Identification

Name
Methyldopa
Accession Number
DB00968  (APRD01106)
Type
Small Molecule
Groups
Approved
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
  • (S)-(-)-alpha-Methyldopa
  • 3-Hydroxy-alpha-methyl-L-tyrosine
  • Alpha medopa
  • alpha-Methyl dopa
  • alpha-methyl-L-dopa
  • Alphamethyldopa
  • AMD
  • Anhydrous methyldopa
  • L-alpha-Methyldopa
  • L-Methyl Dopa
  • Methyl dopa
  • Methyldopa anhydrous
  • α-Methyl dopa
  • α-methyl-L-dopa
External IDs
Bayer 1440L / J9.247I
Product Ingredients
IngredientUNIICASInChI Key
Methyldopa hydrochloride7PX435DN5A2508-79-4QSRVZCCJDKYRRF-YDALLXLXSA-N
Methyldopa sesquihydrate56LH93261Y41372-08-1YKFCISHFRZHKHY-NGQGLHOPSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Aldomet Ester HCl InjLiquid250 mgIntravenousMerck Frosst Canada & Cie, Merck Frosst Canada & Co.1963-12-312002-07-29Canada
Aldomet Tab 125mgTablet125 mgOralMerck Frosst Canada & Cie, Merck Frosst Canada & Co.1971-12-311998-08-14Canada
Aldomet Tab 250mgTablet250 mgOralMerck Frosst Canada & Cie, Merck Frosst Canada & Co.1963-12-312004-11-12Canada
Aldomet Tab 500mgTablet500 mgOralMerck Frosst Canada & Cie, Merck Frosst Canada & Co.1971-12-311998-08-14Canada
Dopamet Tab 125mgTablet125 mgOralIcn Pharmaceuticals1976-12-312005-04-26Canada
Dopamet Tab 250mgTablet250 mgOralIcn Pharmaceuticals1972-12-312005-04-26Canada
Dopamet Tab 500mgTablet500 mgOralIcn Pharmaceuticals1976-12-312005-04-26Canada
Medimet 250tabTablet250 mgOralMedic Laboratory LtÉe1976-12-311996-09-09Canada
MethyldopaTablet125 mgOralAa Pharma Inc1980-04-02Not applicableCanada
MethyldopaTablet500 mgOralAa Pharma Inc1978-12-31Not applicableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
MethyldopaTablet250 mg/1OralMylan Institutional1998-09-01Not applicableUs
MethyldopaTablet, film coated250 mg/1OralRebel Distributors2009-02-23Not applicableUs
MethyldopaTablet250 mg/1OralCardinal Health2011-08-23Not applicableUs
MethyldopaTablet, film coated500 mg/1OralTeva2009-04-28Not applicableUs
MethyldopaTablet, film coated500 mg/1OralAvera Mc Kennan Hospital2016-04-18Not applicableUs
MethyldopaTablet, film coated500 mg/1OralAccord Healthcare Limited2012-06-27Not applicableUs16729 0031 01 nlmimage10 6440b275
MethyldopaTablet, film coated500 mg/1OralA S Medication Solutions2009-04-282017-06-20Us00093 2932 01 nlmimage10 04090248
MethyldopaTablet250 mg/1OralMylan Pharmaceuticals1985-04-18Not applicableUs00378 0611 01 nlmimage10 070903f8
MethyldopaTablet, film coated250 mg/1OralCarilion Materials Management2012-07-24Not applicableUs
MethyldopaTablet, film coated250 mg/1OralTeva2009-02-23Not applicableUs
International/Other Brands
Aldomet / Aldometil / Aldomin / Dopamet / Hypolag / Medomet / Medopren / Novomedopa / Nu-Medopa
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Aldoril 15 TabMethyldopa (250 mg) + Hydrochlorothiazide (15 mg)TabletOralMerck Frosst Canada & Cie, Merck Frosst Canada & Co.1967-12-311998-08-14Canada
Aldoril 25 TabMethyldopa (250 mg) + Hydrochlorothiazide (25 mg)TabletOralMerck Frosst Canada & Cie, Merck Frosst Canada & Co.1963-12-311999-03-02Canada
Apo Methazide 15Methyldopa (250 mg) + Hydrochlorothiazide (15 mg)TabletOralApotex Corporation1984-12-31Not applicableCanada
Apo Methazide 25Methyldopa (250 mg) + Hydrochlorothiazide (25 mg)TabletOralApotex Corporation1984-12-31Not applicableCanada
Methyldopa and HydrochlorothiazideMethyldopa (250 mg/1) + Hydrochlorothiazide (15 mg/1)TabletOralMylan Pharmaceuticals1986-01-23Not applicableUs
Methyldopa and HydrochlorothiazideMethyldopa (250 mg/1) + Hydrochlorothiazide (25 mg/1)TabletOralMylan Pharmaceuticals1986-01-23Not applicableUs
Novo-doparil 15 TabMethyldopa (250 mg) + Hydrochlorothiazide (15 mg)TabletOralNovopharm Limited1980-12-312005-08-10Canada
Novo-doparil 25 TabMethyldopa (250 mg) + Hydrochlorothiazide (25 mg)TabletOralNovopharm Limited1980-12-312005-08-10Canada
PMS-dopazide 15 TabMethyldopa (250 mg) + Hydrochlorothiazide (15 mg)TabletOralPharmascience Inc1984-12-312016-10-28Canada
PMS-dopazide-25 TabMethyldopa (250 mg) + Hydrochlorothiazide (25 mg)TabletOralPharmascience Inc1984-12-312016-10-28Canada
Categories
UNII
M4R0H12F6M
CAS number
555-30-6
Weight
Average: 211.2145
Monoisotopic: 211.084457909
Chemical Formula
C10H13NO4
InChI Key
CJCSPKMFHVPWAR-JTQLQIEISA-N
InChI
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
IUPAC Name
(2S)-2-amino-3-(3,4-dihydroxyphenyl)-2-methylpropanoic acid
SMILES
C[[email protected]](N)(CC1=CC=C(O)C(O)=C1)C(O)=O

