3-Hydroxy-L-tyrosin Chemische Eigenschaften,Einsatz,Produktion Methoden
R-Sätze Betriebsanweisung:
R22:Gesundheitsschädlich beim Verschlucken.
R36/37/38:Reizt die Augen, die Atmungsorgane und die Haut.
R20/21/22:Gesundheitsschädlich beim Einatmen,Verschlucken und Berührung mit der Haut.
S-Sätze Betriebsanweisung:
S26:Bei Berührung mit den Augen sofort gründlich mit Wasser abspülen und Arzt konsultieren.
S36:DE: Bei der Arbeit geeignete Schutzkleidung tragen.
S24/25:Berührung mit den Augen und der Haut vermeiden.
Beschreibung
Levodopa is an amino acid precursor of dopamine with antiparkinsonian properties. Levodopa is a prodrug that is converted to dopamine by DOPA decarboxylase and can cross the blood-brain barrier. When in the brain, levodopa is decarboxylated to dopamine and stimulates the dopaminergic receptors, thereby compensating for the depleted supply of endogenous dopamine seen in Parkinson's disease. To assure that adequate concentrations of levodopa reach the central nervous system, it is administered with carbidopa, a decarboxylase inhibitor that does not cross the blood-brain barrier, thereby diminishing the decarboxylation and inactivation of levodopa in peripheral tissues and increasing the delivery of dopamine to the CNS.
Chemische Eigenschaften
L-Dopa [59-92-7], levodopa, crystallizes as colorless, odorless, and tasteless needles from water, mp 276-278℃(decomp.). It is freely soluble in dilute hydrochloric and formic acids but practically insoluble in ethanol, benzene, chloroform, and ethyl acetate. Solubility in water is 66 mg/40 mL. In the presence of moisture, l-dopa is rapidly oxidized by atmospheric oxygen, with darkening.
Verwenden
Levodopa is an immediate precursor of dopamine and product of tyrosine hydroxylase. It derived from vanillin is widely used for treatment of Parkinson’s disease, most often in combination with peripheral decarboxylase inhibitors such as benserazide and carbidopa.
Definition
ChEBI: Levodopa is an optically active form of dopa having L-configuration. Used to treat the stiffness, tremors, spasms, and poor muscle control of Parkinson's disease.
Biologische Funktion
Levodopa (L-DOPA), the most reliable and effective drug used in the treatment of parkinsonism, can be considered a form of replacement therapy. Levodopa is the biochemical precursor of dopamine. It is used to elevate dopamine levels in the neostriatum of parkinsonian patients. Dopamine itself does not cross the blood-brain barrier and therefore has no CNS effects. However, levodopa, as an amino acid, is transported into the brain by amino acid transport systems, where it is converted to dopamine by the enzyme L-aromatic amino acid decarboxylase.
If levodopa is administered alone, it is extensively metabolized by L-aromatic amino acid decarboxylase in the liver, kidney, and gastrointestinal tract. To prevent this peripheral metabolism, levodopa is coadministered with carbidopa (Sinemet), a peripheral decarboxylase inhibitor. The combination of levodopa with carbidopa lowers the necessary dose of levodopa and reduces peripheral side effects associated with its administration.
Allgemeine Beschreibung
Levodopa belongs to a group of the most effective drugs for treating the type of Parkinsonism not caused by medicinal agents. The first significant breakthrough in the treatment of PDcame about with the introduction of high-dose levodopa. Fahn referred to this as a revolutionary development intreating parkinsonian patients. The rationale for the use oflevodopa for the treatment of PD was established in theearly 1960s. Parkinsonian patients were shown to have decreasedstriatal levels of DA and reduced urinary excretionof DA. Since then, levodopa has shown to be remarkablyeffective for treating the symptoms of PD.
Nebenwirkungen
Get medical help immediately if you have any symptoms: fever, unusual muscle stiffness, severe confusion, sweating, fast/irregular heartbeat, and rapid breathing. A severe allergic reaction to this drug is rare. This medication may cause saliva, urine, or sweat to turn dark. This effect is harmless.
Sicherheitsprofil
Poison by ingestion.
Moderately toxic by intravenous and
intraperitoneal routes. Human systemic
effects by ingestion: somnolence,
hallucinations and distorted perceptions,
toxic psychosis, motor activity changes,
ataxia, dyspnea. Experimental teratogenic
and reproductive effects. Questionable
human carcinogen producing skin tumors.
Human mutation data reported. An
anticholinergic agent used as an anti Parhnsonian drug. When heated to
decomposition it emits toxic fumes of NOx
läuterung methode
Likely impurities are vanillin, hippuric acid, 3-methoxytyrosine and 3-aminotyrosine. DOPA recrystallises from large volumes of H2O forming colourless white needles; its solubility in H2O is 0.165%, but it is insoluble in EtOH, *C6H6, CHCl3, and EtOAc. Also crystallise it by dissolving it in dilute HCl and adding dilute ammonia to give pH 5, under N2. Alternatively, crystallise it from dilute aqueous EtOH. It is rapidly oxidised in air when moist, and darkens, particularly in alkaline solution. Dry it in vacuo at 70o in the dark, and store it in a dark container preferably under N2. It has at 220.5nm (log 3.79) and 280nm (log 3.42) in 0.001N max HCl. [Yamada et al. Chem Pharm Bull Jpn 10 693 1962, Bretschneider et al. Helv Chim Acta 56 2857 1973, NMR: Jardetzky & Jardetzky J Biol Chem 233 383 1958, Beilstein 4 IV 2492, 2493.]
3-Hydroxy-L-tyrosin Upstream-Materialien And Downstream Produkte
Upstream-Materialien
Downstream Produkte
(S)-(-)-6,7-DIMETHOXY-1,2,3,4-TETRAHYDROISOQUINOLINE-3-CARBOXYLIC ACID HYDROCHLORIDE
N-(tert-buloxycarbonyl)-3,4-dihydroxy-L-phenylalanine
(S)-Methyl 2-((tert-butoxycarbonyl)aMino)-3-(3,4-dihydroxyphenyl)propanoate
5,6-dihydroxy-1H-indole-2-carboxylic acid
Tetrahydropapaveroline
FMOC-DOPA(ACETONIDE)-OH
L-3,4-DIHYDROXYPHENYLALANINE METHYL ESTER HYDROCHLORIDE
(2S)-5,6-dihydroxy-2,3-dihydro-1H-indole-2-carboxylic acid
