METHYLDOPA

Details

Stereochemistry	ABSOLUTE
Molecular Formula	2C10H13NO4.3H2O
Molecular Weight	476.4749
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O.O.O.C[C@](N)(CC1=CC=C(O)C(O)=C1)C(O)=O.C[C@](N)(CC2=CC=C(O)C(O)=C2)C(O)=O

InChI

InChIKey=YKFCISHFRZHKHY-NGQGLHOPSA-N

InChI=1S/2C10H13NO4.3H2O/c2*1-10(11,9(14)15)5-6-2-3-7(12)8(13)4-6;;;/h2*2-4,12-13H,5,11H2,1H3,(H,14,15);3*1H2/t2*10-;;;/m00.../s1

HIDE SMILES / InChI

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/13400s086lbl.pdfhttps://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=f5f25053-a9f3-48b9-a412-078f5ee942fd&type=display
Curator's Comment: Description was created based on several sources, including

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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
DOPA decarboxylase 15 Target ID: CHEMBL1843 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7136732	Inhibitor 8504	60.0 µM [IC50]
Adrenergic receptor alpha 65 Target ID: CHEMBL2095203 Sources: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=f5f25053-a9f3-48b9-a412-078f5ee942fd&type=display	Agonist 2752
Adrenergic receptor alpha 65 Target ID: CHEMBL2094111 Sources: https://www.drugs.com/pro/methyldopa.html	Agonist 2752

Conditions

Condition	Modality	Highest Phase	Product
Hypertension 575 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/13400s086lbl.pdf	Primary	Approved 8583	ALDOMET Approved Use INDICATION AND USAGE: Hypertension. Launch Date 1962
Preeclampsia 85 Sources: https://clinicaltrials.gov/ct2/show/NCT00117546	Primary	Phase IV 63	ALDOMET Approved Use INDICATION AND USAGE: Hypertension. Launch Date 1962
Type 1 diabetes in DQ8 positive patients with residual beta cell function 4 Sources: http://reference.medscape.com/drug/aldomet-methyldopa-342385	Primary	Approved 8583	ALDOMET Approved Use INDICATION AND USAGE: Hypertension. Launch Date 1962
Hypertension 575 Sources: https://www.drugs.com/pro/methyldopate.html	Primary	Approved 8583	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

C_max

Value	Dose	Co-administered	Analyte	Population
771.3 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21125810	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

Value	Dose	Co-administered	Analyte	Population
5352.9 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21125810	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
4.54 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7047042	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
12.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21125810	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
1.28 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7047042	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

F_unbound

Value	Dose	Co-administered	Analyte	Population
85% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7047042	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

Dose	Population	Adverse events
2.5 g single, oral Dose: 2.5 g Route: oral Route: single Dose: 2.5 g Sources: https://pubmed.ncbi.nlm.nih.gov/7175995/	unknown, 19 Health Status: unknown Age Group: 19 Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/7175995/	Other AEs: Coma... Other AEs: Coma (grade 1) Sources: https://pubmed.ncbi.nlm.nih.gov/7175995/
2326 mg multiple, oral Recommended Dose: 2326 mg Route: oral Route: multiple Dose: 2326 mg Sources: https://pubmed.ncbi.nlm.nih.gov/20791420/	unhealthy, 36-68 Health Status: unhealthy Age Group: 36-68 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/20791420/	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: https://pubmed.ncbi.nlm.nih.gov/20791420/
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: https://pubmed.ncbi.nlm.nih.gov/14269222/	unhealthy Health Status: unhealthy Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/14269222/	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: https://pubmed.ncbi.nlm.nih.gov/14269222/

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
			inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP450 59

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP450 59	substrate 4014 Sources: https://molpharm.aspetjournals.org/content/12/6/911 Page: abstract	likely

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.scirp.org/pdf/JBiSE_2017112915210255.pdf Page: 10.0