Pharmacology

Indication

For use in the treatment of hypertension.

Structured Indications
Pharmacodynamics

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.

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.

TargetActionsOrganism
AAlpha-2A adrenergic receptorNot AvailableHuman
UAromatic-L-amino-acid decarboxylaseNot AvailableHuman
Absorption

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

Volume of distribution
Not Available
Protein binding

Low (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.

Route of elimination

Methyldopa 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 life

The plasma half-life of methyldopa is 105 minutes.

Clearance
  • Renal cl=130 mL/min [healthy]
Toxicity

The 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
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineThe risk or severity of hypertension can be increased when 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline is combined with Methyldopa.Experimental
AcebutololMethyldopa may increase the hypotensive activities of Acebutolol.Approved
AcemetacinThe therapeutic efficacy of Methyldopa can be decreased when used in combination with Acemetacin.Approved, Experimental, Investigational
AlfuzosinAlfuzosin may increase the hypotensive activities of Methyldopa.Approved, Investigational
AliskirenMethyldopa may increase the hypotensive activities of Aliskiren.Approved, Investigational
AlprenololAlprenolol may increase the hypotensive activities of Methyldopa.Approved, Withdrawn
AmbrisentanMethyldopa may increase the hypotensive activities of Ambrisentan.Approved, Investigational
AmifostineMethyldopa may increase the hypotensive activities of Amifostine.Approved, Investigational
AmlodipineAmlodipine may increase the hypotensive activities of Methyldopa.Approved
AmphetamineThe risk or severity of hypertension can be increased when Amphetamine is combined with Methyldopa.Approved, Illicit
AtenololAtenolol may increase the hypotensive activities of Methyldopa.Approved
AvanafilAvanafil may increase the antihypertensive activities of Methyldopa.Approved
BarnidipineMethyldopa may increase the antihypertensive activities of Barnidipine.Approved
BenazeprilBenazepril may increase the hypotensive activities of Methyldopa.Approved, Investigational
BendroflumethiazideBendroflumethiazide may increase the hypotensive activities of Methyldopa.Approved
Benzylpenicilloyl PolylysineMethyldopa may decrease effectiveness of Benzylpenicilloyl Polylysine as a diagnostic agent.Approved
BepridilMethyldopa may increase the hypotensive activities of Bepridil.Approved, Withdrawn
BetaxololBetaxolol may increase the hypotensive activities of Methyldopa.Approved
BethanidineBethanidine may increase the hypotensive activities of Methyldopa.Approved
BietaserpineBietaserpine may increase the hypotensive activities of Methyldopa.Experimental
BimatoprostBimatoprost may increase the hypotensive activities of Methyldopa.Approved, Investigational
BisoprololBisoprolol may increase the hypotensive activities of Methyldopa.Approved
BosentanBosentan may increase the hypotensive activities of Methyldopa.Approved, Investigational
BQ-123Methyldopa may increase the hypotensive activities of BQ-123.Investigational
BretyliumMethyldopa may increase the hypotensive activities of Bretylium.Approved
BrimonidineBrimonidine may increase the antihypertensive activities of Methyldopa.Approved
BrofaromineThe risk or severity of hypertension can be increased when Brofaromine is combined with Methyldopa.Experimental
BucindololBucindolol may decrease the vasoconstricting activities of Methyldopa.Investigational
BunazosinBunazosin may decrease the vasoconstricting activities of Methyldopa.Investigational
BupranololMethyldopa may increase the hypotensive activities of Bupranolol.Approved
CabergolineCabergoline may increase the hypertensive and vasoconstricting activities of Methyldopa.Approved
CadralazineCadralazine may increase the hypotensive activities of Methyldopa.Experimental
CafedrineMethyldopa may increase the hypotensive activities of Cafedrine.Investigational
CandesartanMethyldopa may increase the hypotensive activities of Candesartan.Experimental
