METYROSINE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C10H13NO3
Molecular Weight	195.2151
Optical Activity	UNSPECIFIED
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 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pheochromocytoma 14 Sources: https://www.drugs.com/pro/demser.html	Primary		Approved 8429	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 3.07670385E11

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 Co-administed with:: phenytoin(50 mg oral) methoxsalen(10 mg oral) sirolimus(0.5 mg oral) 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 Condition: pancreatic cancer 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 Co-administed with:: phenytoin(50 mg oral) methoxsalen(10 mg oral) sirolimus(0.5 mg oral) 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 Condition: pancreatic cancer 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 Co-administed with:: phenytoin(50 mg oral) methoxsalen(10 mg oral) sirolimus(0.5 mg oral) 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 Condition: pancreatic cancer 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 Co-administed with:: phenytoin(50 mg oral) methoxsalen(10 mg oral) sirolimus(0.5 mg oral) 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 Condition: pancreatic cancer 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 Co-administed with:: phenytoin(50 mg oral) methoxsalen(10 mg oral) sirolimus(0.5 mg oral) 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 Condition: pancreatic cancer 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 Co-administed with:: phenytoin(50 mg oral) methoxsalen(10 mg oral) sirolimus(0.5 mg oral) 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 Condition: pancreatic cancer 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
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
Aaron Chemicals	AR003OHF	http://www.aaronchem.com/672-87-7
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
Alfa Chemistry	AP672877-B	https://reagents.alfa-chemistry.com/product/methyl-l-tyrosine-cas-672-87-7-14903.html
Alfa Chemistry	AP672877-A	https://reagents.alfa-chemistry.com/product/metyrosine-cas-672-87-7-14902.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
CSNpharm	CSN27387	https://www.csnpharm.com/products/metyrosine.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
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
MedChem Express	HY-W015007	https://www.medchemexpress.com/metyrosine.html
Molcore	MC566516	https://www.molcore.com/product/672-87-7
OChem	4270	http://www.ocheminc.com/index.php?act=psearch&pid=672M877
Oakwood	324725	http://www.oakwoodchemical.com/ProductsList.aspx?CategoryID=-2&txtSearch=150021&ExtHyperLink=1
Selleck Chemicals	S5797	http://www.selleckchem.com/products/metyrosine.html
Sigma-Aldrich	M8131_SIGMA	https://www.sigmaaldrich.com/catalog/product/sigma/m8131?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	1443205_USP	https://www.sigmaaldrich.com/catalog/product/usp/1443205?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
abcr GmbH	AB259200	http://www.abcr.com/shop/en/AB259200
mcule	MCULE-5340647798	https://mcule.com/MCULE-5340647798/