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY560228	https://www.001chemical.com/chem/555-30-6
3B Scientific (Wuhan) Corp	3B2-0576	http://www.3bsc.com/index/pro_info.php?id=19932
AA Blocks	AA003RA4	http://www.aablocks.com/goods/Goods/detail?id=AA003RA4
Aaron Chemicals	AR003S1W	http://www.aaronchem.com/555-30-6
abcr GmbH	AB474211	http://www.abcr.com/shop/en/AB474211
Achemtek	0104-003502	http://www.achemtek.com/41372-08-1
Achemtek	0104-006717	http://www.achemtek.com/555-30-6
AHH Chemical co.,ltd	API-1546	http://www.ahhchemical.com/product/API-1546.html
AK Scientific, Inc. (AKSCI)	H155	http://www.aksci.com/item_detail.php?cat=H155
Alfa Chemistry	88620-56-8	https://www.alfa-chemistry.com/cas_88620-56-8.htm
Angene	AGN-PC-0SJ63Q	http://www.angenechemical.com/productshow/AGN-PC-0SJ63Q.html
Anward	ANW-43632	http://www.anward.com/pro_result/24839
ApexBio Technology	B1787	http://www.apexbt.com/methyldopa.html
Ark Pharm	AK114179	http://www.arkpharminc.com/products/555-30-6.html
Aurora Fine Chemicals LLC	A17.866.470	http://online.aurorafinechemicals.com/info?ID=A17.866.470
BioCrick	BCC4676	http://www.biocrick.com/Methyldopa-BCC4676.html
BioSynth	Q-201392	https://www.biosynth.com/en/products/life-science/other-biochemicals/products/Q-201392.html
BioSynth	W-105555	https://www.biosynth.com/en/products/chemical-intermediates/basic-intermediates/products/W-105555.html
BLD Pharm	BD21439	http://www.bldpharm.com/products/555-30-6.html
Chem Scene	CS-2172	http://www.chemscene.com/555-30-6.html
ChemMol	30101538	http://www.chemmol.com/chemmol/30101538.html
ChemMol	30101832	http://www.chemmol.com/chemmol/30101832.html
ChemMol	99105050	http://www.chemmol.com/chemmol/99105050.html
ChemMol	99161463	http://www.chemmol.com/chemmol/99161463.html
Chemspace	CSSB00000008965	https://chem-space.com/CSSB00000008965
Clearsynth	CS-O-30639	http://www.clearsynth.com/en/CSO30639.html
DAOGE BIOPHARMA	DG21-11796	https://www.daogechem.com/product/555-30-6.html
DC Chemicals	DC32910	http://www.dcchemicals.com//product_show-Dopamet.html
Enamine	Z1565440340	https://www.enaminestore.com/catalog/Z1565440340
eNovation Chemicals	K70850	https://www.enovationchem.com/ProductDetails.asp?ProductID=K70850
Hairui	HR122810	http://www.hairuichem.com/en/product/555-30-6.html
Hello Bio	HB1822	https://www.hellobio.com/l-alpha-methyldopa.html
Lab Network	LN00238713	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN00238713
mcule	MCULE-8885874119	https://mcule.com/MCULE-8885874119/
MedChem Express	HY-B0225	https://www.medchemexpress.com/l-_-_-_alpha_-methyldopa.html
Molcore	MC560228	https://www.molcore.com/product/555-30-6
Selleck Chemicals	S1642	http://www.selleckchem.com/products/Methyldopa(Aldomet).html
Sigma-Aldrich	1426002_USP	https://www.sigmaaldrich.com/catalog/product/usp/1426002?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	M1500000_SIAL	https://www.sigmaaldrich.com/catalog/product/sial/m1500000?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	Y0001083_SIAL	https://www.sigmaaldrich.com/catalog/product/sial/y0001083?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Smolecule	S535194	http://www.smolecule.com/products/s535194
Smolecule	S773215	https://www.smolecule.com/products/s773215
TCI (Tokyo Chemical Industry)	D1817	http://www.tcichemicals.com/eshop/en/us/commodity/D1817/index.html
THE BioTek	bt-275646	https://www.thebiotek.com/product/inhibitors/bt-275646
Tocris	584	https://www.tocris.com/products/l-a-methyldopa_0584
TripleBond	CM0081	http://www.triplebond-canada.com/prod/1430/
VladaChem	VL272043-1G	https://www.vladachem.com/product.php?products=555-30-6

