Tyrosine hydroxylase enzyme
Metyrosine inhibits tyrosine hydroxylase. [2]

Metyrosine induces sleep by blocking tyrosine kinases, which releases stored catecholamines [2].
Metyrosine is a methylated tyrosine, a catecholamine synthesis antagonist with antihypertensive property. Metyrosine competitively inhibits tyrosine 3-monooxygenase, an enzyme that activates molecular oxygen to catalyze the hydroxylation of tyrosine to dihydroxyphenylalanine (Dopa), an intermediate to catecholamine (dopamine, norepinephrine, and epinephrine) production. This agent reduces the elevated levels of catecholamines associated with pheochromocytoma, thereby preventing hypertension.

Carrageenan modulator is lowered by metyrosine (50–200 mg/kg; ip) [1]. Male albino Wistar rats with carrageenan-induced rat paw edema are the animal model of resistance to the anti-activity of metyrosine (50–200 mg/kg; ip) at dosages of 50, 100, and 200 mg/kg [2].

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Metyrosine is described as a very effective drug for blood pressure control in patients with pheochromocytoma. It acts by inhibiting tyrosine hydroxylase, thereby causing depletion of adrenal stores of catecholamines. [2]
When used in combination with α-blockers preoperatively, Metyrosine results in less labile blood pressure during anesthesia and surgery, reduced intraoperative blood loss, and reduced volume replacement requirements during surgery, compared to the use of α-blockers alone. [2]

Animal/Disease Models: Male albino Wistar rats (carrageenan-induced rat paw edema)[2]
Doses: 50, 100 or 200 mg/kg
Route of Administration: I.p.
Experimental Results: diminished carrageenan inflammation at 50, 100 and 200 mg/kg doses (40%, 67% and 87%, respectively, at 4 h).

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In this study, the anti-inflammatory and anti-ulcerative effects of metyrosine, a selective tyrosine hydroxylase enzyme inhibitor, were investigated in rats. For ulcer experiments, indomethacin-induced gastric ulcer tests and ethanol-induced gastric ulcer tests were used. For these experiments, rats were fasted for 24 h. Different doses of metyrosine and 25 mg/kg doses of ranitidine were administered to rats, followed by indomethacin at 25 mg/kg for the indomethacin-induced ulcer test, or 50% ethanol for the ethanol-induced test. Results have shown that at all of the doses used (50, 100 and 200 mg/kg), metyrosine had significant anti-ulcerative effects in both indomethacin and ethanol-induced ulcer tests. Metyrosine doses of 100 and 200 mg/kg (especially the 200 mg/kg dose) also inhibited carrageenan-induced paw inflammation even more effectively than indomethacin. In addition, to characterize the anti-inflammatory mechanism of metyrosine we investigated its effects on cyclooxygenase (COX) activity in inflammatory tissue (rat paw). The results showed that all doses of metyrosine significantly inhibited high COX-2 activity. The degree of COX-2 inhibition correlated with the increase in anti-inflammatory activity. In conclusion, we found that metyrosine has more anti-inflammatory effects than indomethacin and that these effects can be attributed to the selective inhibition of COX-2 enzymes by metyrosine. We also found that adrenalin levels are reduced upon metyrosine treatment, which may be the cause of the observed gastro-protective effects of this compound.[1]

Absorption, Distribution and Excretion
Easily absorbed from the gastrointestinal tract. As the first and rate-limiting step, blockade of tyrosine hydroxylase activity leads to decreased endogenous catecholamine levels, typically manifested as reduced urinary excretion of catecholamines and their metabolites. Metabolism/Metabolites Very little biotransformation; catechol metabolites account for less than 1% of the administered dose. Biological Half-Life 3.4 to 3.7 hours

Side effects of methyltyrosine include sedation, depression, anxiety, galactorrhea, and rare extrapyramidal side effects. Due to these side effects, methyltyrosine is usually used only for short-term treatment. [2]

[1]. Gastric anti-ulcerative and anti-inflammatory activity of metyrosine in rats. Pharmacol Rep. 2010;62(1):113‐119.

[2]. Medical management of pheochromocytoma: Role of the endocrinologist. Indian J Endocrinol Metab. 2011;15 Suppl 4(Suppl4):S329‐S336.