Candesartan cilexetilCandesartan cilexetil may increase the hypotensive activities of Methyldopa.Approved
CandoxatrilCandoxatril may increase the hypotensive activities of Methyldopa.Experimental
CaptoprilMethyldopa may increase the hypotensive activities of Captopril.Approved
CarteololCarteolol may increase the hypotensive activities of Methyldopa.Approved
CarvedilolCarvedilol may decrease the vasoconstricting activities of Methyldopa.Approved, Investigational
CeliprololMethyldopa may increase the hypotensive activities of Celiprolol.Approved, Investigational
ChlorothiazideChlorothiazide may increase the hypotensive activities of Methyldopa.Approved, Vet Approved
ChlorthalidoneChlorthalidone may increase the hypotensive activities of Methyldopa.Approved
CicletanineMethyldopa may increase the hypotensive activities of Cicletanine.Investigational
CilazaprilMethyldopa may increase the hypotensive activities of Cilazapril.Approved
ClonidineClonidine may increase the hypotensive activities of Methyldopa.Approved
CloranololMethyldopa may increase the hypotensive activities of Cloranolol.Experimental
CryptenamineCryptenamine may increase the hypotensive activities of Methyldopa.Approved
CyclopenthiazideMethyldopa may increase the hypotensive activities of Cyclopenthiazide.Experimental
CyclothiazideCyclothiazide may increase the hypotensive activities of Methyldopa.Approved
DebrisoquinDebrisoquin may increase the hypotensive activities of Methyldopa.Approved, Investigational
DelaprilMethyldopa may increase the hypotensive activities of Delapril.Experimental
DeserpidineMethyldopa may increase the hypotensive activities of Deserpidine.Approved
DiazoxideDiazoxide may increase the hypotensive activities of Methyldopa.Approved
DiethylnorspermineMethyldopa may increase the hypotensive activities of Diethylnorspermine.Investigational
DihydralazineDihydralazine may increase the hypotensive activities of Methyldopa.Investigational
DiltiazemDiltiazem may increase the hypotensive activities of Methyldopa.Approved
DorzolamideDorzolamide may increase the hypotensive activities of Methyldopa.Approved
DoxazosinDoxazosin may decrease the vasoconstricting activities of Methyldopa.Approved
EfonidipineMethyldopa may increase the hypotensive activities of Efonidipine.Approved, Investigational
EnalaprilEnalapril may increase the hypotensive activities of Methyldopa.Approved, Vet Approved
EnalaprilatMethyldopa may increase the hypotensive activities of Enalaprilat.Approved
EndralazineEndralazine may increase the hypotensive activities of Methyldopa.Experimental
EntacaponeThe metabolism of Methyldopa can be decreased when combined with Entacapone.Approved, Investigational
EpanololMethyldopa may increase the hypotensive activities of Epanolol.Experimental
EpoprostenolMethyldopa may increase the hypotensive activities of Epoprostenol.Approved
EprosartanEprosartan may increase the hypotensive activities of Methyldopa.Approved
FelodipineMethyldopa may increase the hypotensive activities of Felodipine.Approved, Investigational
FenoldopamFenoldopam may increase the hypotensive activities of Methyldopa.Approved
Ferulic acidMethyldopa may increase the hypotensive activities of Ferulic acid.Experimental
FosinoprilFosinopril may increase the hypotensive activities of Methyldopa.Approved
FurazolidoneThe risk or severity of hypertension can be increased when Furazolidone is combined with Methyldopa.Approved, Investigational, Vet Approved
GuanabenzGuanabenz may increase the hypotensive activities of Methyldopa.Approved, Investigational
GuanadrelGuanadrel may increase the hypotensive activities of Methyldopa.Approved
GuanazodineMethyldopa may increase the hypotensive activities of Guanazodine.Experimental
GuanethidineMethyldopa may increase the hypotensive activities of Guanethidine.Approved
GuanfacineGuanfacine may increase the hypotensive activities of Methyldopa.Approved, Investigational
GuanoclorMethyldopa may increase the hypotensive activities of Guanoclor.Experimental
GuanoxabenzMethyldopa may increase the hypotensive activities of Guanoxabenz.Experimental
GuanoxanMethyldopa may increase the hypotensive activities of Guanoxan.Experimental
HarmalineThe risk or severity of hypertension can be increased when Harmaline is combined with Methyldopa.Experimental
