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

Details

Stereochemistry ABSOLUTE
Molecular Formula C12H17NO4
Molecular Weight 239.2677
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of METHYLDOPATE

SMILES

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

InChI

InChIKey=SVEBYYWCXTVYCR-LBPRGKRZSA-N
InChI=1S/C12H17NO4/c1-3-17-11(16)12(2,13)7-8-4-5-9(14)10(15)6-8/h4-6,14-15H,3,7,13H2,1-2H3/t12-/m0/s1

HIDE SMILES / InChI

Molecular Formula C12H17NO4
Molecular Weight 239.2677
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

-2.21961601E11
Primary
ALDOMET

Approved Use

INDICATION AND USAGE: Hypertension.

Launch Date

-2.21961601E11
Primary
ALDOMET

Approved Use

INDICATION AND USAGE: Hypertension.

Launch Date

-2.21961601E11
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

8.1233281E11
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
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
Dementia induced by methyldopa with haloperidol.
1976 May 27
Cardiac hypertrophy and antihypertensive therapy.
1977 Sep
Development and trends in the drug treatment of essential hypertension.
1992 Dec
Autoantibodies associated with lupus induced by diverse drugs target a similar epitope in the (H2A-H2B)-DNA complex.
1992 Jul
Centrally acting imidazoline I1-receptor agonists: do they have a place in the management of hypertension?
2001
Methyldopa versus no drug treatment in the management of mild pre-eclampsia.
2002 Apr
Immune-mediated drug-induced liver disease.
2002 Aug
Liddle syndrome in a newborn infant.
2002 Aug
Effects of six anti-hypertensive medications on cognitive performance.
2002 Aug
[Primary aldosteronism and pregnancy: report of 2 cases].
2002 Dec
Calcium channel blocker, nimodipine, for the treatment of bipolar disorder during pregnancy.
2002 Dec
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
Detection of alpha-methyldopa on thin-layer plates using pi-acceptors in 1,4-dioxane.
2002 Jul-Aug
The treatment of hypertension in pregnancy.
2002 May
The effect of antihypertensive drugs on the fetus.
2002 May
The effects of dopamine synthesis inhibitors and dopamine antagonists on regeneration in the hydra Hydra attenuata.
2002 May-Jun
Analysis of L-dopa in human serum.
2002 Nov
Pathophysiology and treatment of hot flashes.
2002 Nov
Nephropathic cystinosis associated with cardiomyopathy: a 27-year clinical follow-up.
2002 Nov 9
Spectrophotometric investigations of the assay of physiologically active catecholamines in pharmaceutical formulations.
2002 Nov-Dec
Oral beta-blockers for mild to moderate hypertension during pregnancy.
2003
Determination of antioxidant activity of some drugs using high-pressure liquid chromatography.
2003
Comparative single- and multiple-dose pharmacokinetics of levodopa and 3-O-methyldopa following a new dual-release and a conventional slow-release formulation of levodopa and benserazide in healthy volunteers.
2003
Shifting trends in the pharmacologic treatment of hypertension in a Nigerian tertiary hospital: a real-world evaluation of the efficacy, safety, rationality and pharmaco-economics of old and newer antihypertensive drugs.
2003 Apr
Antihypertensive drug-associated sexual dysfunction: a prescription analysis-based study.
2003 Apr-May
Angiotensin II-receptor-antagonists: further evidence of fetotoxicity but not teratogenicity.
2003 Aug
Binding site of salsolinol: its properties in different regions of the brain and the pituitary gland of the rat.
2003 Jan
Pharmacokinetic profile of methyldopa in the brain of sinaortic-denervated rats.
2003 Jul
[Circadian blood pressure rhythm in preeclampsia as a predictor of maternal and obstetrical outcome].
2003 Jul-Aug
