methyldopa

メチルドパ 　

WordNet

1. antihypertensive drug (trade name Aldomet) used in the treatment of high blood pressure (同)alpha methyl dopa, Aldomet

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/12/11 09:00:04」(JST)

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Methyldopa

Systematic (IUPAC) name
(S)-2-amino-3-(3,4-dihydroxyphenyl)-2-methyl-propanoic acid
Clinical data
AHFS/Drugs.com	monograph
MedlinePlus	a682242
Pregnancy category	AU: A US: B (No risk in non-human studies)
Legal status	AU: S4 (Prescription only) CA: ℞-only UK: POM (Prescription only) US: ℞-only
Routes of administration	Oral, IV
Pharmacokinetic data
Bioavailability	approximately 50%
Metabolism	Hepatic
Biological half-life	105 minutes
Excretion	Renal for metabolites
Identifiers
CAS Number	555-30-6 Y
ATC code	C02AB01 C02AB02 (racemic)
PubChem	CID: 38853
IUPHAR/BPS	5217
DrugBank	DB00968 Y
ChemSpider	35562 N
UNII	56LH93261Y Y
ChEMBL	CHEMBL459 N
Chemical data
Formula	C10H13NO4
Molecular mass	211.215 g/mol
SMILES C[C@](CC1=CC(=C(C=C1)O)O)(C(=O)O)N
InChI InChI=1S/C10H13NO4/c1-10(11,9(14)15)5-6-2-3-7(12)8(13)4-6/h2-4,12-13H,5,11H2,1H3,(H,14,15)/t10-/m0/s1 N Key:CJCSPKMFHVPWAR-JTQLQIEISA-N N
N (what is this?)  (verify)

Methyldopa (L-α-Methyl-3,4-dihydroxyphenylalanine; Aldomet, Aldoril, Dopamet, Dopegyt, etc.) is an indirect-acting alpha-adrenergic antagonist (being a selective agonist for α₂-adrenergic receptors) psychoactive drug used as a sympatholytic or antihypertensive. Its use is now mostly deprecated following the introduction of alternative safer classes of agents. However, it continues to have a role in otherwise difficult to treat hypertension and gestational hypertension (previously known as pregnancy-induced hypertension (PIH)).

It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.

Medical uses

Methyldopa is used in the clinical treatment of the following disorders:

• Hypertension (or high blood pressure)
• Gestational hypertension (or pregnancy-induced hypertension) and pre-eclampsia

Side effects

Methyldopa is capable of inducing a number of adverse side effects, which range from mild to severe. Nevertheless, they are generally mild when the dose is less than 1 gram per day. Side effects may include:

• Psychological
  • Depression and/or even suicidal ideation, as well as nightmares
  • Apathy and/or anhedonia, as well as dysphoria
  • Anxiety, especially of the social anxiety variant
  • Decreased alertness, awareness, and wakefulness
  • Impaired attention, focus, and concentration
  • Decreased desire, drive, and motivation
  • Fatigue or lethargy and/or malaise or lassitude
  • Sedation or drowsiness and/or somnolence or sleepiness
  • Agitation or restlessness
  • Cognitive and memory impairment
  • Derealization and/or depersonalization, as well as mild psychosis
  • Sexual dysfunction including impaired libido, desire, and drive

• Physiological
  • Dizziness, lightheadedness, or vertigo
  • Miosis or pupil constriction
  • Xerostomia or dry mouth
  • Gastrointestinal disturbances such as diarrhea and/or constipation
  • Headache or migraine
  • Myalgia or muscle aches, arthralgia or joint pain, and/or paresthesia ("pins and needles")
  • Restless legs syndrome (RLS)
  • Parkinsonian symptoms such as muscle tremors, rigidity, hypokinesia, and/or balance or postural instability
  • Akathisia, ataxia, dyskinesia as well as even tardive dyskinesia, and/or dystonia
  • Bell's palsy or facial paralysis
  • Sexual dysfunction consisting of impaired erectile dysfunction and/or anorgasmia
  • Hyperprolactinemia or excess prolactin, gynecomastia/breast enlargement in males, and/or amenorrhoea or absence of menstrual cycles in females
  • Bradycardia or decreased heart rate
  • Hypotension or decreased blood pressure (though this may also be considered a therapeutic benefit)
  • Orthostatic hypotension (also known as postural hypotension)
  • Hepatitis, hepatotoxicity, or liver dysfunction or damage
  • Pancreatitis or inflammation of the pancreas
  • Haemolytic anaemia or deficiency in red blood cells (RBCs)
  • Myelotoxicity or bone marrow suppression, potentially leading to thrombocytopenia or blood platelet deficiency and/or leukopenia or white blood cell (WBC) deficiency
  • Hypersensitivity such as lupus erythematosus, myocarditis, and/or pericarditis
  • Lichenoid reactions such as skin lesions and/or rashes
  • Pallor

Rebound/withdrawal

Rebound hypertension via withdrawal on account of tolerance upon the abrupt discontinuation of methyldopa has been reported.

