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Identification
NameMethyldopa
Accession NumberDB00968  (APRD01106)
TypeSmall Molecule
GroupsApproved
Description

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

Structure
Thumb
Synonyms
SynonymLanguageCode
(S)-(-)-alpha-MethyldopaNot AvailableNot Available
3-Hydroxy-alpha-methyl-L-tyrosineNot AvailableNot Available
Alpha medopaNot AvailableNot Available
alpha-Methyl dopaNot AvailableNot Available
AlphamethyldopaNot AvailableNot Available
AMDNot AvailableNot Available
L-alpha-MethyldopaNot AvailableNot Available
L-Methyl DopaNot AvailableNot Available
α-methyl-L-dopaNot AvailableNot Available
Prescription ProductsNot Available
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Methyldopatablet, film coated250 mgoralTeva Pharmaceuticals USA Inc2009-02-23Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Methyldopatablet, film coated500 mgoralTeva Pharmaceuticals USA Inc2009-04-28Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Methyldopatablet500 mgoralMylan Pharmaceuticals Inc.1985-04-18Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Methyldopatablet250 mgoralMylan Pharmaceuticals Inc.1985-04-18Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Methyldopatablet, film coated125 mgoralAccord Healthcare Inc.2012-06-27Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Methyldopatablet, film coated250 mgoralAccord Healthcare Inc.2012-06-27Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Methyldopatablet, film coated500 mgoralAccord Healthcare Inc.2012-06-27Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Methyldopatablet, film coated250 mgoralRebel Distributors Corp1984-02-20Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Methyldopatablet, film coated500 mgoralRebel Distributors Corp1984-02-20Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Methyldopatablet, film coated250 mgoralRebel Distributors Corp2009-02-23Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Methyldopatablet250 mgoralMylan Institutional Inc.2012-12-12Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Methyldopatablet500 mgoralMylan Institutional Inc.2012-12-12Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Methyldopatablet250 mgoralREMEDYREPACK INC.2012-09-25Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Methyldopatablet, film coated500 mgoralA S Medication Solutions Llc2009-04-28Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Methyldopatablet, film coated250 mgoralPhysicians Total Care, Inc.1995-08-29Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Methyldopatablet, film coated500 mgoralPhysicians Total Care, Inc.1996-07-26Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Methyldopatablet250 mgoralCardinal Health2011-08-23Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Methyldopatablet125 mgoralAa Pharma IncNot AvailableNot AvailableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Methyldopatablet250 mgoralAa Pharma IncNot AvailableNot AvailableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Methyldopatablet500 mgoralAa Pharma IncNot AvailableNot AvailableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Over the Counter ProductsNot Available
International Brands
NameCompany
AldometNot Available
AldometilNot Available
AldominNot Available
DopametNot Available
HypolagNot Available
MedometNot Available
MedoprenNot Available
NovomedopaNot Available
Nu-MedopaNot Available
Brand mixtures
Brand NameIngredients
AldoclorChlorothiazide + Methyldopa
AldorilHydrochlorothiazide + Methyldopa
Apo MethazideHydrochlorothiazide + Methyldopa
Novo-DoparilHydrochlorothiazide + Methyldopa
PMS-DopazideHydrochlorothiazide + Methyldopa
SupresChlorothiazide + Methyldopa
Salts
Name/CASStructureProperties
Methyldopa sesquihydrate
ThumbNot applicableDBSALT000988
Categories
CAS number555-30-6
WeightAverage: 211.2145
Monoisotopic: 211.084457909
Chemical FormulaC10H13NO4
InChI KeyCJCSPKMFHVPWAR-UEQNJFAPNA-N
InChI
InChI=1/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-/s2
IUPAC Name
(2S)-2-amino-3-(3,4-dihydroxyphenyl)-2-methylpropanoic acid
SMILES
C[C@](N)(CC1=CC=C(O)C(O)=C1)C(O)=O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as catecholamines and derivatives. These are compounds containing 4-(2-Aminoethyl)pyrocatechol [4-(2-aminoethyl)benzene-1,2-diol] or a derivative thereof formed by substitution.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassPhenols and derivatives
Direct ParentCatecholamines and derivatives
Alternative Parents
Substituents
  • 3-phenylpropanoic-acid
  • Catecholamine
  • L-alpha-amino acid
  • D-alpha-amino acid
  • Amphetamine or derivatives
  • Alpha-amino acid or derivatives
  • Alpha-amino acid
  • Phenylpropane
  • Aralkylamine
  • Amino fatty acid
  • Fatty acyl
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Primary aliphatic amine
  • Carbonyl group
  • Amine
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Pharmacology
IndicationFor use in the treatment of hypertension.
PharmacodynamicsMethyldopa 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.
Mechanism of actionAlthough 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.
AbsorptionAbsorption from the gastrointestinal tract is variable but averages approximately 50%.
Volume of distributionNot Available
Protein bindingLow (less than 20%).
Metabolism

