U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C10H13NO4
Molecular Weight 211.2145
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of METHYLDOPA ANHYDROUS

SMILES

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

InChI

InChIKey=CJCSPKMFHVPWAR-JTQLQIEISA-N
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

HIDE SMILES / InChI

Molecular Formula C10H13NO4
Molecular Weight 211.2145
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Methyldopate hydrochloride [levo-3-(3,4-dihydroxyphenyl)-2-methylalanine, ethyl ester hydrochloride] is the ethyl ester of methyldopa, supplied as the hydrochloride salt with a molecular weight of 275.73. Methyldopate hydrochloride is more soluble and stable in solution than methyldopa and is the preferred form for intravenous use. Methyldopate hydrochloride is an alpha adrenergic agonist that has both central and peripheral nervous system effects. Its primary clinical use is as an antihypertensive agent.

CNS Activity

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
ALDOMET

Approved Use

INDICATION AND USAGE: Hypertension.

Launch Date

1962
Primary
ALDOMET

Approved Use

INDICATION AND USAGE: Hypertension.

Launch Date

1962
Primary
ALDOMET

Approved Use

INDICATION AND USAGE: Hypertension.

Launch Date

1962
Primary
Methyldopate hydrochloride

Approved Use

Hypertension, when parenteral medication is indicated. The treatment of hypertensive crises may be initiated with Methyldopate HCl Injection.

Launch Date

1995
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
771.3 ng/mL
250 mg single, oral
dose: 250 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
METHYLDOPA plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
4.54 μg × h/mL
100 mg single, intravenous
dose: 100 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
METHYLDOPA plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
5352.9 ng × h/mL
250 mg single, oral
dose: 250 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
METHYLDOPA plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
1.28 h
100 mg single, intravenous
dose: 100 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
METHYLDOPA plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
12.6 h
250 mg single, oral
dose: 250 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
METHYLDOPA plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
85%
100 mg single, intravenous
dose: 100 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
METHYLDOPA plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
2.5 g single, oral
Dose: 2.5 g
Route: oral
Route: single
Dose: 2.5 g
Sources:
unknown, 19
n = 1
Health Status: unknown
Age Group: 19
Sex: M
Population Size: 1
Sources:
Other AEs: Coma...
Other AEs:
Coma (grade 1)
Sources:
2326 mg multiple, oral (mean)
Recommended
Dose: 2326 mg
Route: oral
Route: multiple
Dose: 2326 mg
Sources:
unhealthy, 36-68
n = 30
Health Status: unhealthy
Condition: hypertension
Age Group: 36-68
Sex: M+F
Population Size: 30
Sources:
Disc. AE: Depression, Tiredness...
AEs leading to
discontinuation/dose reduction:
Depression (2 patients)
Tiredness (2 patients)
Diarrhoea (1 patient)
Rash (1 patient)
Blackout (1 patient)
Sources:
250 mg 4 times / day multiple, oral
Recommended
Dose: 250 mg, 4 times / day
Route: oral
Route: multiple
Dose: 250 mg, 4 times / day
Sources:
unhealthy
n = 39
Health Status: unhealthy
Condition: hypertension
Sex: M+F
Population Size: 39
Sources:
Other AEs: Somnolence, Dry mouth...
Other AEs:
Somnolence (15 patients)
Dry mouth (12 patients)
Malaise (6 patients)
Constipation (5 patients)
Anorexia (5 patients)
Diarrhoea (3 patients)
Depression (2 patients)
Weight gain (2 patients)
Mental confusion (1 patient)
Postural hypotension (1 patient)
Sources:
AEs