HexamethoniumMethyldopa may increase the hypotensive activities of Hexamethonium.Experimental
HyaluronidaseHyaluronidase may increase the vasoconstricting activities of Methyldopa.Approved, Investigational
HydralazineHydralazine may increase the hypotensive activities of Methyldopa.Approved
HydrochlorothiazideMethyldopa may increase the hypotensive activities of Hydrochlorothiazide.Approved, Vet Approved
HydroflumethiazideHydroflumethiazide may increase the hypotensive activities of Methyldopa.Approved, Investigational
ImidaprilMethyldopa may increase the hypotensive activities of Imidapril.Investigational
IndapamideIndapamide may increase the hypotensive activities of Methyldopa.Approved
IndenololMethyldopa may increase the hypotensive activities of Indenolol.Withdrawn
IndoraminIndoramin may increase the hypotensive activities of Methyldopa.Withdrawn
IobenguaneThe therapeutic efficacy of Iobenguane can be decreased when used in combination with Methyldopa.Approved, Investigational
IproniazidThe risk or severity of hypertension can be increased when Iproniazid is combined with Methyldopa.Withdrawn
IrbesartanMethyldopa may increase the hypotensive activities of Irbesartan.Approved, Investigational
IsocarboxazidThe risk or severity of hypertension can be increased when Isocarboxazid is combined with Methyldopa.Approved
IsradipineIsradipine may increase the hypotensive activities of Methyldopa.Approved
KetanserinKetanserin may increase the hypotensive activities of Methyldopa.Investigational
LabetalolLabetalol may decrease the vasoconstricting activities of Methyldopa.Approved
LacidipineMethyldopa may increase the hypotensive activities of Lacidipine.Approved, Investigational
LatanoprostLatanoprost may increase the hypotensive activities of Methyldopa.Approved, Investigational
LercanidipineLercanidipine may increase the hypotensive activities of Methyldopa.Approved, Investigational
LinsidomineMethyldopa may increase the hypotensive activities of Linsidomine.Experimental
LisinoprilLisinopril may increase the hypotensive activities of Methyldopa.Approved, Investigational
LithiumThe risk or severity of adverse effects can be increased when Methyldopa is combined with Lithium.Approved
LofexidineMethyldopa may increase the hypotensive activities of Lofexidine.Approved, Investigational
LosartanLosartan may increase the hypotensive activities of Methyldopa.Approved
MacitentanMethyldopa may increase the hypotensive activities of Macitentan.Approved
ManidipineMethyldopa may increase the hypotensive activities of Manidipine.Approved, Investigational
MecamylamineMecamylamine may increase the hypotensive activities of Methyldopa.Approved
MethoserpidineMethyldopa may increase the hypotensive activities of Methoserpidine.Experimental
MethylergometrineMethylergometrine may increase the hypertensive and vasoconstricting activities of Methyldopa.Approved
MethylphenidateMethylphenidate may decrease the antihypertensive activities of Methyldopa.Approved, Investigational
MetipranololMethyldopa may increase the hypotensive activities of Metipranolol.Approved
MetolazoneMetolazone may increase the hypotensive activities of Methyldopa.Approved
MetoprololMetoprolol may increase the hypotensive activities of Methyldopa.Approved, Investigational
MetyrosineMethyldopa may increase the hypotensive activities of Metyrosine.Approved
MibefradilMethyldopa may increase the hypotensive activities of Mibefradil.Investigational, Withdrawn
MinaprineThe risk or severity of hypertension can be increased when Minaprine is combined with Methyldopa.Approved
MinoxidilMinoxidil may increase the hypotensive activities of Methyldopa.Approved
MirodenafilMirodenafil may increase the antihypertensive activities of Methyldopa.Investigational
MoclobemideThe risk or severity of hypertension can be increased when Moclobemide is combined with Methyldopa.Approved
MoexiprilMoexipril may increase the hypotensive activities of Methyldopa.Approved
MolsidomineMolsidomine may increase the hypotensive activities of Methyldopa.Approved, Investigational
MoxonidineMoxonidine may increase the hypotensive activities of Methyldopa.Approved, Investigational
MuzolimineMethyldopa may increase the hypotensive activities of Muzolimine.Experimental
