What Is Methyldopa?

Methyldopa is an antihypertensive drug. It is a white or off-white crystalline powder; it is odorless. It is mainly converted to methyl norepinephrine in the center. Methyl norepinephrine is a strong central alpha receptor agonist. It is used for moderate, severe or malignant hypertension, as well as sedation and reducing intraocular pressure. It is especially suitable for renal hypertension and hypertension with impaired renal function. This medicine mainly damages the cardiovascular system, liver and blood system.

Chinese name: Methyldopa
Foreign name: alpha-methyldopa

Molecular formula: C10H13NO4
Molecular weight: 211.2145
CAS: 555-30-6

Methyldopa Basic Information

Chinese name: methyldopa

Chinese alias: 2-amino-3- (3,4-dihydroxyphenyl) -2-methyl-propionic acid; L-methyldopa; 3- (3,4-dihydroxyphenyl) -2- Methyl-L-alanine;

English name: L-(-)--Methyldopa

English alias: Methyldopa Sesquihydrate; alpha-methyl-L-dopa; L-Tyrosine, 3-hydroxy--methyl-; Methyldopa; -methyl-L-dopa;

CAS number: 555-30-6

Molecular formula: C ₁₀ H ₁₃ NO4

Molecular weight: 211.21500

Exact mass: 211.08400

PSA: 103.78000

LogP: 1.14260

Methyldopa physicochemical properties

Appearance and properties: colorless or almost colorless crystal or white to light yellow-white fine powder, almost tasteless in the form of hydrate

Density: 1.403g / cm ³

Melting point: 300 ° C

Boiling point: 441.6ºC at 760mmHg

Flash point: 220.9ºC

Refractive index: -14 ° (C = 1, H2O)

Water solubility: soluble in water

Solubility: DMSO (75 mM), dilute hydrochloric acid

Stability: Stable under normal temperatures and pressures.

Storage conditions: Keep container closed when not in use. Store in a cool, dry, well-ventilated area away from incompatible substances. ^[1]

Methyldopa production method

The vanillin was methylated with dimethyl sulfate to verataldehyde, and then condensed with nitroethane to obtain 1- (2-nitropropenyl) -3 ', 4'-dimethoxybenzene. The powder is reduced and hydrolyzed to produce 3 ', 4'-dimethoxyphenylacetone (see 14945), and then cyclized, ring-opened, and hydrolyzed to obtain DL-methyldopa. Quitoba. ^[1]

Methyldopa drug analysis

Methyl dopa identification

(1) Take this product, add 0.1mol / L hydrochloric acid solution to dissolve and dilute it to make a solution containing about 0.04mg per 1ml. As measured by ultraviolet-visible spectrophotometry (General Rule 0401), it has a maximum absorption at a wavelength of 280nm , Its absorbance is about 0.48.

(2) Take 10mg of this product, add 3 drops of ninhydrin test solution, and show dark purple after leaving.

Methyldopa examination

For acidity, take 10 g of this product, add 100 ml of freshly boiled cold water to dissolve, add 1 drop of methyl red indicator liquid, if it is red, add 0.5 ml of sodium hydroxide titration solution (0.1mol / L), it should be yellow.

Take 0.25g of hydride and check it according to law (General Rule 0801). Compared with the control solution made of 7.0ml of standard sodium gas solution, it must not be deeper (0.028%).

Take the appropriate amount of this substance, add the mobile phase to dissolve and quantitatively dilute it to make a solution containing about 1mg per 1ml as the test solution; take a precise amount and use the mobile phase to quantitatively dilute to make a solution containing 5pg per 1m. , As a control solution. Measured according to effective liquid chromatography (General Rule 0512), using octadecylsilane bonded silica as a filler; acetonitrile-phosphate buffer solution (take 2 g of potassium dihydrogen phosphate and lg of phosphate, and add 900 ml of water to dissolve) : 95) is a mobile phase; the detection wavelength is 278 nm. The number of theoretical plates is calculated to be not less than 2000 based on the methyl dopa peak. Precisely measure 20 µl each of the test solution and the control solution, and inject them into the liquid chromatograph respectively, and record the chromatogram to 8 times the peak retention time of the main component. If there is an impurity peak in the chromatogram of the test solution, the area of a single impurity peak must not be larger than the area of the main peak of the control solution (0.5%), and the sum of the area of each impurity peak must not be more than 2 times (1.0%) the area of the main peak of the control solution.