AEs

AESignificanceDosePopulation
Coma grade 1
2.5 g single, oral
Dose: 2.5 g
Route: oral
Route: single
Dose: 2.5 g
Sources:
unknown, 19
n = 1
Health Status: unknown
Age Group: 19
Sex: M
Population Size: 1
Sources:
Blackout 1 patient
Disc. AE
2326 mg multiple, oral (mean)
Recommended
Dose: 2326 mg
Route: oral
Route: multiple
Dose: 2326 mg
Sources:
unhealthy, 36-68
n = 30
Health Status: unhealthy
Condition: hypertension
Age Group: 36-68
Sex: M+F
Population Size: 30
Sources:
Diarrhoea 1 patient
Disc. AE
2326 mg multiple, oral (mean)
Recommended
Dose: 2326 mg
Route: oral
Route: multiple
Dose: 2326 mg
Sources:
unhealthy, 36-68
n = 30
Health Status: unhealthy
Condition: hypertension
Age Group: 36-68
Sex: M+F
Population Size: 30
Sources:
Rash 1 patient
Disc. AE
2326 mg multiple, oral (mean)
Recommended
Dose: 2326 mg
Route: oral
Route: multiple
Dose: 2326 mg
Sources:
unhealthy, 36-68
n = 30
Health Status: unhealthy
Condition: hypertension
Age Group: 36-68
Sex: M+F
Population Size: 30
Sources:
Depression 2 patients
Disc. AE
2326 mg multiple, oral (mean)
Recommended
Dose: 2326 mg
Route: oral
Route: multiple
Dose: 2326 mg
Sources:
unhealthy, 36-68
n = 30
Health Status: unhealthy
Condition: hypertension
Age Group: 36-68
Sex: M+F
Population Size: 30
Sources:
Tiredness 2 patients
Disc. AE
2326 mg multiple, oral (mean)
Recommended
Dose: 2326 mg
Route: oral
Route: multiple
Dose: 2326 mg
Sources:
unhealthy, 36-68
n = 30
Health Status: unhealthy
Condition: hypertension
Age Group: 36-68
Sex: M+F
Population Size: 30
Sources:
Mental confusion 1 patient
250 mg 4 times / day multiple, oral
Recommended
Dose: 250 mg, 4 times / day
Route: oral
Route: multiple
Dose: 250 mg, 4 times / day
Sources:
unhealthy
n = 39
Health Status: unhealthy
Condition: hypertension
Sex: M+F
Population Size: 39
Sources:
Postural hypotension 1 patient
250 mg 4 times / day multiple, oral
Recommended
Dose: 250 mg, 4 times / day
Route: oral
Route: multiple
Dose: 250 mg, 4 times / day
Sources:
unhealthy
n = 39
Health Status: unhealthy
Condition: hypertension
Sex: M+F
Population Size: 39
Sources:
Dry mouth 12 patients
250 mg 4 times / day multiple, oral
Recommended
Dose: 250 mg, 4 times / day
Route: oral
Route: multiple
Dose: 250 mg, 4 times / day
Sources:
unhealthy
n = 39
Health Status: unhealthy
Condition: hypertension
Sex: M+F
Population Size: 39
Sources:
Somnolence 15 patients
250 mg 4 times / day multiple, oral
Recommended
Dose: 250 mg, 4 times / day
Route: oral
Route: multiple
Dose: 250 mg, 4 times / day
Sources:
unhealthy
n = 39
Health Status: unhealthy
Condition: hypertension
Sex: M+F
Population Size: 39
Sources:
Depression 2 patients
250 mg 4 times / day multiple, oral
Recommended
Dose: 250 mg, 4 times / day
Route: oral
Route: multiple
Dose: 250 mg, 4 times / day
Sources:
unhealthy
n = 39
Health Status: unhealthy
Condition: hypertension
Sex: M+F
Population Size: 39
Sources:
Weight gain 2 patients
250 mg 4 times / day multiple, oral
Recommended
Dose: 250 mg, 4 times / day
Route: oral
Route: multiple
Dose: 250 mg, 4 times / day
Sources:
unhealthy
n = 39
Health Status: unhealthy
Condition: hypertension
Sex: M+F
Population Size: 39
Sources:
Diarrhoea 3 patients
250 mg 4 times / day multiple, oral
Recommended
Dose: 250 mg, 4 times / day
Route: oral
Route: multiple
Dose: 250 mg, 4 times / day
Sources:
unhealthy
n = 39
Health Status: unhealthy
Condition: hypertension
Sex: M+F
Population Size: 39
Sources:
Anorexia 5 patients
250 mg 4 times / day multiple, oral
Recommended
Dose: 250 mg, 4 times / day
Route: oral
Route: multiple
Dose: 250 mg, 4 times / day
Sources:
unhealthy
n = 39
Health Status: unhealthy
Condition: hypertension
Sex: M+F
Population Size: 39
Sources:
Constipation 5 patients
250 mg 4 times / day multiple, oral
Recommended
Dose: 250 mg, 4 times / day
Route: oral
Route: multiple
Dose: 250 mg, 4 times / day
Sources:
unhealthy
n = 39
Health Status: unhealthy
Condition: hypertension
Sex: M+F
Population Size: 39
Sources:
Malaise 6 patients
250 mg 4 times / day multiple, oral
Recommended
Dose: 250 mg, 4 times / day
Route: oral
Route: multiple
Dose: 250 mg, 4 times / day
Sources:
unhealthy
n = 39
Health Status: unhealthy
Condition: hypertension
Sex: M+F
Population Size: 39
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer

Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
likely
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
[Use of alpha-methyldopa in the treatment of arterial hypertension].
1975 Aug 31
Delayed hepatotoxicity from methyldopa.
1975 Dec
Persistent parkinsonism following neuroleptanalgesia.
1975 May
Dihydroergotamine: an effective treatment for postural hypotension due to antihypertensive drugs (ganglion-blocking agents excepted).
1976
Some side-effects of alpha-methyldopa.
1976 Apr 10
Drug-associated acute pancreatitis: twenty-one years of spontaneous reporting in The Netherlands.
1999 Sep
Antihypertensive treatment decreased serum leptin levels in severe preeclampsia during pregnancy.
2001
Antihypertensive drug therapy for mild to moderate hypertension during pregnancy.
2001
[Drug-induced hemolytic anemia].
2001 Aug
Effect of methyldopa on renal function in rats with L-NAME-induced hypertension in pregnancy.
2001 Aug
Effect of alpha-methyldopa on pentoxyresorufin O-dealkylation in liver microsomes from rats treated with phenobarbital.
2001 Aug 1
Drugs in pregnancy. Antihypertensives.
2001 Dec
The use of a response surface methodology on HPLC analysis of methyldopa, amiloride and hydrochlorothiazide in tablets.
2001 Mar
Involvement of imidazoline receptors in the baroreflex effects of rilmenidine in conscious rabbits.
2001 Sep
The immune haemolytic anaemias: a century of exciting progress in understanding.
2001 Sep
Excretion of antihypertensive medication into human breast milk: a systematic review.
2002
Methyldopa versus no drug treatment in the management of mild pre-eclampsia.
2002 Apr
Immune-mediated drug-induced liver disease.
2002 Aug
Effects of six anti-hypertensive medications on cognitive performance.
2002 Aug
Relationship between treatment-induced changes in left ventricular mass and blood pressure in black african hypertensive patients: results of the Baragwanath Trial.
2002 Feb 19
Preparation of (R) and (S) alpha methyldopa from a chiral hydantoin containing the alpha phenylethyl group.
2002 Feb-Mar
Brain catecholamine metabolism in catechol-O-methyltransferase (COMT)-deficient mice.
2002 Jan
Rapid-eye-movement sleep in jittery infants.
2002 Jan
Hypertension/preeclampsia.
2002 Jan-Feb
The effect of methyldopa treatment on uterine, umblical and fetal middle cerebral artery blood flows in preeclamptic patients.
2002 Jul
C4 deficiency state in antiphospholipid antibody-related recurrent preeclampsia evolving into systemic lupus erythematosus.
2002 Jul
Determination of antioxidant activity of some drugs using high-pressure liquid chromatography.
2003
Methyldopa supplement for resistant essential hypertension: a prospective randomized placebo control crossover study.
2003 Dec
Blood pressure response to out-patient drug treatment of hypertension in 1973-1993 at Korle-Bu Teaching Hospital, Accra, Ghana.
2003 Jun
Physician gender and antihypertensive prescription pattern in primary care.
2003 Nov
[Centrally-acting antihypertensive drugs].
2004 Mar
[Hypertension in pregnancy].
2004 Mar
Drug-induced liver injury.
2004 Mar 1
Differential modulation by estrogen of alpha2-adrenergic and I1-imidazoline receptor-mediated hypotension in female rats.
2004 Oct
Patents

