Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C10H13NO3.ClH |
| Molecular Weight | 231.676 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
Cl.C[C@](N)(CC1=CC=C(O)C=C1)C(O)=O
InChI
InChIKey=BVYZLEHNLQKCHO-PPHPATTJSA-N
InChI=1S/C10H13NO3.ClH/c1-10(11,9(13)14)6-7-2-4-8(12)5-3-7;/h2-5,12H,6,11H2,1H3,(H,13,14);1H/t10-;/m0./s1
| Molecular Formula | C10H13NO3 |
| Molecular Weight | 195.2151 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
| Molecular Formula | ClH |
| Molecular Weight | 36.461 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
DescriptionSources: http://www.drugbank.ca/drugs/DB00765Curator's Comment: Description was created based on several sources, including
https://www.drugs.com/cdi/metyrosine.html
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.
Originator
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL1969 |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | Demser Approved UseDemser 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 Date1979 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
3313 ng/mL |
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 |
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 |
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 |
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 |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
9.1 h |
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 |
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) Sources: methoxsalen(10 mg oral) sirolimus(0.5 mg oral) |
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: |
Other AEs: Arthralgia, Fatigue... Other AEs: Arthralgia (grade 3) Sources: Fatigue (grade 3) Asthenia (grade 3) Rash Hypotension |
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) Sources: methoxsalen(10 mg oral) sirolimus(0.5 mg oral) |
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: |
|
| 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) Sources: methoxsalen(10 mg oral) sirolimus(0.5 mg oral) |
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: |
|
| 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) Sources: methoxsalen(10 mg oral) sirolimus(0.5 mg oral) |
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: |
| 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) Sources: methoxsalen(10 mg oral) sirolimus(0.5 mg oral) |
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: |
| 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) Sources: methoxsalen(10 mg oral) sirolimus(0.5 mg oral) |
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: |
PubMed
| Title | Date | PubMed |
|---|---|---|
| I-123-lodo-alpha-methyl tyrosine SPECT in non-parenchymal brain tumours. | 2002 |
|
| Neurochemical changes in mice following physical or psychological stress exposures. | 2002 Aug 21 |
|
| Acetyl-l-carnitine induces muscarinic antinocieption in mice and rats. | 2002 Dec |
|
| 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 Dec |
|
| Oxidative stress and mitochondrial-mediated apoptosis in dopaminergic cells exposed to methylcyclopentadienyl manganese tricarbonyl. | 2002 Jul |
|
| The fetal and neonatal brain protein neuronatin protects PC12 cells against certain types of toxic insult. | 2002 Jun 30 |
|
| Effect of catecholamines on activity of Na(+), K(+)-ATPase in neonatal piglet brain during posthypoxic reoxygenation. | 2002 May |
|
| The effects of dopamine synthesis inhibitors and dopamine antagonists on regeneration in the hydra Hydra attenuata. | 2002 May-Jun |
|
| Noninvasive grading of untreated gliomas: a comparative study of MR imaging and 3-(iodine 123)-L-alpha-methyltyrosine SPECT. | 2002 Nov |
|
| Modulation of stress-induced and stimulated hyperprolactinemia with the group II metabotropic glutamate receptor selective agonist, LY379268. | 2002 Oct |
|
| Interaction of stress and noradrenergic drugs in the control of picrotoxin-induced seizures. | 2002 Sep |
|
| Role of cerebral dopamine but not plasma insulin, leptin and glucocorticoid in the development of tolerance to the anorectic effect of amphetamine. | 2002 Sep |
|
| Concomitant effect of acetylcholine and dopamine on carotid chemosensory activity in catecholamine depleted cats. | 2003 |
|
| Differential effects of amphetamine transport vs. dopamine reverse transport on particulate PKC activity in striatal synaptoneurosomes. | 2003 Aug |
|
| Comparison of effects of dual transporter inhibitors on monoamine transporters and extracellular levels in rats. | 2003 Dec |
|
| Dopamine is involved in selectivity of dopaminergic neuronal death by rotenone. | 2003 Dec 19 |
|