α-Methyl-L-tyrosine is an L-tyrosine derivative formed by introducing an additional methyl substituent at the 2-position of L-tyrosine. It is a tyrosine 3-monooxygenase inhibitor, thus inhibiting catecholamine synthesis. It is used to control symptoms caused by excessive sympathetic nerve excitation in patients with pheochromocytoma. It has antihypertensive effects and is an EC 1.14.16.2 (tyrosine 3-monooxygenase) inhibitor. It is an L-tyrosine derivative and also a non-protein L-α-amino acid. (Martindale, Pharmacopoeia Supplement, 30th edition)
Methyltyrosine is a catecholamine synthesis inhibitor. The mechanism of action of methyltyrosine is as a catecholamine synthesis inhibitor.
Methyltyrosine is a methylated tyrosine and a catecholamine synthesis antagonist with antihypertensive effects. Methionine competitively inhibits tyrosine 3-monooxygenase, an enzyme that activates molecular oxygen and catalyzes the hydroxylation of tyrosine to dihydroxyphenylalanine (DOPA). DOPA is an intermediate in the synthesis of catecholamines (dopamine, norepinephrine, and epinephrine). This drug can reduce the elevated catecholamine levels associated with pheochromocytoma, thereby preventing hypertension.
Tyrosine 3-monooxygenase inhibitor, therefore inhibiting catecholamine synthesis. This product is used to control symptoms of sympathetic hyperexcitability in patients with pheochromocytoma. (Martindale, Pharmacopoeia Supplement, 30th Edition)
Indications
For the treatment of patients with pheochromocytoma, for preoperative preparation, for the management of patients with contraindications to surgery, and for the long-term treatment of patients with malignant pheochromocytoma.
Mechanism of Action
Methionine inhibits tyrosine hydroxylase, which catalyzes the first step in the biosynthesis of catecholamines, namely the conversion of tyrosine to dihydroxyphenylalanine (DOPA). Since the first step is also the rate-limiting step, blocking tyrosine hydroxylase activity leads to a reduction in endogenous catecholamine levels and their synthesis. This, in turn, lowers the levels of catecholamines (dopamine, epinephrine, and norepinephrine) in the body, typically measured by a decrease in the excretion of catecholamines and their metabolites in urine. A major end result of reduced catecholamines is a decrease in blood pressure.

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Pharmacodynamics
In patients with pheochromocytoma, due to the excess production of norepinephrine and epinephrine in their bodies, daily administration of 1 to 4 grams of methyltyrosine can reduce catecholamine biosynthesis by approximately 35% to 80%, which can be measured by the total excretion of catecholamines and their metabolites (meta-repinephrine and vanillylmandelic acid). The maximum biochemical effect typically occurs within 2 to 3 days, and after discontinuation of methyltyrosine, the concentration of catecholamines and their metabolites in urine typically returns to pre-treatment levels within 3 to 4 days. Most patients with pheochromocytoma treated with methyltyrosine experienced a reduction in the frequency and severity of hypertension, along with relief of accompanying symptoms such as headache, nausea, sweating, and tachycardia. In patients who responded well to methyltyrosine treatment, blood pressure gradually decreased over the first two days; after discontinuation, blood pressure typically returned to pre-treatment levels within two to three days. Methyltyrosine is used as a preoperative medication for pheochromocytoma to control blood pressure. The initial dose is 250 mg three times daily. The dose is then gradually increased until the total daily dose reaches 1.5 to 4 g. [2] In the short term preoperatively, methyltyrosine can be used in combination with alpha-blockers and beta-blockers. [2] Literature indicates that methyltyrosine is currently unavailable in India. [2]
Some literature suggests that preoperative blood pressure control may not change surgical outcomes and intraoperative complications, but the authors of this paper believe that adequate preoperative blood pressure control should be achieved. [2]

C10H13NO3

195.2151

195.09

672-87-7

Metyrosine-13C9,15N,d7;1994331-23-5

441350

White to off-white solid powder

1.283g/cm3

383.7ºC at 760 mmHg

320-340°C dec.

185.9ºC

1.599

1.437

3

4

3

14

211

1

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

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

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

Demser; Metirosine; Racemetirosine; METYROSINE; 672-87-7; alpha-Methyl-L-tyrosine; Metirosine; Demser; Methyltyrosine; (S)-alpha-Methyltyrosine; (S)-2-Amino-3-(4-hydroxyphenyl)-2-methylpropanoic acid; α-Methyltyrosine

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ~5 mg/mL (~25.61 mM)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)