Sample Use Guides

In Vivo Use Guide
Curator's Comment: When control has been obtained, oral therapy with tablets may be substituted for intravenous therapy, starting with the same dosage schedule used for the parenteral route. The effectiveness and anticipated responses are described in the circular for tablets.
Initial: 250 mg PO q8-12hr for 2 days, increase q2Days PRN Maintenance: 250-1000 mg/day divided q6-12hr PO, usually no more than 3 g/day IV (methyldopate): 250-1000 mg infusion over 30-60 minutes q6-8hr PRN; no more than 4 g/day
Route of Administration: Other
Human uterine microvascular endothelial cells (UtMVEC) (PromoCell, Heidelberg, Germany) were cultured in EGM-2- MV medium (Lonza, Basel, Switzerland) until about 80% confluent. Cells from passage 4-8 were used in this study. Tissue culture plates (24-wells) were coated with undiluted Matrigel (300 μL/well; In Vitro Technologies, Noble Park, Vic., Australia) and polymerized for 30 minutes at 37°C. UtMVECs (100 000 cells/well) were seeded into each well and endothelial cell tubular networks formed within 4 hours of further incubation at 37°C. HTR-8/ SVneo cells (100 000 cells/well) were then added to each well with or without a low dose of TNF-α (0.5 ng/mL) together with methyldopa (5 μg/ mL), labetalol (0.5 μg/mL), hydralazine (10 μg/mL) or clonidine (1.0 μg/ mL) and co-cultured with the endothelial cellular networks. The control co-cultured cells had neither TNF-α nor medications added. After 24 hours of culture, the cells were retrieved from the cellular networks in Matrigel with Cell Recovery Solution (CRS) (In Vitro Technologies) for RNA extraction
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:57:41 GMT 2023
Edited
by admin
on Fri Dec 15 15:57:41 GMT 2023
Record UNII
M4R0H12F6M
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
METHYLDOPA ANHYDROUS
Common Name English
J9.247I
Code English
ANHYDROUS METHYLDOPA
MART.  
Common Name English
(-)-.ALPHA.-METHYLDOPA
Common Name English
L-.ALPHA.-METHYL-3-(3,4)-DIHYDROXYPHENYLALANINE
Common Name English
L-TYROSINE, 3-HYDROXY-.ALPHA.-METHYL-
Systematic Name English
METHYLDOPA (LEVOROTATORY)
Common Name English
BAYER-1440L
Code English
(-)-METHYLDOPA
Systematic Name English
ANHYDROUS METHYLDOPA [MART.]
Common Name English
(-)-.ALPHA.-METHYL-3,4-DIHYDROXYPHENYLALANINE
Systematic Name English
L-.ALPHA.-METHYLDOPA
Common Name English
(2S)-2-AMINO-3-(3,4-DIHYDROXYPHENYL)-2-METHYLPROPANOIC ACID
Systematic Name English
.ALPHA.-METHYL-L-DOPA
Brand Name English
L-3-(3,4-DIHYDROXYPHENYL)-2-METHYLALANINE
Common Name English
Methyldopa [WHO-DD]
Common Name English
METHYL DOPA
Systematic Name English
methyldopa [INN]
Common Name English
METHYLDOPA [MI]
Common Name English
LEDERDOPA
Brand Name English
CARBIDOPA IMPURITY A [EP IMPURITY]
Common Name English
METHYLDOPA [HSDB]
Common Name English
NSC-169916
Code English
METHYLDOPA, ANHYDROUS
Common Name English
.ALPHA.-METHYL-L-3,4-DIHYDROXYPHENYLALANINE
Common Name English
(S)-(-)-.ALPHA.-METHYLDOPA
Common Name English
Classification Tree Code System Code
WHO-ATC C02AB01
Created by admin on Fri Dec 15 15:57:41 GMT 2023 , Edited by admin on Fri Dec 15 15:57:41 GMT 2023
NDF-RT N0000175554
