レボドパ 化学特性,用途語,生産方法
外観
白色〜わずかにうすい褐色, 結晶性粉末〜粉末
溶解性
希塩酸に溶けやすい。希アルカリに溶けるが、着色する。水に溶けにくく、エタノール及びアセトンにほとんど溶けない。
解説
L-3-(3,4-ジヒドロキシフェニル)アラニン，ジヒドロキシフェニルアラニン略号DOPA．L-ドーパともいう．ソラマメVicia fava L.の果皮や芽，またヒトの尿，副腎などに存在するが，加水分解中に分解するのでタンパク質中には見いだされていない．L-チロシンをニトロ化，還元，ついでジアゾ化，加水分解して合成できる．針状晶．分解点285 ℃．[α]D－14.28°(1 mol L－1 塩酸)．水に比較的難溶，有機溶媒にほとんど不溶．空気中で容易に酸化され黒化するので，再結晶は亜硫酸を含む水から行う．生体内では酵素によるチロシンの酸化により生成するが，メラニン，アドレナリン，コデイン，モルヒネなどの生体内中間体として重要である．パーキンソン病の治療薬に用いられる．LD50 4898 mg/kg(マウス，経口)．
用途
ドパミンの前駆物質です。
用途
薬理・生理研究用。
用途
その本来の生物学的に必須な役割以外に、レボドパは血液脳関門を通過できる性質を活用して、パーキンソン病（PD）とドパミン反応性デストニア（DSD）の臨床療法に用いられる。医薬品としては、国際一般名を用いてレボドパと呼ばれるのが普通である。これを含む商品名としては、シネメット、パーコーパ、アタメット、スタレボ、マドパー、プロローパ等がある。 補助食品（サプリメント）または向精神薬として用いられる。
効能
パーキンソン病治療薬
商品名
ドパストン (大原薬品工業); ドパストン (大原薬品工業); ドパゾール (アルフレッサファーマ)
説明
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.
化学的特性
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.
使用
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.
定義
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.
生物学の機能
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.
一般的な説明
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.
副作用
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.
安全性プロファイル
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
純化方法
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.]
レボドパ 上流と下流の製品情報
原材料
準備製品
(S)-(-)-6,7-DIMETHOXY-1,2,3,4-TETRAHYDROISOQUINOLINE-3-CARBOXYLIC ACID HYDROCHLORIDE
BOC-3,4-ジヒドロキシ-L-フェニルアラニン
2-((TERT-ブチルトキシカルボニル)アミノ)-3-(3,4-ジヒドロキシフェニル)プロパン酸(S)-メチル
5,6-ジヒドロキシ-1H-インドール-2-カルボン酸
1-(3,4-ジヒドロキシベンジル)-1,2,3,4-テトラヒドロイソキノリン-6,7-ジオール
FMOC-DOPA (アセトニド)-OH
L-DOPAメチルエステル塩酸塩
(S)-2,3-ジヒドロ-5,6-ジヒドロキシ-1H-インドール-2-カルボン酸