Antihypertensive efficacy of moxonidine in primary care: a 'real-life' study.
2003 Jul-Aug
Blood pressure response to out-patient drug treatment of hypertension in 1973-1993 at Korle-Bu Teaching Hospital, Accra, Ghana.
2003 Jun
Catechol-O-methyltransferase inhibition in erythrocytes and liver by BIA 3-202 (1-[3,4-dibydroxy-5-nitrophenyl]-2-phenyl-ethanone).
2003 Jun
Replacement of antipsychotic and antiepileptic medication by L-alpha-methyldopa in a woman with velocardiofacial syndrome.
2003 Mar
The aggressive treatment of hypertension.
2003 May 3
[Clinical observation on the efficacy enhancing and toxicity attenuating effect of nuzhen yangyin granule to the anti-parkinsonism therapy mainly with Medopa].
2003 Nov
Nocturnal sleep, daytime sleepiness, and quality of life in stable patients on hemodialysis.
2003 Nov 21
A survey of Canadian practitioners regarding the management of the hypertensive disorders of pregnancy.
2004
Preeclampsia with abnormal liver function tests is associated with cholestasis in a subgroup of cases.
2004
[Methyldopa in therapy of hypertension in pregnant women].
2004 Feb
Chronic ethanol administration attenuates imidazoline I1 receptor- or alpha 2-adrenoceptor-mediated reductions in blood pressure and hemodynamic variability in hypertensive rats.
2004 Feb 6
[Dementia induced by cardiokinetic and anti-hypertensive drugs].
2004 Jan
Liquid chromatography-tandem mass spectrometry method for the determination of tranexamic acid in human plasma.
2004 Jun 15
[Centrally-acting antihypertensive drugs].
2004 Mar
[Hypertension in pregnancy].
2004 Mar
Differential modulation by estrogen of alpha2-adrenergic and I1-imidazoline receptor-mediated hypotension in female rats.
2004 Oct
Treating high blood pressure in Africans with type 2 diabetes.
2004 Winter
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 15:49:16 UTC 2023
Edited
by admin
on Fri Dec 15 15:49:16 UTC 2023
Record UNII
2579Z4P04J
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
METHYLDOPATE
VANDF   WHO-DD  
Common Name English
METHYLDOPATE [VANDF]
Common Name English
L-TYROSINE, 3-HYDROXY-.ALPHA.-METHYL-, ETHYL ESTER
Common Name English
L-3-(3,4-DIHYDROXYPHENYL)-2-METHYLALANINE ETHYL ESTER
Common Name English
Methyldopate [WHO-DD]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C29709
Created by admin on Fri Dec 15 15:49:16 UTC 2023 , Edited by admin on Fri Dec 15 15:49:16 UTC 2023
Code System Code Type Description
EPA CompTox
DTXSID8048523
Created by admin on Fri Dec 15 15:49:16 UTC 2023 , Edited by admin on Fri Dec 15 15:49:16 UTC 2023
PRIMARY
ChEMBL
CHEMBL1201233
Created by admin on Fri Dec 15 15:49:16 UTC 2023 , Edited by admin on Fri Dec 15 15:49:16 UTC 2023
PRIMARY
RXCUI
6877
Created by admin on Fri Dec 15 15:49:16 UTC 2023 , Edited by admin on Fri Dec 15 15:49:16 UTC 2023
PRIMARY RxNorm
CAS
2544-09-4
Created by admin on Fri Dec 15 15:49:16 UTC 2023 , Edited by admin on Fri Dec 15 15:49:16 UTC 2023
SUPERSEDED
DRUG CENTRAL
4218
Created by admin on Fri Dec 15 15:49:16 UTC 2023 , Edited by admin on Fri Dec 15 15:49:16 UTC 2023
PRIMARY
FDA UNII
2579Z4P04J
Created by admin on Fri Dec 15 15:49:16 UTC 2023 , Edited by admin on Fri Dec 15 15:49:16 UTC 2023
PRIMARY
NCI_THESAURUS
C75041
Created by admin on Fri Dec 15 15:49:16 UTC 2023 , Edited by admin on Fri Dec 15 15:49:16 UTC 2023
PRIMARY
CAS
6014-30-8
Created by admin on Fri Dec 15 15:49:16 UTC 2023 , Edited by admin on Fri Dec 15 15:49:16 UTC 2023
PRIMARY
PUBCHEM
17277
Created by admin on Fri Dec 15 15:49:16 UTC 2023 , Edited by admin on Fri Dec 15 15:49:16 UTC 2023
PRIMARY
EVMPD
SUB08867MIG
Created by admin on Fri Dec 15 15:49:16 UTC 2023 , Edited by admin on Fri Dec 15 15:49:16 UTC 2023
PRIMARY
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