NadololMethyldopa may increase the hypotensive activities of Nadolol.Approved
NaftopidilMethyldopa may increase the hypotensive activities of Naftopidil.Investigational
NebivololMethyldopa may increase the hypotensive activities of Nebivolol.Approved, Investigational
NialamideThe risk or severity of hypertension can be increased when Nialamide is combined with Methyldopa.Withdrawn
NicardipineNicardipine may increase the hypotensive activities of Methyldopa.Approved
NicorandilMethyldopa may increase the hypotensive activities of Nicorandil.Approved, Investigational
NiguldipineMethyldopa may increase the hypotensive activities of Niguldipine.Experimental
NilvadipineMethyldopa may increase the hypotensive activities of Nilvadipine.Approved, Investigational
NimodipineNimodipine may increase the hypotensive activities of Methyldopa.Approved
NisoldipineNisoldipine may increase the hypotensive activities of Methyldopa.Approved
NitrendipineMethyldopa may increase the hypotensive activities of Nitrendipine.Approved, Investigational
NitroprussideNitroprusside may increase the hypotensive activities of Methyldopa.Approved
ObinutuzumabMethyldopa may increase the hypotensive activities of Obinutuzumab.Approved
OlmesartanOlmesartan may increase the hypotensive activities of Methyldopa.Approved, Investigational
OmapatrilatOmapatrilat may increase the hypotensive activities of Methyldopa.Investigational
OxprenololMethyldopa may increase the hypotensive activities of Oxprenolol.Approved
PargylineThe risk or severity of hypertension can be increased when Pargyline is combined with Methyldopa.Approved
PenbutololMethyldopa may increase the hypotensive activities of Penbutolol.Approved, Investigational
PentoliniumMethyldopa may increase the hypotensive activities of Pentolinium.Approved
PentoxifyllinePentoxifylline may increase the hypotensive activities of Methyldopa.Approved, Investigational
PerindoprilPerindopril may increase the hypotensive activities of Methyldopa.Approved
PhenelzineThe risk or severity of hypertension can be increased when Phenelzine is combined with Methyldopa.Approved
PhenoxybenzaminePhenoxybenzamine may increase the hypotensive activities of Methyldopa.Approved
PhentolaminePhentolamine may increase the hypotensive activities of Methyldopa.Approved
PinacidilPinacidil may increase the hypotensive activities of Methyldopa.Withdrawn
PindololPindolol may increase the hypotensive activities of Methyldopa.Approved
PirlindoleThe risk or severity of hypertension can be increased when Pirlindole is combined with Methyldopa.Approved
Platelet Activating FactorMethyldopa may increase the hypotensive activities of Platelet Activating Factor.Experimental
PolythiazideMethyldopa may increase the hypotensive activities of Polythiazide.Approved
PrazosinPrazosin may decrease the vasoconstricting activities of Methyldopa.Approved
ProcarbazineThe risk or severity of hypertension can be increased when Procarbazine is combined with Methyldopa.Approved
PropranololPropranolol may increase the hypotensive activities of Methyldopa.Approved, Investigational
QuinaprilQuinapril may increase the hypotensive activities of Methyldopa.Approved, Investigational
RamiprilRamipril may increase the hypotensive activities of Methyldopa.Approved
RasagilineThe risk or severity of hypertension can be increased when Rasagiline is combined with Methyldopa.Approved
RemikirenRemikiren may increase the hypotensive activities of Methyldopa.Approved
RescinnamineMethyldopa may increase the hypotensive activities of Rescinnamine.Approved
ReserpineReserpine may increase the hypotensive activities of Methyldopa.Approved, Investigational
RilmenidineRilmenidine may increase the hypotensive activities of Methyldopa.Investigational
RiociguatMethyldopa may increase the hypotensive activities of Riociguat.Approved
RituximabMethyldopa may increase the hypotensive activities of Rituximab.Approved
SaprisartanMethyldopa may increase the hypotensive activities of Saprisartan.Experimental
SelegilineThe risk or severity of hypertension can be increased when Selegiline is combined with Methyldopa.Approved, Investigational, Vet Approved
SelexipagMethyldopa may increase the hypotensive activities of Selexipag.Approved
