Methyldopa - Wikipedia, the free encyclopedia

Methyldopa

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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 cat. a drug of choice in PIH
Legal status ℞ Prescription only
Routes Oral, IV
Pharmacokinetic data
Bioavailability approximately 50%
Metabolism Hepatic
Half-life 105 minutes
Excretion Renal for metabolites
Identifiers
CAS number 555-30-6 YesY
ATC code C02AB01
C02AB02 (racemic)
PubChem CID 40175
DrugBank APRD01106
ChemSpider 36713 YesY
UNII 56LH93261Y YesY
ChEMBL CHEMBL459 N
Chemical data
Formula C10H13NO4 
Mol. mass 211.215 g/mol
SMILES eMolecules & PubChem
 N(what is this?)  (verify)

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 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 (also known as pregnancy-induced hypertension (PIH)).

Contents

  • 1 Indications
  • 2 Pharmacology
  • 3 Pharmacokinetics
  • 4 History
  • 5 Side effects
    • 5.1 Rebound/withdrawal
  • 6 See also
  • 7 References

Indications

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

Pharmacology

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.
  • 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.

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.1 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

Rebound/withdrawal

Rebound hypertension via withdrawal on account of tolerance upon the abrupt discontinuation of methyldopa has been reported.2

See also

  • 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.)

References

  1. ^ British National Formulary 56. September 2008. p. 95–96. ISBN 978-0-85369-778-7. 
  2. ^ Methyldopa (PIM 342)


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