Identification
- Summary
Metyrosine is a tyrosine 3-monooxygenase inhibitor used to treat excessive sympathetic stimulation in pheochromocytoma.
- Brand Names
- Demser
- Generic Name
- Metyrosine
- DrugBank Accession Number
- DB00765
- Background
An inhibitor of the enzyme tyrosine 3-monooxygenase, and consequently of the synthesis of catecholamines. It is used to control the symptoms of excessive sympathetic stimulation in patients with pheochromocytoma. (Martindale, The Extra Pharmacopoeia, 30th ed)
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Metyrosine (DB00765)
- Weight
- Average: 195.2151
Monoisotopic: 195.089543287 - Chemical Formula
- C10H13NO3
- Synonyms
- (-)-alpha-Methyl-L-tyrosine
- (–)-α-methyl-L-tyrosine
- (S)-alpha-Methyltyrosine
- Methyltyrosine
- Metirosin
- Metirosina
- Metirosine
- Métirosine
- Metirosinum
- Metyrosine
- α-methyl-L-p-tyrosine
- α-methyl-p-tyrosine
- α-methyl-para-tyrosine
- α-MPT
- External IDs
- 357 O
- L 588
- L 588357-0
- L-588357-0
- MK 781
- MK-781
Pharmacology
- Indication
For use in 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.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Pheochromocytoma •••••••••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
In patients with pheochromocytoma, who produce excessive amounts of norepinephrine and epinephrine, administration of one to four grams of metyrosine per day has reduced catecholamine biosynthesis from about 35 to 80 percent as measured by the total excretion of catecholamines and their metabolites (metanephrine and vanillylmandelic acid). The maximum biochemical effect usually occurs within two to three days, and the urinary concentration of catecholamines and their metabolites usually returns to pretreatment levels within three to four days after metyrosine is discontinued. Most patients with pheochromocytoma treated with metyrosine experience decreased frequency and severity of hypertensive attacks with their associated headache, nausea, sweating, and tachycardia. In patients who respond, blood pressure decreases progressively during the first two days of therapy with metyrosine; after withdrawal, blood pressure usually increases gradually to pretreatment values within two to three days.
- Mechanism of action
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.
Target Actions Organism ATyrosine 3-monooxygenase binderHumans - Absorption
Well absorbed from the gastrointestinal tract.
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
Little biotransformation, with catechol metabolites accounting for less than 1% of the administered dose.
- Route of elimination
Because the first step is also the rate-limiting step, blockade of tyrosine hydroxylase activity results in decreased endogenous levels of catecholamines, usually measured as decreased urinary excretion of catecholamines and their metabolites.
- Half-life
3.4 to 3.7 hours
- Clearance
Not Available
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Signs of metyrosine overdosage include those central nervous system effects observed in some patients even at low dosages. At doses exceeding 2000 mg/day, some degree of sedation or feeling of fatigue may persist. Doses of 2000-4000 mg/day can result in anxiety or agitated depression, neuromuscular effects (including fine tremor of the hands, gross tremor of the trunk, tightening of the jaw with trismus), diarrhea, and decreased salivation with dry mouth. The acute toxicity of metyrosine was 442 mg/kg and 752 mg/kg in the female mouse and rat respectively.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine 1,2-Benzodiazepine may increase the sedative activities of Metyrosine. Abaloparatide Abaloparatide may increase the hypotensive activities of Metyrosine. Acebutolol Metyrosine may increase the hypotensive activities of Acebutolol. Aceclofenac The therapeutic efficacy of Metyrosine can be decreased when used in combination with Aceclofenac. Acemetacin The therapeutic efficacy of Metyrosine can be decreased when used in combination with Acemetacin. - Food Interactions
- Avoid alcohol. Ingesting alcohol may increase the sedative and CNS depressant effects of metyrosine.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Demser Capsule 250 mg/1 Oral Merck Sharp & Dohme Limited 1979-10-03 2009-05-31 US 
Demser Capsule 250 mg/1 Oral Bausch Health US, LLC 1979-10-03 Not applicable US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Metyrosine Capsule 250 mg/1 Oral Amneal Pharmaceuticals NY LLC 2020-07-24 Not applicable US Metyrosine Capsule 250 mg/1 Oral Amneal Pharmaceuticals NY LLC 2020-07-24 Not applicable US Metyrosine Capsule 250 mg/1 Oral Oceanside Pharmaceuticals 2020-09-07 Not applicable US
Categories
- ATC Codes
- C02KB01 — Metirosine
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as phenylpropanoic acids. These are compounds with a structure containing a benzene ring conjugated to a propanoic acid.
