Methyldopa

From Wikipedia, the free encyclopedia
Jump to: navigation, search
Methyldopa
Methyldopa.svg
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)
Routes of
administration
Oral, IV
Legal status
Legal status
Pharmacokinetic data
Bioavailability approximately 50%
Metabolism Hepatic
Biological half-life 105 minutes
Excretion Renal for metabolites
Identifiers
CAS Number 555-30-6 YesY
ATC code C02AB01 (WHO)
C02AB02 (WHO) (racemic)
PubChem CID 38853
CID 40175
IUPHAR/BPS 5217
DrugBank DB00968 YesY
ChemSpider 35562 N
UNII 56LH93261Y YesY
ChEMBL CHEMBL459 N
Chemical data
Formula C10H13NO4
Molar mass 211.215 g/mol
 NYesY (what is this?)  (verify)

Methyldopa (L-α-Methyl-3,4-dihydroxyphenylalanine; Aldomet, Aldoril, Dopamet, Dopegyt, etc.) is a centrally acting antihypertensive agent. It is metabolized to alpha-methylnorepinephrine in the brain, and this compound is thought to activate central alpha-2 adrenergic receptors (Gerber, 1990). Being a selective agonist for α2 adrenergic receptors, psychoactive drug is 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[edit]

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

Side effects[edit]

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:

Rebound/withdrawal[edit]

Rebound hypertension via withdrawal on account of tolerance upon the abrupt discontinuation of methyldopa has been reported.[3]

Mechanism of Action[edit]

Methyldopa has a dual mechanism of action:

Pharmacokinetics[edit]

Methyldopa exhibits variable absorption from the gastrointestinal tract. It is metabolized in the liver and intestines and is excreted in urine.

History[edit]

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.

See also[edit]

References[edit]

  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.