Drug/Small Molecule:
l-methyldopa

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PharmGKB contains no Clinical Variants that meet the highest level of criteria.

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The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

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This is a non-comprehensive list of genetic tests with pharmacogenetics relevance, typically submitted by the manufacturer and manually curated by PharmGKB. The information listed is provided for educational purposes only and does not constitute an endorsement of any listed test or manufacturer.

A more complete listing of genetic tests is found at the Genetic Testing Registry (GTR).

PGx Test Variants Assayed Gene?
2D structure from PubChem
provided by PubChem

Overview

Generic Names
  • AMD
  • Alpha medopa
  • Alphamethyldopa
  • L-Methyl Dopa
  • Methyldopa anhydrous
  • Methyldopate
  • Methyldopate HCL
  • Mk. b51
Trade Names
  • Aldoclor-150
  • Aldoclor-250
  • Aldomet
  • Aldometil
  • Aldomin
  • Aldoril 15
  • Aldoril 25
  • Aldoril D30
  • Aldoril D50
  • Apo-Methyldopa
  • Bayer 1440 L
  • Baypresol
  • Becanta
  • Dopamet
  • Dopamethyperpax
  • Dopatec
  • Dopegyt
  • Grospisk
  • Hyperpax
  • Hypolag
  • Medomet
  • Medopa
  • Medopal
  • Medopren
  • Methoplain
  • Novomedopa
  • Nu-Medopa
  • Presinol
  • Presolisin
  • Sedometil
  • Sembrina
Brand Mixture Names
  • Aldoril 15 Tab (Hydrochlorothiazide + Methyldopa)
  • Aldoril 25 Tab (Hydrochlorothiazide + Methyldopa)
  • Apo Methazide 15 (Hydrochlorothiazide + Methyldopa)
  • Apo Methazide 25 (Hydrochlorothiazide + Methyldopa)
  • Novo-Doparil 15 Tab (Hydrochlorothiazide + Methyldopa)
  • Novo-Doparil 25 Tab (Hydrochlorothiazide + Methyldopa)
  • Pms-Dopazide 15 Tab (Hydrochlorothiazide + Methyldopa)
  • Pms-Dopazide-25 Tab (Hydrochlorothiazide + Methyldopa)
  • Supres 150 Tab (Chlorothiazide + Methyldopa)
  • Supres 250 Tab (Chlorothiazide + Methyldopa)

PharmGKB Accession Id:
PA450453

Description

An alpha-2 adrenergic agonist that has both central and peripheral nervous system effects. Its primary clinical use is as an antihypertensive agent.

Source: Drug Bank

Indication

For use in the treatment of hypertension.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

Although the mechanism of action has yet to be conclusively demonstrated, the resultant hypotensive effect is most likely due to the drug's action on the CNS. Methyldopa is converted into the metabolite, alpha-methylnorepinephrine, in the CNS, where it stimulates the central inhibitory alpha-adrenergic receptors, leading to a reduction in sympathetic tone, total peripheral resistance, and blood pressure. Reduction in plasma renin activity, as well as the inhibition of both central and peripheral norepinephrine and serotonine production may also contribute to the drug's antihypertensive effect, although this is not a major mechanism of action. This is done through the inhibition of the decarboxylation of dihydroxyphenylalanine (dopa)-the precursor of norepinephrine-and of 5-hydroxytryptophan (5-HTP)-the precursor of serotonin-in the CNS and in most peripheral tissues.

Source: Drug Bank

Pharmacology

Methyldopa is an aromatic-amino-acid decarboxylase inhibitor in animals and in man. Only methyldopa, the L-isomer of alpha-methyldopa, has the ability to inhibit dopa decarboxylase and to deplete animal tissues of norepinephrine. In man the antihypertensive activity appears to be due solely to the L-isomer. About twice the dose of the racemate (DL-alpha-methyldopa) is required for equal antihypertensive effect. Methyldopa has no direct effect on cardiac function and usually does not reduce glomerular filtration rate, renal blood flow, or filtration fraction. Cardiac output usually is maintained without cardiac acceleration. In some patients the heart rate is slowed. Normal or elevated plasma renin activity may decrease in the course of methyldopa therapy. Methyldopa reduces both supine and standing blood pressure. Methyldopa usually produces highly effective lowering of the supine pressure with infrequent symptomatic postural hypotension. Exercise hypotension and diurnal blood pressure variations rarely occur.

