Methyldopa Chemical Properties
- Melting point:
- ≥300 °C
- Boiling point:
- 350.89°C (rough estimate)
- 1.2545 (rough estimate)
- refractive index
- -14 ° (C=1, H2O)
- storage temp.
- Store at RT
- Water Solubility
- 10g/L(temperature not stated)
- CAS DataBase Reference
- 555-30-6(CAS DataBase Reference)
- EPA Substance Registry System
- Methyldopa (555-30-6)
- Language:EnglishProvider:2-Amino-3-(3,4-dihydroxyphenyl)-2-methyl-propanoic acid
Methyldopa Usage And Synthesis
Antihypertensor;L-aromatic aminoacid decarboxylase inhibitor
vitamin, coenzyme B12
ChEBI: A derivative of L-tyrosine having a methyl group at the alpha-position and an additional hydroxy group at the 3-position on the phenyl ring.
The spectrum of activity of α-methyldopa (Aldomet) lies between those of the more potent agents, such as guanethidine, and the milder antihypertensives, such as reserpine. α-Methyldopa is a structural analogue of dihydroxyphenylalanine (dopa) and differs from dopa only by the presence of a methyl group on the -carbon of the side chain.
Methyldopa differs structurally from L-DOPA only in the presence of a -methyl group. Originally synthesized as an AADC inhibitor,methyldopa ultimately decreases the concentration of DA,NE, E, and serotonin in the CNS and periphery. However,its mechanism of action is not caused by its inhibition ofAADC but, rather, by its metabolism in the CNS to its activemetabolite ( β-methylnorepinephrine). Methyldopa istransported actively into CNS via an aromatic amino acidtransporter, where it is decarboxylated by AADC in thebrain to (1R,2S)- α-methyldopamine. This intermediate, inturn, is stereospecifically β-hydroxylated by DBH to givethe (1R,2S)-α-methylnorepinephrine. This active metaboliteis a selective α2-agonist because it has correct(1R,2S) configuration . It is currently postulated that α-methylnorepinephrine acts on α2-receptors in theCNS in the same manner as clonidine, to decrease sympatheticoutflow and lower blood pressure.
Colorless or almost colorless crystals or white to yellowish-white fine powder. Almost tasteless. In the sesquihydrate form. pH (saturated aqueous solution) about 5.0.
Air & Water Reactions
Very hygroscopic. Slightly water soluble. May be sensitive to prolonged exposure to air and light. The stability of aqueous solutions is markedly dependent on pH, oxygen and the amount of initial reactant. Aqueous solutions are stable for up to 50 hours in acid and neutral pH (6.2). At pH 8.0, decomposition products are formed in 3 to 5 hours. Solutions develop a red tint that becomes progressively darker (eventually forming a black precipitate).
Methyldopa undergoes catalytic oxygenation in the presence of magnesium, cupric, cobalt, nickel and ferric ions . A weakly acidic amino acid.
Flash point data for Methyldopa are not available; however, Methyldopa is probably combustible.
L-aromatic amino acid decarboxylase inhibitor. Antihypertensive.
Mechanism of action
A number of theories have been put forward to account for the hypotensive action of α-methyldopa. Current evidence suggests that for α-methyldopa to be an antihypertensive agent, it must be converted to α-methylnorepinephrine; however, its site of action appears to be in the brain rather than in the periphery. Systemically administered α-methyldopa rapidly enters the brain, where it accumulates in noradrenergic nerves, is converted to α-methylnorepinephrine, and is released. Released α-methylnorepinephrine activates CNS α- adrenoceptors whose function is to decrease sympathetic outflow. Why α-methylnorepinephrine decreases sympathetic outflow more effectively than does the naturally occurring transmitter is not entirely clear.
The primary hemodynamic alteration responsible for
the hypotensive effects of α-methyldopa remains in dispute.
When the patient is supine, the reduction in blood
pressure produced by α-methyldopa correlates best
with a decrease in peripheral vascular resistance, cardiac
output being only slightly reduced. When the patient
is upright, the fall in blood pressure corresponds
more closely with a reduced cardiac output.