Loss on drying: Take this product and dry it at 125 to constant weight. The weight loss should be 10.0% ~ 13.0% (General rule 0831).

Take 10 g of this product and check it according to law (General Rule 0841). The remaining residue should not exceed 0.1%.

The heavy metal shall be taken as the residue left under the burning residue, and shall be inspected according to law (General Law 0821, Second Law), and the heavy metal shall not exceed 10 parts per million.

Determination of methyldopa

Take about 0.15g of this product, accurately weigh, add 20ml of glacial acetic acid to dissolve, add 1 drop of crystal violet indicator solution, titrate with high gas acid titration solution (0.1mol / U until the solution is blue-green, and use the titration result with Blank test correction. Each 1ml of perchloric acid titration solution (0.1mol / L) is equivalent to 21.12mg of C ₁₀ H ₁₃ N0 _4. ^[2]

Methyldopa related drug label information

Methyldopa drug name

Methyldopa

Methyldopa English name

Methyldopa

Methyldopa alias

Adolmet; Methyldopa; -Methyldopa; Aldomet; Domesin; Medopa

Methyl dopa classification

Circulatory Drugs> Antihypertensive Drugs> Adrenergic Neuronal Blockers

Methyldopa dosage form

1.0.25g;

2. Tablet: 0.25g, 0.5g.

Pharmacological effects of methyldopa

Methyldopa is mainly converted to methyl norepinephrine in the center. Methyl norepinephrine is a strong central alpha receptor agonist that excites inhibitory neurons between the medulla medulla nucleus and the vascular motility center, inhibits the peripheral sympathetic nerves, thereby inhibiting the heart and kidneys. The sympathetic impulse with the surrounding blood vessels is transmitted, at the same time, the resistance of the surrounding blood vessels and the plasma renin and renin activity are reduced, and the blood pressure is thus reduced.

Methyldopa pharmacokinetics

A single oral dose is 4-6 hours, and multiple oral doses are 2-3 days. The plasma concentration reached a peak in 2 to 4 hours. The duration of single administration is 12-24 hours. Multiple administration is 24 to 48 hours. The concentration in the body is highest in the kidney, followed by heart and lung. The protein binding rate is less than 20%. The metabolic site is in the liver, and the metabolite is alpha methyl norepinephrine. Excreted by the kidney, 90% of methyldopa and its metabolites are excreted with urine.

Methyldopa indication

Hypertension is more suitable for renal hypertension and pregnancy hypertension.

Methyldopa contraindications

Acute liver disease and pheochromocytoma are contraindicated.

Methyldopa considerations

1. Patients with a history of coronary heart disease, tremor, paralysis, or depression should be used with caution.

2. Methyldopa can cause fluorescence and interfere with certain assays. There are also reports of positive platelet and leukocyte antibody complement binding tests, positive Coombs tests, and positive antinuclear antibodies, which can be recovered after drug withdrawal.

3. During the treatment, blood routine and liver function should be monitored. Blood urea nitrogen, potassium, potassium, and uric acid may be increased. Blood transaminase and bilirubin may increase, suggesting liver damage.

Methyldopa adverse reactions

Drowsiness, fatigue, depression, dizziness, headache, dry mouth, orthostatic hypotension. There are also diarrhea, fever, edema, pancreatitis, rash, salivary gland inflammation, and sexual dysfunction. Occasionally Parkinson's syndrome, arthralgia and myalgia, exacerbation of angina pectoris, bradycardia, leukopenia, thrombocytopenia, and jaundice.