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.

SubstrateEnzymesProduct
Methyldopa
Not Available
3-O-methyl-a-methyldopaDetails
Methyldopa
Not Available
3-O-methyl-a-methyldopamineDetails
Methyldopa
Not Available
a-methyldopa mono-0-sulfateDetails
Methyldopa
Not Available
a-methyldopamineDetails
Route of eliminationMethyldopa is extensively metabolized. The known urinary metabolites are: α-methyldopa mono-O-sulfate; 3-0-methyl-α-methyldopa; 3,4-dihydroxyphenylacetone; α-methyldopamine; 3-0-methyl-α-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.
Half lifeThe plasma half-life of methyldopa is 105 minutes.
Clearance
  • Renal cl=130 mL/min [healthy]
ToxicityThe oral LD50 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.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9374
Blood Brain Barrier-0.9276
Caco-2 permeable-0.8957
P-glycoprotein substrateSubstrate0.6066
P-glycoprotein inhibitor INon-inhibitor0.9852
P-glycoprotein inhibitor IINon-inhibitor0.9895
Renal organic cation transporterNon-inhibitor0.9357
CYP450 2C9 substrateNon-substrate0.7757
CYP450 2D6 substrateNon-substrate0.8
CYP450 3A4 substrateNon-substrate0.6053
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 substrateNon-inhibitor0.9369
CYP450 2D6 substrateNon-inhibitor0.9491
CYP450 2C19 substrateNon-inhibitor0.9233
CYP450 3A4 substrateNon-inhibitor0.864
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9551
Ames testNon AMES toxic0.8185
CarcinogenicityNon-carcinogens0.8997
BiodegradationNot ready biodegradable0.8077
Rat acute toxicity1.6281 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9939
hERG inhibition (predictor II)Non-inhibitor0.9629
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Tabletoral125 mg
Tabletoral250 mg
Tabletoral500 mg
Tablet, film coatedoral125 mg
Tablet, film coatedoral250 mg
Tablet, film coatedoral500 mg
Prices
Unit descriptionCostUnit
Aldoclor 250-250 mg tablet0.67USD tablet
Methyldopa 500 mg tablet0.67USD tablet
Methyldopa 250 mg tablet0.39USD tablet
Apo-Methyldopa 500 mg Tablet0.27USD tablet
Methyldopate 250 mg/5 ml vial0.24USD ml
Apo-Methyldopa 250 mg Tablet0.15USD tablet
Apo-Methyldopa 125 mg Tablet0.1USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point300 dec °CPhysProp
water solubility1E+004 mg/L (at 25 °C)MERCK INDEX (1996)
logP-1.7Not Available
Predicted Properties
PropertyValueSource
Water Solubility2.26 mg/mLALOGPS
logP-2ALOGPS
logP-1.4ChemAxon
logS-2ALOGPS
pKa (Strongest Acidic)1.73ChemAxon
pKa (Strongest Basic)9.85ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area103.78 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity53.79 m3·mol-1ChemAxon
Polarizability20.73 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
References
Synthesis Reference