Source: Drug Bank

Food Interaction

Avoid alcohol.|No iron, zinc or fluoride within 2 hours of taking this medication.|May take Vitamin D.|Increase dietary intake of magnesium, folate, vitamin B6, B12, and/or consider taking a multivitamin.|Take without regard to meals.|Avoid natural licorice.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic, extensively metabolized. The known urinary metabolites are: a-methyldopa mono-0-sulfate; 3-0-methyl-a-methyldopa; 3,4-dihydroxyphenylacetone; a-methyldopamine; 3-0-methyl-a-methyldopamine and their conjugates.

Source: Drug Bank

Protein Binding

Low (less than 20%).

Source: Drug Bank

Absorption

Absorption from the gastrointestinal tract is variable but averages approximately 50%.

Source: Drug Bank

Half-Life

The plasma half-life of methyldopa is 105 minutes.

Source: Drug Bank

Toxicity

The oral LD 50 of methyldopa is greater than 1.5 g/kg in both the mouse and the rat. Symptoms of overdose include bloating, constipation, diarrhea, dizziness, extreme drowsiness, gas, light-headedness, nausea, severely low blood pressure, slow heartbeat, vomiting, and weakness.

Source: Drug Bank

Clearance

Source: Drug Bank

Route of Elimination

Methyldopa is extensively metabolized. The known urinary metabolites are: alpha-methyldopa mono-O-sulfate; 3-0-methyl-alpha-methyldopa; 3,4-dihydroxyphenylacetone; alpha-methyldopamine; 3-0-methyl-alpha-methyldopamine and their conjugates. Approximately 70 percent of the drug which is absorbed is excreted in the urine as methyldopa and its mono-O-sulfate conjugate. Methyldopa crosses the placental barrier, appears in cord blood, and appears in breast milk.

Source: Drug Bank

Chemical Properties

Chemical Formula

C10H13NO4

Source: Drug Bank

Isomeric SMILES

C[C@](Cc1ccc(c(c1)O)O)(C(=O)O)N

Source: OpenEye

Canonical SMILES

C[C@](N)(CC1=CC(O)=C(O)C=C1)C(O)=O

Source: Drug Bank

Average Molecular Weight

211.2145

Source: Drug Bank

Monoisotopic Molecular Weight

211.084457909

Source: Drug Bank

Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.

Drug Targets

Gene Description
ADRA2A (source: Drug Bank)