See also

• Difluoromethyldopa
• D-DOPA (Dextrodopa)
• L-DOPA (Levodopa; Sinemet, Parcopa, Atamet, Stalevo, Madopar, Prolopa, etc.)
• L-DOPS (Droxidopa)
• Dopamine (Intropan, Inovan, Revivan, Rivimine, Dopastat, Dynatra, etc.)
• Norepinephrine (Noradrenaline; Levophed, etc.)
• Epinephrine (Adrenaline; Adrenalin, EpiPed, Twinject, etc.)

Mechanism of Action

Methyldopa has a dual mechanism of action:

• It is a competitive inhibitor of the enzyme DOPA decarboxylase, also known as aromatic L-amino acid decarboxylase, which converts L-DOPA into dopamine. Dopamine is a precursor for norepinephrine (noradrenaline) and subsequently epinephrine (adrenaline). This inhibition results in reduced dopaminergic and adrenergic neurotransmission in the peripheral nervous system. This effect may lower blood pressure and cause central nervous system effects such as depression, anxiety, apathy, anhedonia, and parkinsonism. In addition, decreased dopamine may reduce its inhibitory effect on prolactin leading to signs and symptoms of hyperprolactinemia.

• It is converted to α-methylnorepinephrine by dopamine beta-hydroxylase (DBH). α-methylnorepinephrine is an agonist of presynaptic central nervous system α₂-adrenergic receptors. Activation of these receptors in the brainstem appears to inhibit sympathetic nervous system output and lower blood pressure. This is also the mechanism of action of clonidine.

Pharmacokinetics

Methyldopa exhibits variable absorption from the gastrointestinal tract. It is metabolized in the liver and intestines and is excreted in urine.

History

When methyldopa was first introduced, it was the mainstay of antihypertensive treatment, but its use has declined on account of relatively severe adverse side effects, with increased use of other safer and more tolerable agents such as alpha blockers, beta blockers, and calcium channel blockers. Nonetheless, one of methyldopa's still current indications is in the management of pregnancy-induced hypertension (PIH), as it is relatively safe in pregnancy compared to many other antihypertensives which may affect the fetus.

References

UpToDate Contents

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• 1. 妊婦および出産後女性における高血圧のマネージメント management of hypertension in pregnant and postpartum women
• 2. 高血圧の周術期マネージメント perioperative management of hypertension
• 3. 薬物誘発性ループス drug induced lupus
• 4. 降圧剤と脂質 antihypertensive drugs and lipids
• 5. 後腹膜線維症の臨床症状および診断 clinical manifestations and diagnosis of retroperitoneal fibrosis

English Journal

• An Eco-Friendly Direct Injection HPLC Method for Methyldopa Determination in Serum by Mixed-Mode Chromatography Using a Single Protein-Coated Column.

• Emara S1, Masujima T2, Zarad W3, Kamal M4, Fouad M5, El-Bagary R5.
• Journal of chromatographic science.J Chromatogr Sci.2015 Sep;53(8):1353-60. doi: 10.1093/chromsci/bmv024. Epub 2015 Apr 1.
• A simple, rapid and environment-friendly direct injection HPLC method for the determination of methyldopa (MTD) in human serum has been developed and validated. The method was based on cleanup and separation of MTD from serum by mixed-mode liquid chromatography using a single protein-coated TSK gel
• PMID 25834172

• Salvianolic acid B as a substrate and weak catechol-O-methyltransferase inhibitor in rats.

• Qi Q1, Cao L, Li F, Wang H, Liu H, Hao H, Hao K.
• Xenobiotica; the fate of foreign compounds in biological systems.Xenobiotica.2015 Sep;45(9):820-7. doi: 10.3109/00498254.2015.1017753. Epub 2015 Jun 12.
• 1. The aim of this study was to investigate the biotransformation of salvianolic acid B (SAB) by catechol-O-methyltransferase (COMT) and its interaction with levodopa (l-DOPA) methylation in rats. 2. The enzyme kinetics of SAB were studied after incubation with rat COMT. The in vivo SAB and 3-mo
• PMID 25869243

• Do labetalol and methyldopa have different effects on pregnancy outcome? Analysis of data from the Control of Hypertension In Pregnancy Study (CHIPS) trial.