DrugSyn.org

US2868818
General Reference
  1. Mah GT, Tejani AM, Musini VM: Methyldopa for primary hypertension. Cochrane Database Syst Rev. 2009 Oct 7;(4):CD003893. Pubmed
  2. McCoy S, Baldwin K: Pharmacotherapeutic options for the treatment of preeclampsia. Am J Health Syst Pharm. 2009 Feb 15;66(4):337-44. Pubmed
  3. Sica DA: Centrally acting antihypertensive agents: an update. J Clin Hypertens (Greenwich). 2007 May;9(5):399-405. Pubmed
  4. van Zwieten PA: Development and trends in the drug treatment of essential hypertension. J Hypertens Suppl. 1992 Dec;10(7):S1-12. Pubmed
  5. Rosenthal T, Oparil S: The effect of antihypertensive drugs on the fetus. J Hum Hypertens. 2002 May;16(5):293-8. Pubmed
  6. van Zwieten PA, Timmermans PB: Pharmacology and characterization of central alpha-adrenoceptors involved in the effect of centrally acting antihypertensive drugs. Chest. 1983 Feb;83(2 Suppl):340-3. Pubmed
  7. van Zwieten PA: Pharmacology of centrally acting hypotensive drugs. Br J Clin Pharmacol. 1980;10 Suppl 1:13S-20S. Pubmed
External Links
ATC CodesNot Available
AHFS Codes
  • 24:08.16
PDB EntriesNot Available
FDA labelDownload (155 KB)
MSDSDownload (53.4 KB)
Interactions
Drug Interactions
Drug
AlfuzosinMay enhance the hypotensive effect of Antihypertensives.
AmifostineAntihypertensives may enhance the hypotensive effect of Amifostine.
BretyliumMay enhance the bradycardic effect of Bradycardia-Causing Agents. Bretylium may also enhance atrioventricular (AV) blockade in patients receiving AV blocking agents.
ButabarbitalMay enhance the hypotensive effect of Hypotensive Agents.
ButethalMay enhance the hypotensive effect of Hypotensive Agents.
DiazoxideMay enhance the hypotensive effect of Antihypertensives.
DuloxetineHypotensive Agents may enhance the orthostatic hypotensive effect of DULoxetine.
HeptabarbitalMay enhance the hypotensive effect of Hypotensive Agents.
HexobarbitalMay enhance the hypotensive effect of Hypotensive Agents.
IobenguaneMay diminish the therapeutic effect of Iobenguane I 123.
IsocarboxazidMAO Inhibitors may enhance the adverse/toxic effect of Methyldopa.
LacosamideBradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide.
LinezolidMAO Inhibitors may enhance the adverse/toxic effect of Methyldopa.
LithiumMethyldopa may enhance the adverse/toxic effect of Lithium. This may occur without notable changes in serum lithium concentrations.
MethohexitalMay enhance the hypotensive effect of Hypotensive Agents.
MethylphenidateMay diminish the antihypertensive effect of Antihypertensives.
MirtazapineMay diminish the antihypertensive effect of Alpha2-Agonists.
MoclobemideMAO Inhibitors may enhance the adverse/toxic effect of Methyldopa.
ObinutuzumabAntihypertensives may enhance the hypotensive effect of Obinutuzumab.
PentobarbitalMay enhance the hypotensive effect of Hypotensive Agents.
PentoxifyllineMay enhance the hypotensive effect of Antihypertensives.
PhenelzineMAO Inhibitors may enhance the adverse/toxic effect of Methyldopa.
PrimidoneMay enhance the hypotensive effect of Hypotensive Agents.
ProcarbazineMAO Inhibitors may enhance the adverse/toxic effect of Methyldopa.
RasagilineMAO Inhibitors may enhance the adverse/toxic effect of Methyldopa.
RisperidoneHypotensive Agents may enhance the hypotensive effect of RisperiDONE.
RituximabAntihypertensives may enhance the hypotensive effect of RiTUXimab.
RuxolitinibMay enhance the bradycardic effect of Bradycardia-Causing Agents.
SecobarbitalMay enhance the hypotensive effect of Hypotensive Agents.
SelegilineMAO Inhibitors may enhance the adverse/toxic effect of Methyldopa.
TadalafilMay enhance the antihypertensive effect of Antihypertensives.
Tedizolid PhosphateMAO Inhibitors may enhance the adverse/toxic effect of Methyldopa.
TofacitinibMay enhance the bradycardic effect of Bradycardia-Causing Agents.
TranylcypromineMAO Inhibitors may enhance the adverse/toxic effect of Methyldopa.
VardenafilMay enhance the antihypertensive effect of Antihypertensives.
YohimbineMay diminish the antihypertensive effect of Antihypertensives.
Food Interactions
  • Avoid alcohol.
  • Avoid natural licorice.
  • Increase dietary intake of magnesium, folate, vitamin B6, B12, and/or consider taking a multivitamin.
  • May take Vitamin D.
  • No iron, zinc or fluoride within 2 hours of taking this medication.
  • Take without regard to meals.