Drug Interactions

Drug Description
l-methyldopa Increased arterial pressure (source: Drug Bank)
l-methyldopa Increased arterial pressure (source: Drug Bank)
l-methyldopa Methyldopa increases haloperidol effect or risk of psychosis (source: Drug Bank)
carteolol Possible hypertensive crisis (source: Drug Bank)
dobutamine Increased arterial pressure (source: Drug Bank)
dobutamine Increased arterial pressure (source: Drug Bank)
dopamine Increased arterial pressure (source: Drug Bank)
dopamine Increased arterial pressure (source: Drug Bank)
entacapone Entacapone increases the effect and toxicity of the sympathomimetic agent, methyldopa. (source: Drug Bank)
ephedra Increased arterial pressure (source: Drug Bank)
ephedrine Increased arterial pressure (source: Drug Bank)
ephedrine Increased arterial pressure (source: Drug Bank)
epinephrine Increased arterial pressure (source: Drug Bank)
epinephrine Increased arterial pressure (source: Drug Bank)
fenoterol Increased arterial pressure (source: Drug Bank)
fenoterol Increased arterial pressure (source: Drug Bank)
haloperidol Methyldopa increases haloperidol effect or risk of psychosis (source: Drug Bank)
haloperidol Methyldopa increases haloperidol effect or risk of psychosis (source: Drug Bank)
iron Iron decreases the absorption of dopa derivatives (source: Drug Bank)
iron Iron decreases the absorption of dopa derivatives (source: Drug Bank)
isoproterenol Increased arterial pressure (source: Drug Bank)
isoproterenol Increased arterial pressure (source: Drug Bank)
levodopa Methyldopa increases the effect and toxicity of levodopa (source: Drug Bank)
levodopa Methyldopa increases the effect and toxicity of levodopa (source: Drug Bank)
lithium Signs of increased lithium levels without increase with this combination (source: Drug Bank)
lithium Signs of increased lithium levels without increase with this combination (source: Drug Bank)
mephentermine Increased arterial pressure (source: Drug Bank)
metaraminol Increased arterial pressure (source: Drug Bank)
methoxamine Increased arterial pressure (source: Drug Bank)
methoxamine Increased arterial pressure (source: Drug Bank)
nadolol Possible hypertensive crisis (source: Drug Bank)
nadolol Possible hypertensive crisis (source: Drug Bank)
norepinephrine Increased arterial pressure (source: Drug Bank)
norepinephrine Increased arterial pressure (source: Drug Bank)
orciprenaline Increased arterial pressure (source: Drug Bank)
orciprenaline Increased arterial pressure (source: Drug Bank)
oxprenolol Possible hypertensive crisis (source: Drug Bank)
oxprenolol Possible hypertensive crisis (source: Drug Bank)
penbutolol Possible hypertensive crisis (source: Drug Bank)
phenylephrine Increased arterial pressure (source: Drug Bank)
phenylephrine Increased arterial pressure (source: Drug Bank)
phenylpropanolamine Increased arterial pressure (source: Drug Bank)
pindolol Possible hypertensive crisis (source: Drug Bank)
pindolol Possible hypertensive crisis (source: Drug Bank)
pirbuterol Increased arterial pressure (source: Drug Bank)
pirbuterol Increased arterial pressure (source: Drug Bank)
procaterol Increased arterial pressure (source: Drug Bank)
propranolol Possible hypertensive crisis (source: Drug Bank)
propranolol Possible hypertensive crisis (source: Drug Bank)
pseudoephedrine Increased arterial pressure (source: Drug Bank)
pseudoephedrine Increased arterial pressure (source: Drug Bank)
salbutamol Increased arterial pressure (source: Drug Bank)
salbutamol Increased arterial pressure (source: Drug Bank)
sotalol Possible hypertensive crisis (source: Drug Bank)
sotalol Possible hypertensive crisis (source: Drug Bank)
terbutaline Increased arterial pressure (source: Drug Bank)
terbutaline Increased arterial pressure (source: Drug Bank)
timolol Possible hypertensive crisis (source: Drug Bank)
timolol Possible hypertensive crisis (source: Drug Bank)
l-methyldopa Signs of increased lithium without increase with this combination (source: Drug Bank)
l-methyldopa Possible hypertensive crisis (source: Drug Bank)
l-methyldopa Increased arterial pressure (source: Drug Bank)
l-methyldopa Possible hypertensive crisis (source: Drug Bank)
l-methyldopa Increased arterial pressure (source: Drug Bank)
l-methyldopa Possible hypertensive crisis (source: Drug Bank)
l-methyldopa Possible hypertensive crisis (source: Drug Bank)
l-methyldopa Increased arterial pressure (source: Drug Bank)
l-methyldopa Increased arterial pressure (source: Drug Bank)
l-methyldopa Possible hypertensive crisis (source: Drug Bank)
No related diseases are available

Publications related to l-methyldopa: 2

No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenetics of antihypertensive drug responses. American journal of pharmacogenomics : genomics-related research in drug development and clinical practice. 2004. Schwartz Gary L, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Catechol-O-methyltransferase activity: a determinant of levodopa response. Clinical pharmacology and therapeutics. 1980. Reilly D K, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
0378-0611-01
DrugBank:
DB00968
ChEBI:
61058
KEGG Compound:
C07194
KEGG Drug:
D08205
PubChem Compound:
38853
PubChem Substance:
46508535
9403
Drugs Product Database (DPD):
426830
ChemSpider:
35562
Therapeutic Targets Database:
DAP000226
FDA Drug Label at DailyMed:
bb1c7c3f-9e6f-4d0e-aea1-6974558659ef

Clinical Trials

These are trials that mention l-methyldopa and are related to either pharmacogenetics or pharmacogenomics.

Common Searches

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Sources for PharmGKB drug information: DrugBank, Open Eye Scientific Software.