SildenafilSildenafil may increase the antihypertensive activities of Methyldopa.Approved, Investigational
SilodosinSilodosin may decrease the vasoconstricting activities of Methyldopa.Approved
SitaxentanMethyldopa may increase the hypotensive activities of Sitaxentan.Approved, Investigational, Withdrawn
SpiraprilMethyldopa may increase the hypotensive activities of Spirapril.Approved
SpironolactoneSpironolactone may decrease the vasoconstricting activities of Methyldopa.Approved
TadalafilTadalafil may increase the antihypertensive activities of Methyldopa.Approved, Investigational
TalinololMethyldopa may increase the hypotensive activities of Talinolol.Investigational
TamsulosinTamsulosin may decrease the vasoconstricting activities of Methyldopa.Approved, Investigational
TelmisartanTelmisartan may increase the hypotensive activities of Methyldopa.Approved, Investigational
TemocaprilMethyldopa may increase the hypotensive activities of Temocapril.Experimental, Investigational
TerazosinTerazosin may decrease the vasoconstricting activities of Methyldopa.Approved
TerlipressinMethyldopa may increase the hypotensive activities of Terlipressin.Approved, Investigational
Testosterone propionateThe metabolism of Methyldopa can be decreased when combined with Testosterone Propionate.Approved, Vet Approved, Withdrawn
TetrahydropalmatineMethyldopa may increase the hypotensive activities of Tetrahydropalmatine.Investigational
TheodrenalineMethyldopa may increase the hypotensive activities of Theodrenaline.Investigational
TiboloneMethyldopa may increase the hypotensive activities of Tibolone.Approved, Investigational
TicrynafenMethyldopa may increase the hypotensive activities of Ticrynafen.Withdrawn
TimololTimolol may increase the hypotensive activities of Methyldopa.Approved
TolazolineTolazoline may increase the hypotensive activities of Methyldopa.Approved, Vet Approved
TolcaponeThe metabolism of Methyldopa can be decreased when combined with Tolcapone.Approved, Withdrawn
TolonidineMethyldopa may increase the hypotensive activities of Tolonidine.Experimental
ToloxatoneThe risk or severity of hypertension can be increased when Toloxatone is combined with Methyldopa.Approved
TorasemideTorasemide may increase the hypotensive activities of Methyldopa.Approved
TrandolaprilTrandolapril may increase the hypotensive activities of Methyldopa.Approved
Trans-2-PhenylcyclopropylamineThe risk or severity of hypertension can be increased when Trans-2-Phenylcyclopropylamine is combined with Methyldopa.Experimental
TranylcypromineThe risk or severity of hypertension can be increased when Tranylcypromine is combined with Methyldopa.Approved
TravoprostTravoprost may increase the hypotensive activities of Methyldopa.Approved
TreprostinilTreprostinil may increase the hypotensive activities of Methyldopa.Approved, Investigational
TrichlormethiazideMethyldopa may increase the hypotensive activities of Trichlormethiazide.Approved, Vet Approved
TrimazosinTrimazosin may increase the hypotensive activities of Methyldopa.Experimental
TrimethaphanTrimethaphan may increase the hypotensive activities of Methyldopa.Approved, Investigational
UdenafilUdenafil may increase the antihypertensive activities of Methyldopa.Approved, Investigational
UnoprostoneMethyldopa may increase the hypotensive activities of Unoprostone.Approved, Investigational
UrapidilUrapidil may decrease the vasoconstricting activities of Methyldopa.Investigational
ValsartanValsartan may increase the hypotensive activities of Methyldopa.Approved, Investigational
VardenafilVardenafil may increase the antihypertensive activities of Methyldopa.Approved
VincamineMethyldopa may increase the hypotensive activities of Vincamine.Experimental
VinpocetineMethyldopa may increase the hypotensive activities of Vinpocetine.Investigational
XipamideMethyldopa may increase the hypotensive activities of Xipamide.Experimental
XylometazolineMethyldopa may increase the hypotensive activities of Xylometazoline.Approved
YohimbineYohimbine may decrease the antihypertensive activities of Methyldopa.Approved, Vet Approved
ZofenoprilMethyldopa may increase the hypotensive activities of Zofenopril.Experimental
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.