Targets

1. Alpha-2A adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Components

Name UniProt ID Details
Alpha-2A adrenergic receptor P08913 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Sica DA: Centrally acting antihypertensive agents: an update. J Clin Hypertens (Greenwich). 2007 May;9(5):399-405. Pubmed
  4. Kawasaki H: [Centrally acting sympathetic inhibitors for therapy of patients with hypertension] Nippon Rinsho. 1997 Aug;55(8):2081-5. Pubmed
  5. Head GA: Central imidazoline- and alpha 2-receptors involved in the cardiovascular actions of centrally acting antihypertensive agents. Ann N Y Acad Sci. 1999 Jun 21;881:279-86. Pubmed
  6. van Zwieten PA: New central mediators as targets of centrally acting antihypertensive drugs. Clin Exp Hypertens. 1996 Apr-May;18(3-4):291-303. Pubmed
  7. van Zwieten PA: Development and trends in the drug treatment of essential hypertension. J Hypertens Suppl. 1992 Dec;10(7):S1-12. Pubmed
  8. Velliquette RA, Ernsberger P: Contrasting metabolic effects of antihypertensive agents. J Pharmacol Exp Ther. 2003 Dec;307(3):1104-11. Epub 2003 Oct 13. Pubmed

2. Aromatic-L-amino-acid decarboxylase

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Aromatic-L-amino-acid decarboxylase P20711 Details

References:

  1. SOURKES TL: Inhibition of dihydroxy-phenylalanine decarboxylase by derivatives of phenylalanine. Arch Biochem Biophys. 1954 Aug;51(2):444-56. Pubmed

Enzymes

1. Catechol O-methyltransferase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Catechol O-methyltransferase P21964 Details

References:

  1. Alazizi A, Liu MY, Williams FE, Kurogi K, Sakakibara Y, Suiko M, Liu MC: Identification, characterization, and ontogenic study of a catechol O-methyltransferase from zebrafish. Aquat Toxicol. 2011 Mar;102(1-2):18-23. Epub 2010 Dec 29. Pubmed
  2. Ameyaw MM, Syvanen AC, Ulmanen I, Ofori-Adjei D, McLeod HL: Pharmacogenetics of catechol-O-methyltransferase: frequency of low activity allele in a Ghanaian population. Hum Mutat. 2000 Nov;16(5):445-6. Pubmed

Transporters

1. Solute carrier family 15 member 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 15 member 1 P46059 Details

References:

  1. Han HK, Rhie JK, Oh DM, Saito G, Hsu CP, Stewart BH, Amidon GL: CHO/hPEPT1 cells overexpressing the human peptide transporter (hPEPT1) as an alternative in vitro model for peptidomimetic drugs. J Pharm Sci. 1999 Mar;88(3):347-50. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on January 12, 2014 21:19