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Medication used to treat high blood pressure
Methyldopa
Trade names Aldomet, Aldoril, Dopamet, others Other names L -α-Methyl-3,4-dihydroxyphenylalanine
AHFS /
Drugs.com
Monograph
MedlinePlus
a682242
License data
Pregnancy category
Routes of administration
By mouth ,
intravenous
ATC code
Legal status
Bioavailability approximately 50%
Metabolism
Liver
Onset of action 4 to 6 hrs
[1]
Elimination half-life 105 minutes
Duration of action 10 to 48 hrs
[1]
Excretion
Kidney for metabolites
(S )-2-amino-3-(3,4-dihydroxyphenyl)-2-methyl-propanoic acid
CAS Number
PubChem
CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (
EPA )
ECHA InfoCard
100.008.264
Formula C 10 H 13 N O 4
Molar mass 211.217 g·mol−1 3D model (
JSmol )
C[C@](N)(Cc1ccc(O)c(O)c1)C(=O)O
InChI=1S/C10H13NO4/c1-10(11,9(14)15)5-6-2-3-7(12)8(13)4-6/h2-4,12-13H,5,11H2,1H3,(H,14,15)/t10-/m0/s1
N Key:CJCSPKMFHVPWAR-JTQLQIEISA-N
N
N Y
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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]
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 :
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
Depression or even
suicidal ideation , as well as
nightmares
Apathy 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 or
malaise or
lassitude
Sedation or
drowsiness or
somnolence or
sleepiness
Agitation or
restlessness
Cognitive and memory impairment
Derealization 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 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 consisting of impaired
erectile dysfunction or
anorgasmia
Hyperprolactinemia or excess
prolactin ,
gynecomastia /breast enlargement in
males , 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
Warm autoimmune hemolytic anemia or
deficiency in
red blood cells (RBCs)
Myelotoxicity or
bone marrow suppression , potentially leading to
thrombocytopenia or
blood platelet
deficiency or
leukopenia or
white blood cell (WBC)
deficiency
Hypersensitivity such as
lupus erythematosus ,
myocarditis , or
pericarditis
Lichenoid reactions such as
skin lesions or
rashes
Pallor
Rebound/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. 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. Methyldopa acts on
alpha-2 adrenergic receptors , which are found on the pre synaptic nerve terminal.
[1] This inhibits the synthesis of
norepinephrine by inhibiting
tyrosine hydroxylase .
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
Maximum decrease in blood pressure occurs 4-6 hours after oral dosage. The half-life of methyldopa is 105 minutes.
[7] 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
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.)
References
External links
Wikimedia Commons has media related to
Methyldopa .
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