Methyldopa

Methyldopa, 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]

Methyldopa
Clinical data
Trade namesAldomet, Aldoril, Dopamet, others
Other namesL-α-Methyl-3,4-dihydroxyphenylalanine
AHFS/Drugs.comMonograph
MedlinePlusa682242
Pregnancy
category
  • AU: A
  • US: B (No risk in non-human studies)
    Routes of
    administration
    by mouth, IV
    ATC code
    Legal status
    Legal status
    Pharmacokinetic data
    Bioavailabilityapproximately 50%
    MetabolismLiver
    Onset of action4 to 6 hrs[1]
    Elimination half-life105 minutes
    Duration of action10 to 48 hrs[1]
    ExcretionKidney for metabolites
    Identifiers
    CAS Number
    PubChem CID
    IUPHAR/BPS
    DrugBank
    ChemSpider
    UNII
    ChEMBL
    CompTox Dashboard (EPA)
    ECHA InfoCard100.008.264
    Chemical and physical data
    FormulaC10H13NO4
    Molar mass211.215 g/mol g·mol−1
    3D model (JSmol)
     NY (what is this?)  (verify)

    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.[1] 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, the most effective and safe medicines needed in a health system.[3] The wholesale cost in the developing world is about US$4.31–9.48 per month.[4] In the United States it costs less than $25 per month.[5]

    Medical uses

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

    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.[6] Side effects may include:

    Rebound/withdrawal

    Rebound hypertension via withdrawal on account of tolerance upon the abrupt discontinuation of methyldopa has been reported.[7]

    Mechanism of action

    The mechanism of action of methyldopa is not fully clear. Although it is a centrally acting sympathomimetic, it does not block reuptake or transporters. It may reduce the dopaminergic and serotonergic transmission in the peripheral nervous system and it indirectly affects norepinephrine (noradrenaline) synthesis.

    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 prescursor 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.

    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.[8] 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.

    See also

    References

    1. "Methyldopa". The American Society of Health-System Pharmacists. Archived from the original on 21 December 2016. Retrieved 8 December 2016.
    2. Walker, S. R. (2012). Trends and Changes in Drug Research and Development. Springer Science & Business Media. p. 109. ISBN 9789400926592. Archived from the original on 2016-09-14.
    3. "WHO Model List of Essential Medicines (19th List)" (PDF). World Health Organization. April 2015. Archived (PDF) from the original on 13 December 2016. Retrieved 8 December 2016.
    4. "Methyldopa". International Drug Price Indicator Guide. Retrieved 8 December 2016.
    5. Hamilton, Richart (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 140. ISBN 9781284057560.
    6. British National Formulary 56. September 2008. pp. 95–96. ISBN 978-0-85369-778-7.
    7. Methyldopa (PIM 342) Archived 2008-03-13 at the Wayback Machine
    8. 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.
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