References

Synthesis Reference
US2868818
General References
  1. Mah GT, Tejani AM, Musini VM: Methyldopa for primary hypertension. Cochrane Database Syst Rev. 2009 Oct 7;(4):CD003893. doi: 10.1002/14651858.CD003893.pub3. [PubMed:19821316]
  2. McCoy S, Baldwin K: Pharmacotherapeutic options for the treatment of preeclampsia. Am J Health Syst Pharm. 2009 Feb 15;66(4):337-44. doi: 10.2146/ajhp080104. [PubMed:19202042]
  3. Sica DA: Centrally acting antihypertensive agents: an update. J Clin Hypertens (Greenwich). 2007 May;9(5):399-405. [PubMed:17485976]
  4. van Zwieten PA: Development and trends in the drug treatment of essential hypertension. J Hypertens Suppl. 1992 Dec;10(7):S1-12. [PubMed:1363322]
  5. Rosenthal T, Oparil S: The effect of antihypertensive drugs on the fetus. J Hum Hypertens. 2002 May;16(5):293-8. [PubMed:12082488]
  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:6295709]
  7. van Zwieten PA: Pharmacology of centrally acting hypotensive drugs. Br J Clin Pharmacol. 1980;10 Suppl 1:13S-20S. [PubMed:6104975]
External Links
Human Metabolome Database
HMDB0011754
KEGG Drug
D08205
KEGG Compound
C07194
PubChem Compound
38853
PubChem Substance
46508535
ChemSpider
35562
BindingDB
48449
ChEBI
61058
ChEMBL
CHEMBL459
Therapeutic Targets Database
DAP000226
PharmGKB
PA450453
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Methyldopa
AHFS Codes
  • 24:08.16 — Central Alpha-agonists
FDA label
Download (155 KB)
MSDS
Download (53.4 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableMyalgic Encephalomyelitis (ME) / Orthostatic Intolerance / Postural Tachycardia Syndrome1
1CompletedOtherHealthy Volunteers1
1CompletedTreatmentAge Related Macular Degeneration (ARMD) / Neovascular Maculopathy1
1, 2WithdrawnTreatmentHigh Blood Pressure (Hypertension) / Pregnancy Toxemias / Proteinuria1
2CompletedTreatmentPregnant Women With Mild Preeclampsia1
2Not Yet RecruitingPreventionType1 Diabetes Mellitus1
3Enrolling by InvitationTreatmentAutonomic Nervous System Diseases / Dopamine Beta-Hydroxylase Deficiency / Idiopathic orthostatic hypotension / Orthostatic Intolerance1
4Not Yet RecruitingTreatmentAge Related Macular Degeneration (ARMD) / Diabetic Macular Edema (DME) / Macular Edema (ME) / Retinal Vein Occlusions(RVO)2
4RecruitingPreventionHypertension, Pregnancy-Induced / Prophylaxis of preeclampsia1
4RecruitingTreatmentHypertension in Pregnancy / Preeclampsia1
4Unknown StatusDiagnosticPreeclampsia1
4Unknown StatusTreatmentPreeclampsia1
Not AvailableActive Not RecruitingOtherPregnancy associated hypertension / Prophylaxis of preeclampsia1
Not AvailableCompletedScreeningGlaucoma1
Not AvailableCompletedTreatmentDiabetes, Diabetes Mellitus Type 11
Not AvailableTerminatedTreatmentHigh Blood Pressure (Hypertension)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Dosage forms
FormRouteStrength
LiquidIntravenous250 mg
TabletOral125 mg
TabletOral250 mg/1
TabletOral250 mg
TabletOral500 mg
TabletOral500 mg/1
Tablet, film coatedOral250 mg/1
Tablet, film coatedOral500 mg/1
Injection, solutionIntravenous50 mg/mL
TabletOral
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.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)300 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 FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
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 inhibitorNon-inhibitor0.9369
CYP450 2D6 inhibitorNon-inhibitor0.9491
CYP450 2C19 inhibitorNon-inhibitor0.9233
CYP450 3A4 inhibitorNon-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
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - GC-EI-TOFGC-MSsplash10-001i-0690000000-f54d986a8144f4a79b82
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0g5i-2900000000-2d1c0ec9ad93e208b620