An important aspect of α-methyldopa’s hemodynamic effects is that renal blood flow and glomerular filtration rate are not reduced. As occurs with most sympathetic depressant drugs and vasodilators, long-term therapy with α-methyldopa leads to fluid retention, edema formation, and plasma volume expansion.While data conflict somewhat, it is generally thought that - methyldopa suppresses plasma renin activity.
α-Methyldopa is not generally believed to be suitable
for monotherapy of primary hypertension. Because
plasma volume increases as the duration of α-methyldopa
therapy is extended, the drug should be used in
conjunction with a diuretic; this will produce a significantly
greater fall in blood pressure than would occur
with either drug used alone. Because α-methyldopa lowers
blood pressure without compromising either renal
blood flow or the glomerular filtration rate, it is particularly
valuable in hypertension complicated by renal disease.
However, if end-stage renal failure accompanies severe
hypertension,α-methyldopa may not be effective.
The presence of α-methyldopa and its metabolites in the urine reduces the diagnostic value of urinary catecholamine measurements as an indicator of pheochromocytoma, since these substances interfere with the fluorescence assay for catecholamines.
The most commonly encountered side effects of α-
methyldopa are sedation and drowsiness.These CNS effects
are probably the result of reductions in brain catecholamine
levels. Other side effects, also typical of
sympathetic depression, are dry mouth, nasal congestion,
orthostatic hypertension, and impotence.
Autoimmune reactions associated with α-methyldopa treatment include thrombocytopenia and leukopenia. Since a few cases of an α-methyldopa–induced hepatitis have occurred, the drug is contraindicated in patients with active hepatic disease. Flulike symptoms also are known to occur.
Poison by intraperitoneal route. Moderately toxic by ingestion and intravenous routes. Human systemic effects by ingestion: fasciculations, hallucinations, distorted perceptions, tremors, allergic dermatitis, necrotic gastrointestinal changes. An experimental teratogen. Human reproductive effects: menstrual cycle changes or disorders, effects on newborn including abnormal neonatal measures and growth statistics, biochemical and metabolic changes. Experimental reproductive effects. Mutation data reported. When heated to decomposition it emits toxic fumes of NOx
Approximately 50% of an orally administered dose of α-methyldopa is absorbed from the gastrointestinal tract. Both peak plasma drug levels and maximal blood pressure–lowering effects are observed 2 to 6 hours after oral administration. A considerable amount of unchanged α-methyldopa and several conjugated and decarboxylated metabolites can be found in the urine.
Recrystallise methyldopa from H2O. [Reinhold et al. J Org Chem 33 1209 1968.] The L-isomer forms a sesquihydrate from H2O m 302-304o (dec), and the anhydrous crystals are hygroscopic, 23D -4.0o (c 1, 0.1N HCl), 546 +154.5o (c 5, CuSO4 solution). It has max at 281nm ( 2780). Its solubility in H2O at 25o is ~10mg/mL and the pH of an aqueous solution is ~5.0. It is insoluble in most organic solvents. [Stein et al. J Am Chem Soc 77 700 1955, Beilstein 4 IV 2505.]
- Hydantoic acid
- LABOTEST-BB LT00847269
- Dimethyl methyldopa
- (-)-3-(3,4-DIHYDROXYPHENYL)-2-METHYL-L-ALANINE SESQUIHYDRATE,3-(3,4-DIHYDROXYPHENYL)-2-METHYL-L-ALANINE SESQUIHYDRATE,L-(-)-ALPHA-METHYLDOPA ((-)-3-(3,4-DIHYDROXYPHENYL)-2-METHYL-L-ALANINE SESQUIHYDRATE),3-(3,4-Dihydroxyphenyl)-2-methyl-L-alanine, Methyl-L-DOPA, MK-351
- METHYL THIOPHENE-2-CARBOXYLATE
- Tris Base
- Methyl acrylate
- Bensulfuron methyl
- 3-(4-Hydroxyphenyl)propionic acid
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