Methyldopa dosage

1. (1) Adults: 0.25g each time, 2 to 3 times a day, can be increased every 2 days, the maintenance dose is 0.5 to 2g per day, and the maximum dose should not exceed 3g per day. (2) Children: 10mg / kg per day, can be increased to 65mg / kg every 2 days, the maximum dose should not exceed 3g per day.

2. Intravenous injection: (1) Adults: 0.25 to 1 g each time, 3 to 4 times a day, the maximum dose should not exceed 3 g per day. (2) Children: 5 to 10 mg / kg each time, 3 to 4 times per day, which can be increased to 65 mg / kg or 3 g per day.

Interaction of methyldopa with methyldopa

Synergistic effect with other antihypertensive drugs, but not with reserpine, monoamine oxidase inhibitors, -blockers. Can enhance the toxicity of lithium salts, monoamine oxidase inhibitors, and sympathomimetic drugs. Can enhance the effect of levodopa, oral anticoagulants. Tricyclic antidepressants and non-steroidal anti-inflammatory analgesics can attenuate the hypotensive effect of methyldopa. The combination of diuretics and other antihypertensive drugs with methyldopa can enhance the antihypertensive effect. Therefore, when used with other antihypertensive drugs, the starting dose of methyldopa should be small. It can increase blood lactogen concentration and interfere with the action of bromocriptine. Methyldopa can prolong the central effects of barbiturates and halothanes. Patients with methyldopa experienced an increase in blood pressure when propranolol was administered intravenously.

Methyldopa Expert Reviews

Methylpolymethyldopa is a medium-to-strong antihypertensive drug, used for the treatment of moderate and severe hypertension, and can be used for several years. Applicable to renal hypertension and pregnancy hypertension, with significant curative effect. The drug can be used alone or in combination with a diuretic or beta blocker.

Methyldopa methyldopa poisoning

Methyldopa (Metadopa, Admiralty) is a central antihypertensive drug used for moderate, severe or malignant hypertension, as well as sedative and reducing intraocular pressure. It is especially suitable for renal hypertension and hypertension with impaired renal function. The drug is not completely absorbed orally, and it takes effect 4 to 6 hours after taking it. The blood concentration reaches a peak at 6 to 8 hours, and the half-life is 7 to 16 hours. About two-thirds are excreted by the kidney, and those with poor renal function have a certain accumulation.

The initial oral dose is 0.25 g each time, 2 to 3 / d, and the dose is adjusted according to the condition, and the maintenance amount is 0.5 to 2 g / d, divided into 2 to 4 times, and the extreme amount is 3 g / d. Pediatric 3 ~ 5mg / kg, 2 ~ 3 / d, the initial dose should start with a small dose and gradually increase. The concentration of human poisoning blood drug was 1.0%, LD50 mice were 5.3 to 15.0 g / kg by mouth, and 1.96 g / kg by vein. This medicine mainly damages the cardiovascular system, liver and blood system.

Clinical manifestations of methyldopa poisoning

Adverse reaction

Such as dizziness, dizziness, drowsiness, headache, fatigue, lack of concentration; dry mouth, nausea, vomiting, constipation, abdominal distension, black tongue or ulcers; orthostatic hypotension, bradycardia, edema.

2. Poisoning performance

(1) Hypotension and syncope.

(2) Myocarditis, severe bradycardia, and atrioventricular block.

(3) Liver damage can cause fatigue, anorexia, and elevated serum aminotransferases. Acute severe hepatitis can be seen in severe cases.

(4) Hemolytic anemia, granulocytopenia, thrombocytopenia, etc. are caused by azomethopa.

Treatment of methyldopa poisoning

The main points of treatment for methyldopa poisoning are:

1. Discontinue the drug immediately.

2. Stomach lavage, vomiting, catharsis, and large infusion at the same time, accelerate the excretion of drugs in the body.

3. Hypotension, shock, booster medication, correct shock.

4. Bradycardia, intravenous isoprenaline can be used.

5. Liver damage should be treated with liver protection, such as Ganlixin and tiopronin. ^[3-4]