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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/02/07 18:00:15」(JST)

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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.^[1]

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.^[2] 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.^[3]

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. Additionally, it has yet to be associated with reducing adverse cardiovascular events including myocardial infarction and stroke, or overall all-cause mortality reduction in clinical trials.^[4] 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

^ "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014.
^ British National Formulary 56. September 2008. pp. 95–96. ISBN 978-0-85369-778-7.
^ Methyldopa (PIM 342)
^ Mah GT, Tejani AM, Musini VM. Methyldopa for primary hypertension. Cochrane Database of Systematic Reviews 2009, Issue 4. Art. No.: CD003893. DOI: 10.1002/14651858.CD003893.pub3.

UpToDate Contents

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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

Adsorptive stripping voltammetry determination of methyldopa on the surface of a carboxylated multiwall carbon nanotubes modified glassy carbon electrode in biological and pharmaceutical samples.

Rezaei B, Askarpour N, Ensafi AA.SourceDepartment of Chemistry, Isfahan University of Technology, Isfahan 8415683111, Islamic Republic of Iran. Electronic address: rezaei@cc.iut.ac.ir.
Colloids and surfaces. B, Biointerfaces.Colloids Surf B Biointerfaces.2013 Sep 1;109:253-8. doi: 10.1016/j.colsurfb.2013.04.004. Epub 2013 Apr 17.
In the present work, a simple carboxylated multiwall carbon nanotubes (CMWCNTs) modified glassy carbon electrode was developed for sensitive determination of methyldopa (MTD). The study of modified electrode and MTD electrochemical behavior at its surface was investigated employing SEM, adsorptive s
PMID 23665091

Systematic review of the effects of maternal hypertension in pregnancy and antihypertensive therapies on child neurocognitive development.

Koren G.SourceMotherisk Program, Division of Clinical Pharmacology, Department of Pediatrics, Hospital for Sick Children and University of Toronto, 555 Univeristy Ave, Toronto, ON M5G 1X8, Canada. Electronic address: gkoren@sickkids.ca.
Reproductive toxicology (Elmsford, N.Y.).Reprod Toxicol.2013 Aug;39:1-5. doi: 10.1016/j.reprotox.2013.03.006. Epub 2013 Mar 28.
As many as 15% of women experience hypertension during pregnancy. Large proportions of them are receiving antihypertensive medications. This review investigated whether hypertension itself, or the antihypertensive medications, adversely affect long term child neurocognitive development. The existing
PMID 23542230

A single oral dose of fructose induces some features of metabolic syndrome in rats: Role of oxidative stress.

Moreno JA, Hong E.SourceFaculty of Medicine, UNAM, Coyoacán DF 04510, Mexico; Department of Pharmacobiology, CINVESTAV IPN, Calzada de los Tenorios 235, 14330 Granjas Coapa, Tlalpan DF, Mexico. Electronic address: acuarioauro@hotmail.com.
Nutrition, metabolism, and cardiovascular diseases : NMCD.Nutr Metab Cardiovasc Dis.2013 Jun;23(6):536-42. doi: 10.1016/j.numecd.2011.10.008. Epub 2012 Mar 2.
BACKGROUND AND AIMS: To determine if a single oral dose of fructose to rats reproduces some features of metabolic syndrome observed after chronic administration and if so, to investigate its mechanisms.METHODS AND RESULTS: Systolic blood pressure was measured in rats before and after oral administra
PMID 22386006

Japanese Journal

薬剤性血液障害:—東北地区—

福田光之
臨床血液 32(7), 725-728, 1991
東北7県で134例収集した。50歳以上の例が全体の57%で性差はなかった。血球別例数は白血球減少51例，血小板減少32例，貧血9例で溶血性が7例，赤血球癆が2例であった。被疑薬は中枢神経用薬49例，循環器用薬25例，抗菌剤48例であった。白血球減少症ではブレンディール5例，メルカゾール11例で，抗生剤14例の多くはペニシリン-セフェム系薬であった。血小板減少症では，H<sub>2&lt …
NAID 130004499760

肝内胆管の破壊性病変及び肉芽しゅを認めた薬剤性肝障害の１生検例

高橋仁公,高木均,市川邦男,長嶺竹明,下條宏,須賀勝久,小林節雄,長坂一三,山田昇司,竹沢二郎,阿部毅彦,佐伯俊一,桜井誠司,山田俊彦,湯浅圭一朗,新井孝之
肝臓 27(5), 636-641, 1986
クロールプロマジン及びアルドメット服用後,肝機能異常が現われ,肝生検にて著明な肝内胆管病変を呈した症例を経験した.症例は71歳,女性で,クロールプロマジンを約18カ月,アルドメットを1カ月服用後肝障害が現われた.肝組織では肝内胆管の破壊像が認められ,同一門脈域に類上皮細胞肉芽腫及びリンパ濾胞を形成する多数の炎症細胞浸潤が認められたが,胆汁うっ滞の所見は認められなかった.組織上では原発性胆汁性肝硬変 …
NAID 130000880963

診療 : Methydopa (Aldomet[○!R]) により肝障害をきたした重症妊娠中毒症の1例

水上尚典,大草尚,木村孔三,玉田太朗,広田紀男
日本産科婦人科學會雜誌 38(1), 139-142, 1986
NAID 110002191076

「メチルドパ」

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
ATC code	C02AB01; C02AB02 (racemic)
PubChem	CID 38853; CID 40175
IUPHAR/BPS	5217
DrugBank	DB00968
ChemSpider	35562
UNII	56LH93261Y
ChEMBL	CHEMBL459
Chemical data
Formula	C10H13NO4
Molar 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 ; Key:CJCSPKMFHVPWAR-JTQLQIEISA-N ;
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　　[★]

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

[1] "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014.

[2] British National Formulary 56. September 2008. pp. 95–96. ISBN 978-0-85369-778-7.

[3] Methyldopa (PIM 342)

[4] Mah GT, Tejani AM, Musini VM. Methyldopa for primary hypertension. Cochrane Database of Systematic Reviews 2009, Issue 4. Art. No.: CD003893. DOI: 10.1002/14651858.CD003893.pub3.

匿名

検索

案内

案内

Aldomet