PubMed

Title	Date	PubMed
Delayed hepatotoxicity from methyldopa.	1975 Dec	1204341
Acute reactive hepatitis in pregnancy induced by alpha-methyldopa.	1997 Oct	11770583
Centrally acting imidazoline I1-receptor agonists: do they have a place in the management of hypertension?	2001	14728014
Spectrophotometric determination of certain vicinal dihydroxybenzene derivatives in pharmaceutical preparations.	2001 Apr	11990572
Ddc and amd sequences resolve phylogenetic relationships of Drosophila.	2001 Aug	11476641
Effect of methyldopa on renal function in rats with L-NAME-induced hypertension in pregnancy.	2001 Aug	11474231
Drugs in pregnancy. Antihypertensives.	2001 Dec	11800527
Effect of phenobarbital and spironolactone treatment on the oxidative metabolism of antipyrine by rat liver microsomes.	2001 Jan-Feb	11785906
NHBPEP report on high blood pressure in pregnancy: a summary for family physicians.	2001 Jul 15	11476271
Pharmacokinetic and pharmacodynamic alterations of methyldopa in rats with aortic coarctation. A study using microdialysis.	2001 Nov	11712868
Juxtaglomerular cell tumor in pregnancy.	2001 Nov	11704214
Catechol-O-methyltransferase (COMT) genetic polymorphism in a Turkish population.	2001 Sep	11693181
Excretion of antihypertensive medication into human breast milk: a systematic review.	2002	12044345
[Primary aldosteronism and pregnancy: report of 2 cases].	2002 Dec	12611241
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	11854123
Preparation of (R) and (S) alpha methyldopa from a chiral hydantoin containing the alpha phenylethyl group.	2002 Feb-Mar	11835557
Brain catecholamine metabolism in catechol-O-methyltransferase (COMT)-deficient mice.	2002 Jan	11849292
Rapid-eye-movement sleep in jittery infants.	2002 Jan	11834345
Hypertension/preeclampsia.	2002 Jan-Feb	11875601
C4 deficiency state in antiphospholipid antibody-related recurrent preeclampsia evolving into systemic lupus erythematosus.	2002 Jul	12111090
Detection of alpha-methyldopa on thin-layer plates using pi-acceptors in 1,4-dioxane.	2002 Jul-Aug	12426821
Antihypertensive medication compliance in a Veterans Affairs Healthcare System.	2002 Jun	12022897
Sympatholytic therapy in primary hypertension: a user friendly role for the future.	2002 Mar	11986908
Quantification of methyldopa in human plasma by high-performance liquid chromatography-electrospray tandem mass spectrometry application to a bioequivalence study.	2002 Mar 5	11888062
The effect of antihypertensive drugs on the fetus.	2002 May	12082488
Nephropathic cystinosis associated with cardiomyopathy: a 27-year clinical follow-up.	2002 Nov 9	12425721
Oral beta-blockers for mild to moderate hypertension during pregnancy.	2003	12917933
Determination of antioxidant activity of some drugs using high-pressure liquid chromatography.	2003	12785121
Antihypertensive drug-associated sexual dysfunction: a prescription analysis-based study.	2003 Apr-May	12733473
Methyldopa supplement for resistant essential hypertension: a prospective randomized placebo control crossover study.	2003 Dec	14971524
Antihypertensive efficacy of moxonidine in primary care: a 'real-life' study.	2003 Jul-Aug	12918886
Catechol-O-methyltransferase inhibition in erythrocytes and liver by BIA 3-202 (1-[3,4-dibydroxy-5-nitrophenyl]-2-phenyl-ethanone).	2003 Jun	12787259
Physician gender and antihypertensive prescription pattern in primary care.	2003 Nov	14758963
[Clinical observation on the efficacy enhancing and toxicity attenuating effect of nuzhen yangyin granule to the anti-parkinsonism therapy mainly with Medopa].	2003 Nov	14666759
A survey of Canadian practitioners regarding the management of the hypertensive disorders of pregnancy.	2004	15117601
Preeclampsia with abnormal liver function tests is associated with cholestasis in a subgroup of cases.	2004	15117597
[Methyldopa in therapy of hypertension in pregnant women].	2004 Feb	15108591
Pheochromocytoma during pregnancy: laparoscopic and conventional surgical treatment of two cases.	2004 Feb	15031775
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	14757148
[Dementia induced by cardiokinetic and anti-hypertensive drugs].	2004 Jan	15011413
Oral enalapril-hydrochlorothiazide-methyldopa as first line treatment for severe hypertension in Nigerians.	2004 Jan	14959973
Treatment of menopause-associated vasomotor symptoms: position statement of The North American Menopause Society.	2004 Jan-Feb	14716179
Liquid chromatography-tandem mass spectrometry method for the determination of tranexamic acid in human plasma.	2004 Jun 15	15135101
[Centrally-acting antihypertensive drugs].	2004 Mar	15171442
[Hypertension in pregnancy].	2004 Mar	15171412
Mediated exodus of L-dopa from human epidermal Langerhans cells.	2004 Mar	15042441
Drug-induced liver injury.	2004 Mar 1	14986274
Differential modulation by estrogen of alpha2-adrenergic and I1-imidazoline receptor-mediated hypotension in female rats.	2004 Oct	15145918
Treating high blood pressure in Africans with type 2 diabetes.	2004 Winter	15002939
Inadequate control of blood pressure in Nigerians with diabetes.	2004 Winter	15002927