• Magee LA1,2,3; CHIPS Study Group, von Dadelszen P2,3, Singer J3,4, Lee T4, Rey E5, Ross S6, Asztalos E7,8,9, Murphy KE8,9, Menzies J2, Sanchez J9, Gafni A10, Gruslin A11, Helewa M12, Hutton E13, Koren G7, Lee SK7, Logan AG14, Ganzevoort JW15, Welch R16, Thornton JG17, Moutquin JM18.
• BJOG : an international journal of obstetrics and gynaecology.BJOG.2015 Aug 11. doi: 10.1111/1471-0528.13569. [Epub ahead of print]
• OBJECTIVE: To compare pregnancy outcomes, accounting for allocated group, between methyldopa-treated and labetalol-treated women in the CHIPS Trial (ISRCTN 71416914) of 'less tight' versus 'tight' control of pregnancy hypertension.DESIGN: Secondary analysis of CHIPS Trial cohort.SETTING: Internation
• PMID 26265372

Japanese Journal

• Induction of metamorphosis of pediveliger larvae of the mussel Mytilus galloprovincialis Lamarck, 1819 using neuroactive compounds, KCl, NH4Cl and organic solvents.

• Yang Jin-Long,Satuito Cyril Glenn,Bao Wei-Yang,Kitamura Hitoshi
• Biofouling 24(6), 461-470, 2008-08-12
• … In 24-h exposure assays, alpha-methyldopa at 5 x 10(-5) M and methoxyphenamine at 5 x 10(-5)-10(-4) M induced 55-94% metamorphosis. …
• NAID 120001779926

• 硫酸マグネシウム大量投与とα-メチルドパの併用が有効であった重症破傷風の1例

• 堀内 郁雄,藤原 晋次郎,森田 正則,石丸 剛,河野 匡彦,鈴木 幸一郎
• 日本救急医学会雑誌 19(2), 113-118, 2008-02-15
• NAID 10024371955

• Modified high-performance liquid chromatography with electrochemical detection method for plasma measurement of levodopa, 3-O-methyldopa, dopamine, carbidopa and 3,4-dihydroxyphenyl acetic acid

• KARIMI Morvarid,CARL Juanita L.,LOFTIN Susan,PERLMUTTER Joel S.
• Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 836(1), 120-123, 2006-05-19
• NAID 10025783914

Related Links

• Methyldopa - Wikipedia, the free encyclopedia

Methyldopa (L-α-Methyl-3,4-dihydroxyphenylalanine; Aldomet, Aldoril, Dopamet, Dopegyt, etc.) is an alpha-adrenergic agonist (selective for α2-adrenergic receptors) psychoactive drug used as a sympatholytic or antihypertensive. Its use is ...

• Methyldopa: MedlinePlus Drug Information

Methyldopa comes as a tablet and a liquid to take by mouth. It usually is taken two to four times a day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand.

Related Pictures

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★リンクテーブル★

リンク元	「メチルドパ」
拡張検索	「α-methyldopa」

「メチルドパ」

　　[★]

英

methyldopa

ラ

methyldopi

同

αメチルドーパ αメチルドパ (国試)α-メチルドパ alpha-methyldopa

化

メチルドパ水和物

商

アルドメット Aldomet、ユープレスドパ

関

血圧降下剤

[show details]

αメチルドーパ : 約 733 件
αメチルドパ : 約 1,140 件
α-メチルドーパ : 約 733 件
α-メチルドパ : 約 1,140 件

分類

• 中枢性交感神経抑制薬

作用機序

• α2受容体アゴニスト　→　シナプス前膜にあるα受容体に結合し、自己抑制的に作用するはず。
• 血管運動中枢に抑制的に作用して、降圧に働く。

適応

• 高血圧、妊婦、腎障害者に使用可能。妊婦にも使える降圧薬(ほかにヒドララジンがあったなあ)。

副作用

• 溶血性貧血、SLE様作用、Coombs陽性、肝障害、起立性低血圧

GOO.853

• 傾眠、見当識低下　←　脳幹のα2受容体に対する作用
• 口内乾燥　←　延髄の中枢におけるα受容体の抑制。
• 性欲減退、パーキンソン症候群、高プロラクチン血症(女性化乳房や乳汁漏出をきたすのが明白になる程度)　←　中枢神経系に対する作用(ドパミン作動性ニューロンにα-メチルドパミンが蓄積してそうである)
• 洞房結節の機能障害がある患者では重度の徐脈や洞停止

禁忌

• 肝障害

「α-methyldopa」

　　[★]

英

関

• 内因性伝達物質の拮抗薬として働く
• ノルエピネフリンに拮抗
• 代謝によりα-methylepinephrineが生成する