PubMed

Title	Date	PubMed
Dieldrin-induced oxidative stress and neurochemical changes contribute to apoptopic cell death in dopaminergic cells.	2001 Dec 1	11728820
Effect of alpha-MPT on imipramine induced antinociception in rats.	2001 Jul	11881581
Effects of alpha-methyl-para-tyrosine-induced catecholamine depletion in patients with seasonal affective disorder in summer remission.	2001 Nov	11682283
Subjective effects of AMPT-induced dopamine depletion in schizophrenia: correlation between dysphoric responses and striatal D(2) binding ratios on SPECT imaging.	2001 Nov	11682247
Involvement of serotonergic and dopaminergic mechanisms in hyperthermia induced by a serotonin-releasing drug, p-chloroamphetamine in mice.	2001 Nov 2	11711040
Schwannoma of the extremities: the role of PET in preoperative planning.	2001 Oct	11685498
I-123-lodo-alpha-methyl tyrosine SPECT in non-parenchymal brain tumours.	2002	12224403
Dopamine autoreceptor regulation of release and uptake in mouse brain slices in the absence of D(3) receptors.	2002	12044470
Dopamine depletion results in increased neostriatal D(2), but not D(1), receptor binding in humans.	2002	11920160
Peripheral 5-HT(2A)-receptor-mediated formation of an inhibitor of atrial natriuretic peptide binding involves inflammation.	2002 Apr 5	11959086
Acetyl-l-carnitine induces muscarinic antinocieption in mice and rats.	2002 Dec	12504925
Effects of pharmacological agents upon a transgenic model of Parkinson's disease in Drosophila melanogaster.	2002 Jan	11752102
Oxidative stress and mitochondrial-mediated apoptosis in dopaminergic cells exposed to methylcyclopentadienyl manganese tricarbonyl.	2002 Jul	12065696
The fetal and neonatal brain protein neuronatin protects PC12 cells against certain types of toxic insult.	2002 Jun 30	12101027
Effects of tyrosine hydroxylase mutants on locomotor activity in Drosophila: a study in functional genomics.	2002 Mar	12036114
Pretreatment evaluation of carcinomas of the hypopharynx and larynx with 18F-fluorodeoxyglucose, 123I-alpha-methyl-L-tyrosine and 99mTc-hexakis-2-methoxyisobutylisonitrile.	2002 Mar	12002706
Effect of depleting vesicular and cytoplasmic dopamine on methylenedioxymethamphetamine neurotoxicity.	2002 Mar	11953446
Monoamine depletion in unmedicated depressed subjects.	2002 Mar 15	11922881
Endocrine effects of centrally injected nociceptin in the rat.	2002 May 31	12031535
The effects of dopamine synthesis inhibitors and dopamine antagonists on regeneration in the hydra Hydra attenuata.	2002 May-Jun	12135343
Modulation of stress-induced and stimulated hyperprolactinemia with the group II metabotropic glutamate receptor selective agonist, LY379268.	2002 Oct	12384165
Interaction of stress and noradrenergic drugs in the control of picrotoxin-induced seizures.	2002 Sep	12350393
Differential effects of amphetamine transport vs. dopamine reverse transport on particulate PKC activity in striatal synaptoneurosomes.	2003 Aug	12740868
Dopamine is involved in selectivity of dopaminergic neuronal death by rotenone.	2003 Dec 19	14663204
Evidence for the involvement of dopamine in ambulation promoted by menthol in mice.	2003 Feb	12686756
Inhibitory effects of atropine and hexamethonium on the angiotensin II-induced contractions of rat anococcygeus smooth muscles.	2003 Feb	12595959
Catecholamines in a macrophage cell line.	2003 Feb	12576223
The L-DOPA-sparing effect of R-(-)-1-(benzofuran-2-yl)-2-propylaminopentane hydrochloride [(-)-BPAP] in reserpine-pretreated rats.	2003 Feb 7	12527038
Prolactin-releasing peptide and its homolog RFRP-1 act in hypothalamus but not in anterior pituitary gland to stimulate stress hormone secretion.	2003 Feb-Mar	12668869
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 Jan	12535622
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 Jun	12823474
Quercetin potentiates L-Dopa reversal of drug-induced catalepsy in rats: possible COMT/MAO inhibition.	2003 Jun	12711835
Overexpression of V-1 prevents nitric oxide-induced cell death: involvement of enhanced tetrahydrobiopterin biosynthesis.	2003 Jun 15	12774312
Regional brain metabolic correlates of alpha-methylparatyrosine-induced depressive symptoms: implications for the neural circuitry of depression.	2003 Jun 18	12813118
Synergistic effect of SCH 58261, an adenosine A2A receptor antagonist, and L-DOPA on the reserpine-induced muscle rigidity in rats.	2003 Mar-Apr	12926542
[Effect of catecholamines synthesis blockade on functional status of hypothalamic vasopressinergic neurons in dehydrated rats].	2003 May-Jun	12973914
Monoamine depletion in psychiatric and healthy populations: review.	2003 Nov	14647394
Sensorimotor deficits in a unilateral intrastriatal 6-OHDA partial lesion model of Parkinson's disease in marmoset monkeys.	2003 Oct	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 Oct	14511126
Gliomatosis cerebri evaluated by 18Falpha-methyl tyrosine positron-emission tomography.	2003 Oct	13680026
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 Oct 23	12972167
Potential mechanisms responsible for chlorotriazine-induced alterations in catecholamines in pheochromocytoma (PC12) cells.	2003 Oct 31	14550852
Neurochemical aspects of susceptibility to depression.	2003 Sep 10	12966120
Parkin gene inactivation alters behaviour and dopamine neurotransmission in the mouse.	2003 Sep 15	12915482
Expression of tyrosine hydroxylase in lymphocytes and effect of endogenous catecholamines on lymphocyte function.	2004	14758053
Postnatal regulation by monoamines of vasopressin expression in the neuroendocrine hypothalamus of MAO-A-deficient mice.	2004 Feb	15009159
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 Feb 6	14746892
Methamphetamine produces neuronal inclusions in the nigrostriatal system and in PC12 cells.	2004 Jan	14675155
Differential effects of local versus systemic angiotensin II in the regulation of leptin release from adipocytes.	2004 Jan	14512436
[Effect of catecholamines on migration and differentiation of gonadotropin releasing hormone-neurons in rats].	2004 Jan-Feb	15027209

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

METYROSINE

Official Name

English

(-)-.ALPHA.-METHYL-L-TYROSINE

Systematic Name

English

METYROSINE [USAN]

Common Name

English

Metirosine [WHO-DD]

Common Name

English

METYROSINE [USP-RS]

Common Name

English

METYROSINE [USP MONOGRAPH]

Common Name

English

RACEMETIROSINE, (S)-

Common Name

English

METYROSINE [ORANGE BOOK]

Common Name

English

METHYLTYROSINE

Systematic 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

METIROSINE

Official Name

English

L-TYROSINE, .ALPHA.-METHYL-, (-)-

Systematic Name

English

L-588357-0

Code

English

METIROSINE [MART.]

Common Name

English

METIROSINE [JAN]

Common Name

English

Classification Tree Code System Code

WHO-ATC

C02KB01