Methyldopa
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| Clinical data | |
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| Trade names | Aldomet, Aldoril, Dopamet, others |
| Other names | α-Methyl-L-DOPA; α-Methyl-levodopa; α-Methyl-DOPA; L-α-Methyl-3,4-dihydroxyphenylalanine |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a682242 |
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| Routes of administration | By mouth, intravenous |
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| Pharmacokinetic data | |
| Bioavailability | ~50% |
| Metabolism | Liver |
| Onset of action | 4–6 hours[1] |
| Elimination half-life | 105 minutes |
| Duration of action | 10–48 hours[1] |
| Excretion | Kidney for metabolites |
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| Chemical and physical data | |
| Formula | C10H13NO4 |
| Molar mass | 211.217 g·mol−1 |
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Methyldopa, also known as α-methyl-L-DOPA and sold under the brand name Aldomet among others, is a medication used for high blood pressure.[1] It is one of the preferred treatments for high blood pressure in pregnancy.[1] For other types of high blood pressure including very high blood pressure resulting in symptoms other medications are typically preferred.[1] It can be given by mouth or injection into a vein.[1] Onset of effects is around 5 hours and they last about a day.[1]
Common side effects include sleepiness.[1] More severe side effects include red blood cell breakdown, liver problems, and allergic reactions.[1] Methyldopa is in the alpha-2 adrenergic receptor agonist family of medication. It works by stimulating the brain to decrease the activity of the sympathetic nervous system.[1]
Methyldopa was discovered in 1960.[2] It is on the World Health Organization's List of Essential Medicines.[3]
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.[4]
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.[5] Side effects may include:
- Psychological[citation needed]
- Depression
- Suicidal ideation
- Nightmares
- Apathy, anhedonia, or dysphoria
- Anxiety, especially social anxiety
- Decreased alertness, awareness, and wakefulness
- Impaired attention and concentration
- Fatigue
- Malaise
- Drowsiness
- Restlessness
- Cognitive and memory impairment
- Derealization or depersonalization, as well as mild psychosis
- Sexual dysfunction including impaired libido, desire, and drive
- Physiological[citation needed]
- Dizziness, lightheadedness, or vertigo
- Miosis or pupil constriction
- Xerostomia or dry mouth
- Gastrointestinal disturbances such as diarrhea or constipation
- Headache or migraine
- Myalgia or muscle aches, arthralgia or joint pain, or paresthesia ("pins and needles")
- Restless legs syndrome (RLS)
- Parkinsonian symptoms such as muscle tremors, rigidity, hypokinesia, or balance or postural instability
- Akathisia, ataxia, dyskinesia, as well as even tardive dyskinesia or dystonia
- Bell's palsy or facial paralysis
- Sexual dysfunction
- Hyperprolactinemia
- Gynecomastia in males, amenorrhoea or absence of menstrual cycles in females
- Bradycardia
- Hypotension
- Orthostatic hypotension
- Hepatitis, hepatotoxicity, or liver dysfunction or damage
- Pancreatitis
- Warm autoimmune hemolytic anemia or deficiency in red blood cells (RBCs)
- Myelotoxicity or bone marrow suppression, potentially leading to thrombocytopenia, blood platelet deficiency, leukopenia, or white blood cell deficiency
- Hypersensitivity (e.g., lupus erythematosus, myocarditis, or pericarditis)
- Lichenoid reactions (e.g., skin lesions or rashes)
- Pallor
Withdrawal
Rebound hypertension via withdrawal on account of tolerance upon the abrupt discontinuation of methyldopa has been reported.[6]
Mechanism of action
The mechanism of action of methyldopa is not fully clear. It may reduce the dopaminergic and serotonergic transmission in the central and peripheral nervous system and it indirectly affects norepinephrine (noradrenaline) synthesis by way of inhibiting dopamine synthesis. Methyldopa acts on alpha-2 adrenergic receptors, which are found on the pre synaptic nerve terminal.[1] This inhibits the release of norepinephrine from the presynaptic neuron.
The S-enantiomer of methyldopa is a competitive inhibitor of the enzyme aromatic L-amino acid decarboxylase (LAAD), which converts L-DOPA into dopamine. L-DOPA can cross the blood–brain barrier and thus methyldopa may have similar effects. LAAD converts it into alpha-methyldopamine, a false precursor to norepinephrine, which in turn reduces synthesis of norepinephrine in the vesicles. Dopamine beta hydroxylase (DBH) converts alpha-methyldopamine into alpha-methylnorepinephrine, which is an agonist of the presynaptic α2-adrenergic receptor causing inhibition of neurotransmitter release.
Methyldopa has been found to be a monoamine depleting agent.[7]
Pharmacokinetics
Maximum decrease in blood pressure occurs 4–6 hours after oral dosage. The half-life of methyldopa is 105 minutes.[8] Methyldopa exhibits variable absorption from the gastrointestinal tract. It is metabolized in the liver and intestines and is excreted in urine.[citation needed]
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.[9] 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.[citation needed]
See also
- Difluoromethyldopa
- D-DOPA (dextrodopa)
- L-DOPA (levodopa; trade names Sinemet, Pharmacopa, 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.)
- MK-872 HCl salt: [55943-64-1]
- α-Methyltyrosine
- α-Methyl-5-hydroxytryptophan
References
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- ^ a b c d e f g h i j k Page Module:Citation/CS1/styles.css has no content."Methyldopa". The American Society of Health-System Pharmacists. Archived from the original on 21 December 2016. Retrieved 8 December 2016.
- ^ Page Module:Citation/CS1/styles.css has no content.Walker RS (2012). Trends and Changes in Drug Research and Development. Springer Science & Business Media. p. 109. ISBN 978-94-009-2659-2. Archived from the original on 2016-09-14.
- ^ Page Module:Citation/CS1/styles.css has no content.World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
- ^ Page Module:Citation/CS1/styles.css has no content.Malha L, Podymow T, August P (2018). "39 - Hypertension in Pregnancy". Hypertension: A Companion to Braunwald's Heart Disease (3rd ed.). Elsevier. pp. 361–373. doi:10.1016/B978-0-323-42973-3.00039-1. ISBN 978-0-323-42973-3.
- ^ Page Module:Citation/CS1/styles.css has no content.Bnf (September 2008). British National Formulary 56. pp. 95–96. ISBN 978-0-85369-778-7.
- ^ Methyldopa (PIM 342) Script error: No such module "webarchive".
- ^ Page Module:Citation/CS1/styles.css has no content.Tung CS, Goldberg MR, Hollister AS, Sweetman BJ, Robertson D (1988). "Depletion of brainstem epinephrine stores by alpha-methyldopa: possible relation to attenuated sympathetic outflow". Life Sci. 42 (23): 2365–2371. doi:10.1016/0024-3205(88)90190-7. PMID 3287081.
- ^ Page Module:Citation/CS1/styles.css has no content."DailyMed - METHYLDOPA tablet, film coated". dailymed.nlm.nih.gov. Retrieved 2022-07-25.
- ^ Page Module:Citation/CS1/styles.css has no content.Mah GT, Tejani AM, Musini VM (October 2009). "Methyldopa for primary hypertension". The Cochrane Database of Systematic Reviews. 2009 (4) CD003893. doi:10.1002/14651858.CD003893.pub3. PMC 7154320. PMID 19821316.
External links
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