Created by admin on Fri Dec 15 15:57:41 GMT 2023 , Edited by admin on Fri Dec 15 15:57:41 GMT 2023
WHO-ATC C02LB01
Created by admin on Fri Dec 15 15:57:41 GMT 2023 , Edited by admin on Fri Dec 15 15:57:41 GMT 2023
NDF-RT N0000009918
Created by admin on Fri Dec 15 15:57:41 GMT 2023 , Edited by admin on Fri Dec 15 15:57:41 GMT 2023
WHO-ATC C02AB
Created by admin on Fri Dec 15 15:57:41 GMT 2023 , Edited by admin on Fri Dec 15 15:57:41 GMT 2023
Code System Code Type Description
PUBCHEM
38853
Created by admin on Fri Dec 15 15:57:41 GMT 2023 , Edited by admin on Fri Dec 15 15:57:41 GMT 2023
PRIMARY
ECHA (EC/EINECS)
209-089-2
Created by admin on Fri Dec 15 15:57:41 GMT 2023 , Edited by admin on Fri Dec 15 15:57:41 GMT 2023
PRIMARY
RXCUI
1545996
Created by admin on Fri Dec 15 15:57:41 GMT 2023 , Edited by admin on Fri Dec 15 15:57:41 GMT 2023
PRIMARY RxNorm
EVMPD
SUB08867MIG
Created by admin on Fri Dec 15 15:57:41 GMT 2023 , Edited by admin on Fri Dec 15 15:57:41 GMT 2023
PRIMARY
INN
1110
Created by admin on Fri Dec 15 15:57:41 GMT 2023 , Edited by admin on Fri Dec 15 15:57:41 GMT 2023
PRIMARY
DAILYMED
M4R0H12F6M
Created by admin on Fri Dec 15 15:57:41 GMT 2023 , Edited by admin on Fri Dec 15 15:57:41 GMT 2023
PRIMARY
HSDB
218
Created by admin on Fri Dec 15 15:57:41 GMT 2023 , Edited by admin on Fri Dec 15 15:57:41 GMT 2023
PRIMARY
EPA CompTox
DTXSID5023295
Created by admin on Fri Dec 15 15:57:41 GMT 2023 , Edited by admin on Fri Dec 15 15:57:41 GMT 2023
PRIMARY
NCI_THESAURUS
C175729
Created by admin on Fri Dec 15 15:57:41 GMT 2023 , Edited by admin on Fri Dec 15 15:57:41 GMT 2023
PRIMARY
EVMPD
SUB26433
Created by admin on Fri Dec 15 15:57:41 GMT 2023 , Edited by admin on Fri Dec 15 15:57:41 GMT 2023
PRIMARY
MERCK INDEX
m7397
Created by admin on Fri Dec 15 15:57:41 GMT 2023 , Edited by admin on Fri Dec 15 15:57:41 GMT 2023
PRIMARY Merck Index
CAS
555-30-6
Created by admin on Fri Dec 15 15:57:41 GMT 2023 , Edited by admin on Fri Dec 15 15:57:41 GMT 2023
PRIMARY
FDA UNII
M4R0H12F6M
Created by admin on Fri Dec 15 15:57:41 GMT 2023 , Edited by admin on Fri Dec 15 15:57:41 GMT 2023
PRIMARY
DRUG BANK
DB00968
Created by admin on Fri Dec 15 15:57:41 GMT 2023 , Edited by admin on Fri Dec 15 15:57:41 GMT 2023
PRIMARY
NSC
169916
Created by admin on Fri Dec 15 15:57:41 GMT 2023 , Edited by admin on Fri Dec 15 15:57:41 GMT 2023
PRIMARY
WIKIPEDIA
METHYLDOPA
Created by admin on Fri Dec 15 15:57:41 GMT 2023 , Edited by admin on Fri Dec 15 15:57:41 GMT 2023
PRIMARY
CHEBI
61058
Created by admin on Fri Dec 15 15:57:41 GMT 2023 , Edited by admin on Fri Dec 15 15:57:41 GMT 2023
PRIMARY
Related Record Type Details
SOLVATE->ANHYDROUS
TARGET -> INHIBITOR
SALT/SOLVATE -> PARENT
SUBSTANCE->BASIS OF STRENGTH
Related Record Type Details
METABOLITE -> PARENT
ACTIVE IN RATS
METABOLITE -> PARENT
URINE
PARENT -> METABOLITE
URINE
METABOLITE -> PARENT
URINE
METABOLITE -> PARENT
METABOLITE -> PARENT
URINE
METABOLITE -> PARENT
Approximately 70 percent of the drug which is absorbed is excreted in the urine as methyldopa and its mono-0-sulfate conjugate
MAJOR
PLASMA; URINE
Related Record Type Details
PARENT -> IMPURITY
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
Related Record Type Details
ACTIVE MOIETY