| Evidence for the involvement of dopamine in ambulation promoted by menthol in mice. | 2003 Feb |
|
| Inhibitory effects of atropine and hexamethonium on the angiotensin II-induced contractions of rat anococcygeus smooth muscles. | 2003 Feb |
|
| Catecholamines in a macrophage cell line. | 2003 Feb |
|
| The L-DOPA-sparing effect of R-(-)-1-(benzofuran-2-yl)-2-propylaminopentane hydrochloride [(-)-BPAP] in reserpine-pretreated rats. | 2003 Feb 7 |
|
| 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 |
|
| 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 |
|
| Effects of catecholamine depletion on D2 receptor binding, mood, and attentiveness in humans: a replication study. | 2003 Jan |
|
| 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 |
|
| Evidence for a monoamine mediated, opioid-independent, antihyperalgesic effect of venlafaxine, a non-tricyclic antidepressant, in a neurogenic pain model in rats. | 2003 Jun |
|
| Quercetin potentiates L-Dopa reversal of drug-induced catalepsy in rats: possible COMT/MAO inhibition. | 2003 Jun |
|
| Overexpression of V-1 prevents nitric oxide-induced cell death: involvement of enhanced tetrahydrobiopterin biosynthesis. | 2003 Jun 15 |
|
| Regional brain metabolic correlates of alpha-methylparatyrosine-induced depressive symptoms: implications for the neural circuitry of depression. | 2003 Jun 18 |
|
| 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 Mar |
|
| Monoaminergic control of vasopressin and VIP expression in the mouse suprachiasmatic nucleus. | 2003 Mar 15 |
|
| Synergistic effect of SCH 58261, an adenosine A2A receptor antagonist, and L-DOPA on the reserpine-induced muscle rigidity in rats. | 2003 Mar-Apr |
|
| [Effect of catecholamines synthesis blockade on functional status of hypothalamic vasopressinergic neurons in dehydrated rats]. | 2003 May-Jun |
|
| Monoamine depletion in psychiatric and healthy populations: review. | 2003 Nov |
|
| Sensorimotor deficits in a unilateral intrastriatal 6-OHDA partial lesion model of Parkinson's disease in marmoset monkeys. | 2003 Oct |
|
| 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 |
|
| Gliomatosis cerebri evaluated by 18Falpha-methyl tyrosine positron-emission tomography. | 2003 Oct |
|
| 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 |
|
| Potential mechanisms responsible for chlorotriazine-induced alterations in catecholamines in pheochromocytoma (PC12) cells. | 2003 Oct 31 |
|
| Dopamine depletion and in vivo binding of PET D1 receptor radioligands: implications for imaging studies in schizophrenia. | 2003 Sep |
|
| Neurochemical aspects of susceptibility to depression. | 2003 Sep 10 |
|
| Parkin gene inactivation alters behaviour and dopamine neurotransmission in the mouse. | 2003 Sep 15 |
|
| Expression of tyrosine hydroxylase in lymphocytes and effect of endogenous catecholamines on lymphocyte function. | 2004 |
|
| 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 |
|
| Postnatal regulation by monoamines of vasopressin expression in the neuroendocrine hypothalamus of MAO-A-deficient mice. | 2004 Feb |
|
| 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 |
|
| Methamphetamine produces neuronal inclusions in the nigrostriatal system and in PC12 cells. | 2004 Jan |
|
| Differential effects of local versus systemic angiotensin II in the regulation of leptin release from adipocytes. | 2004 Jan |
|
| [Effect of catecholamines on migration and differentiation of gonadotropin releasing hormone-neurons in rats]. | 2004 Jan-Feb |
|
| Carnitine palmitoyltransferase-1 (CPT-1) activity stimulation by cerulenin via sympathetic nervous system activation overrides cerulenin's peripheral effect. | 2004 Jul |
|
| Stress- as well as suckling-induced prolactin release is blocked by a structural analogue of the putative hypophysiotrophic prolactin-releasing factor, salsolinol. | 2004 Mar |
Sample Use Guides
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
| Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 10:20:17 GMT 2023
by
admin
on
Sat Dec 16 10:20:17 GMT 2023
|
| Record UNII |
094DKY9OHM
|
| Record Status |
Validated (UNII)
|
| Record Version |
|
-
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094DKY9OHM
Created by
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22812810
Created by
admin on Sat Dec 16 10:20:17 GMT 2023 , Edited by admin on Sat Dec 16 10:20:17 GMT 2023
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72200-50-1
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admin on Sat Dec 16 10:20:17 GMT 2023 , Edited by admin on Sat Dec 16 10:20:17 GMT 2023
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