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenylpropanoic acids. These are compounds with a structure containing a benzene ring conjugated to a propanoic acid.
Kingdom
Organic compounds
Super Class
Phenylpropanoids and polyketides
Class
Phenylpropanoic acids
Sub Class
Not Available
Direct Parent
Phenylpropanoic acids
Alternative Parents
D-alpha-amino acids / Amphetamines and derivatives / Phenylpropanes / Catechols / Aralkylamines / 1-hydroxy-4-unsubstituted benzenoids / 1-hydroxy-2-unsubstituted benzenoids / Amino acids / Monocarboxylic acids and derivatives / Carboxylic acids
show 5 more
Substituents
3-phenylpropanoic-acid / Alpha-amino acid / D-alpha-amino acid / Alpha-amino acid or derivatives / Amphetamine or derivatives / Phenylpropane / Catechol / 1-hydroxy-2-unsubstituted benzenoid / Aralkylamine / 1-hydroxy-4-unsubstituted benzenoid
show 20 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
non-proteinogenic L-alpha-amino acid, L-tyrosine derivative (CHEBI:61058)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
General Function
Thioesterase binding
Specific Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazo...
Gene Name
ADRA2A
Uniprot ID
P08913
Uniprot Name
Alpha-2A adrenergic receptor
Molecular Weight
48956.275 Da
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:17139284]
  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:17016423]
  3. Sica DA: Centrally acting antihypertensive agents: an update. J Clin Hypertens (Greenwich). 2007 May;9(5):399-405. [PubMed:17485976]
  4. Kawasaki H: [Centrally acting sympathetic inhibitors for therapy of patients with hypertension]. Nihon Rinsho. 1997 Aug;55(8):2081-5. [PubMed:9284427]
  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:10415926]
  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:8743022]
  7. van Zwieten PA: Development and trends in the drug treatment of essential hypertension. J Hypertens Suppl. 1992 Dec;10(7):S1-12. [PubMed:1363322]
  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:14557373]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Pyridoxal phosphate binding
Specific Function
Catalyzes the decarboxylation of L-3,4-dihydroxyphenylalanine (DOPA) to dopamine, L-5-hydroxytryptophan to serotonin and L-tryptophan to tryptamine.
Gene Name
DDC
Uniprot ID
P20711
Uniprot Name
Aromatic-L-amino-acid decarboxylase
Molecular Weight
53925.815 Da
References
  1. SOURKES TL: Inhibition of dihydroxy-phenylalanine decarboxylase by derivatives of phenylalanine. Arch Biochem Biophys. 1954 Aug;51(2):444-56. [PubMed:13189588]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
O-methyltransferase activity
Specific Function
Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones. Also shortens the biological half-lives of certain neuroactive drugs, like L-DOP...
Gene Name
COMT
Uniprot ID
P21964
Uniprot Name
Catechol O-methyltransferase
Molecular Weight
30036.77 Da
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. doi: 10.1016/j.aquatox.2010.12.016. Epub 2010 Dec 29. [PubMed:21371608]
  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:11058906]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Proton-dependent oligopeptide secondary active transmembrane transporter activity
Specific Function
Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides. May constitute a major route for the absorption of protein digestion end-products.
Gene Name
SLC15A1
Uniprot ID
P46059
Uniprot Name
Solute carrier family 15 member 1
Molecular Weight
78805.265 Da
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:10052994]

Drug created on June 13, 2005 07:24 / Updated on January 22, 2018 10:45