra Hydra attenuata.	2002-07-24	12135343
Oxidative stress and mitochondrial-mediated apoptosis in dopaminergic cells exposed to methylcyclopentadienyl manganese tricarbonyl.	2002-07	12065696
The fetal and neonatal brain protein neuronatin protects PC12 cells against certain types of toxic insult.	2002-06-30	12101027
Effect of catecholamines on activity of Na(+), K(+)-ATPase in neonatal piglet brain during posthypoxic reoxygenation.	2002-05	12062202
I-123-lodo-alpha-methyl tyrosine SPECT in non-parenchymal brain tumours.	2002	12224403

Patents

Sample Use Guides

In Vivo Use Guide

The recommended initial dosage for adults and children 12 years of age and older is 250 mg orally four times daily. This may be increased by 250 mg to 500 mg every day to a maximum of 4.0 g/day in divided doses.

Route of Administration: Oral

In Vitro Use Guide

DA synthesis inhibition (Metirosine, 50 uM) resulted in a marked increase in the firing rates of mouse dopaminergic cells.

Name

Type

Language

METIROSINE

Preferred Name

English

METYROSINE

Official Name

English

(-)-?-Methyl-L-tyrosine

Common Name

English

METYROSINE [USAN]

Common Name

English

L-Tyrosine, ?-methyl-

Common Name

English

Metirosine [WHO-DD]

Common Name

English

METYROSINE [USP-RS]

Common Name

English

METYROSINE [USP MONOGRAPH]

Common Name

English

METYROSINE [ORANGE BOOK]

Common Name

English

Methyltyrosine

Common Name

English

DEMSER

Brand Name

English

MK-781

Code

English

METYROSINE [MI]

Common Name

English

metirosine [INN]

Common Name

English

METYROSINE [VANDF]

Common Name

English

(S)-2-(4-Hydroxybenzyl)-2-aminopropanoic acid

Systematic Name

English

L-Tyrosine, ?-methyl-, (-)-

Common Name

English

L-588357-0

Code

English

(2S)-2-Amino-3-(4-hydroxyphenyl)-2-methylpropanoic acid

Systematic Name

English

METIROSINE [MART.]

Common Name

English

METIROSINE [JAN]

Common Name

English

Classification Tree Code System Code

WHO-ATC

C02KB01