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

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

Name

Type

Language

METHYLDOPA

Official Name

English

METHYLDOPA SESQUIHYDRATE

Preferred Name

English

NSC-760080

Code

English

ALDORIL COMPONENT METHYLDOPA

Common Name

English

L-3-(3,4-DIHYDROXYPHENYL)-2-METHYLALANINE SESQUIHYDRATE

Common Name

English

ALPHA-METHYLDOPA

Common Name

English

DOPEGYT

Brand Name

English

METHYLDOPUM [WHO-IP LATIN]

Common Name

English

L-TYROSINE, 3-HYDROXY-.ALPHA.-METHYL-, SESQUIHYDRATE

Common Name

English

L-TYROSINE, 3-HYDROXY-.ALPHA.-METHYL-, HYDRATE (2:3)

Systematic Name

English

Methyldopa sesquihydrate [WHO-DD]

Common Name

English

PRESINOL

Brand Name

English

METHYLDOPA [USAN]

Common Name

English

METHYLDOPA [USP-RS]

Common Name

English

METHYLDOPA [USP MONOGRAPH]

Common Name

English

METHYLDOPA [ORANGE BOOK]

Common Name

English

METHYLDOPA [VANDF]

Common Name

English

MK-351

Code

English

METHYLDOPA SESQUIHYDRATE [MI]

Common Name

English

DOPAMET

Brand Name

English

METHYLDOPA SESQUIHYDRATE [MART.]

Common Name

English

METHYLDOPA [WHO-IP]

Common Name

English

METHYLDOPA HYDRATE

Systematic Name

English

METHYLDOPA [MART.]

Common Name

English

MEDOPREN

Brand Name

English

METHYLDOPA [EP MONOGRAPH]

Common Name

English

ALDOMET

Brand Name

English

METHYLDOPA HYDRATE [JAN]

Common Name

English

Classification Tree Code System Code

WHO-VATC

QC02AB01