- Kingdom
- Organic compounds
- Super Class
- Phenylpropanoids and polyketides
- Class
- Phenylpropanoic acids
- Sub Class
- Not Available
- Direct Parent
- Phenylpropanoic acids
- Alternative Parents
- D-alpha-amino acids / Amphetamines and derivatives / Phenylpropanes / Aralkylamines / 1-hydroxy-2-unsubstituted benzenoids / Amino acids / Monocarboxylic acids and derivatives / Carboxylic acids / Organopnictogen compounds / Organic oxides show 3 more
- Substituents
- 1-hydroxy-2-unsubstituted benzenoid / 3-phenylpropanoic-acid / Alpha-amino acid / Alpha-amino acid or derivatives / Amine / Amino acid / Amino acid or derivatives / Amphetamine or derivatives / Aralkylamine / Aromatic homomonocyclic compound show 18 more
- Molecular Framework
- Aromatic homomonocyclic compounds
- External Descriptors
- non-proteinogenic L-alpha-amino acid, L-tyrosine derivative (CHEBI:6912)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- DOQ0J0TPF7
- CAS number
- 672-87-7
- InChI Key
- NHTGHBARYWONDQ-JTQLQIEISA-N
- InChI
- 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
- IUPAC Name
- (2S)-2-amino-3-(4-hydroxyphenyl)-2-methylpropanoic acid
- SMILES
- C[C@](N)(CC1=CC=C(O)C=C1)C(O)=O
References
- Synthesis Reference
- US2868818
- General References
- Not Available
- External Links
- Human Metabolome Database
- HMDB0014903
- KEGG Drug
- D00762
- KEGG Compound
- C07921
- PubChem Compound
- 441350
- PubChem Substance
- 46506079
- ChemSpider
- 390103
- 266604
- ChEBI
- 6912
- ChEMBL
- CHEMBL1200862
- ZINC
- ZINC000000000693
- Therapeutic Targets Database
- DAP000471
- PharmGKB
- PA450487
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- %CE%91-Methyl-p-tyrosine
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 2 Active Not Recruiting Treatment Ewing's Sarcoma / Sarcomas 1 2 Terminated Treatment Psychosis / Velo-Cardio-Facial Syndrome 1 Not Available Suspended Diagnostic Bulimia Nervosa / Catechol-O-methyltransferase / Dopamine / Eating Disorders / Reward 1
Pharmacoeconomics
- Manufacturers
- Aton pharma inc
- Packagers
- Aton Pharma Inc.
- Draxis Specialty Pharmaceuticals Inc.
- Merck & Co.
- Dosage Forms
Form Route Strength Capsule Oral 250 mg/1 - Prices
Unit description Cost Unit Demser 250 mg capsule 19.35USD capsule DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 312.5 °C PhysProp water solubility Very slightly soluble Not Available logP -1.7 Not Available - Predicted Properties
Property Value Source Water Solubility 2.48 mg/mL ALOGPS logP -1.9 ALOGPS logP -1.1 Chemaxon logS -1.9 ALOGPS pKa (Strongest Acidic) 2.06 Chemaxon pKa (Strongest Basic) 9.93 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 83.55 Å2 Chemaxon Rotatable Bond Count 3 Chemaxon Refractivity 51.81 m3·mol-1 Chemaxon Polarizability 19.67 Å3 Chemaxon Number of Rings 1 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9918 Blood Brain Barrier - 0.8678 Caco-2 permeable - 0.7026 P-glycoprotein substrate Substrate 0.5286 P-glycoprotein inhibitor I Non-inhibitor 0.9891 P-glycoprotein inhibitor II Non-inhibitor 0.9926 Renal organic cation transporter Non-inhibitor 0.9278 CYP450 2C9 substrate Non-substrate 0.8025 CYP450 2D6 substrate Non-substrate 0.7432 CYP450 3A4 substrate Non-substrate 0.6887 CYP450 1A2 substrate Non-inhibitor 0.9459 CYP450 2C9 inhibitor Non-inhibitor 0.951 CYP450 2D6 inhibitor Non-inhibitor 0.9574 CYP450 2C19 inhibitor Non-inhibitor 0.9116 CYP450 3A4 inhibitor Non-inhibitor 0.892 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9735 Ames test Non AMES toxic 0.9695 Carcinogenicity Non-carcinogens 0.8681 Biodegradation Not ready biodegradable 0.7891 Rat acute toxicity 2.1516 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9852 hERG inhibition (predictor II) Non-inhibitor 0.9728
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-052f-4900000000-946ec0a9cb27d9dde874 Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0002-0900000000-6652807f813af2805df0 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-001u-1900000000-48087192d8178ca8f379 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-001l-9600000000-91800dc45fcc61a7e3bb Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-000x-9500000000-12583b60232daa450d7c Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-001i-1900000000-6a1d86a47a2c97fa7eca Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-004i-9100000000-127a492975d36ac670ff Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 150.4716534 predictedDarkChem Lite v0.1.0 [M-H]- 149.9081534 predictedDarkChem Lite v0.1.0 [M-H]- 138.17018 predictedDeepCCS 1.0 (2019) [M+H]+ 150.0557534 predictedDarkChem Lite v0.1.0 [M+H]+ 150.3057534 predictedDarkChem Lite v0.1.0 [M+H]+ 140.56203 predictedDeepCCS 1.0 (2019) [M+Na]+ 150.1769534 predictedDarkChem Lite v0.1.0 [M+Na]+ 149.9468534 predictedDarkChem Lite v0.1.0 [M+Na]+ 148.10939 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Binder
- General Function
- Tyrosine 3-monooxygenase activity
- Specific Function
- Plays an important role in the physiology of adrenergic neurons.
- Gene Name
- TH
- Uniprot ID
- P07101
- Uniprot Name
- Tyrosine 3-monooxygenase
- Molecular Weight
- 58599.545 Da
References
- Nasrallah HA, Donnelly EF, Bigelow LB, Rivera-Calimlim L, Rogol A, Potkin S, Rauscher FP, Wyatt RJ: Inhibition of dopamine synthesis in chronic schizophrenia. Clinical ineffectiveness of metyrosine. Arch Gen Psychiatry. 1977 Jun;34(6):649-55. [Article]
- Yoshimoto Y, Nakaso K, Nakashima K: L-dopa and dopamine enhance the formation of aggregates under proteasome inhibition in PC12 cells. FEBS Lett. 2005 Feb 14;579(5):1197-202. Epub 2005 Jan 21. [Article]
- Shore PA, Dorris RL: On a prime role for newly synthesized dopamine in striatal function. Eur J Pharmacol. 1975 Feb;30(2):315-8. [Article]
- Moore KE, Demarest KT, Johnston CA: Influence of prolactin on dopaminergic neuronal systems in the hypothalamus. Fed Proc. 1980 Sep;39(11):2912-6. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Drug created at June 13, 2005 13:24 / Updated at December 02, 2023 06:55