- antihypertensive drug (trade name Aldomet) used in the treatment of high blood pressure (同)alpha methyl dopa, Aldomet
|Systematic (IUPAC) name|
|Biological half-life||105 minutes|
|Excretion||Renal for metabolites|
|Molecular mass||211.215 g/mol|
|N (what is this?)|
|Wikimedia Commons has media related to Metyldopa.|
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
- 2 Side effects
- 2.1 Rebound/withdrawal
- 3 See also
- 4 Mechanism of Action
- 5 Pharmacokinetics
- 6 History
- 7 References
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
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:
- 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
- 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
Rebound hypertension via withdrawal on account of tolerance upon the abrupt discontinuation of methyldopa has been reported.
- 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.
Methyldopa exhibits variable absorption from the gastrointestinal tract. It is metabolized in the liver and intestines and is excreted in urine.
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.
- "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)
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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
- 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
- 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
- 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
- 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 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.
- αメチルドーパ αメチルドパ (国試)α-メチルドパ alpha-methyldopa
- アルドメット Aldomet、ユープレスドパ
- 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。
- 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)