METHYLDOPATE

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 Search

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

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 8297	60.0 µM [IC50]
Adrenergic receptor alpha 64 Target ID: CHEMBL2095203 Sources: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=f5f25053-a9f3-48b9-a412-078f5ee942fd&type=display	Agonist 2678
Adrenergic receptor alpha 64 Target ID: CHEMBL2094111 Sources: https://www.drugs.com/pro/methyldopa.html	Agonist 2678

Conditions

Condition	Modality	Highest Phase	Product
Hypertension 567 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/13400s086lbl.pdf	Primary	Approved 8429	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 8429	ALDOMET Approved Use INDICATION AND USAGE: Hypertension. Launch Date 1962
Hypertension 567 Sources: https://www.drugs.com/pro/methyldopate.html	Primary	Approved 8429	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
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
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

T_1/2

Value	Dose	Co-administered	Analyte	Population
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
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

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 n = 1 Health Status: unknown Age Group: 19 Sex: M Population Size: 1 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 (mean) Recommended Dose: 2326 mg Route: oral Route: multiple Dose: 2326 mg Sources: https://pubmed.ncbi.nlm.nih.gov/20791420/	unhealthy, 36-68 n = 30 Health Status: unhealthy Condition: hypertension Age Group: 36-68 Sex: M+F Population Size: 30 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 n = 39 Health Status: unhealthy Condition: hypertension Sex: M+F Population Size: 39 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 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP450 65

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP450 65	substrate 3367 Sources: https://molpharm.aspetjournals.org/content/12/6/911 Page: abstract	likely

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 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
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
Aaron Chemicals	AR003S1W	http://www.aaronchem.com/555-30-6
Achemtek	0104-003502	http://www.achemtek.com/41372-08-1
Achemtek	0104-006717	http://www.achemtek.com/555-30-6
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
BLD Pharm	BD21439	http://www.bldpharm.com/products/555-30-6.html
BioCrick	BCC4676	http://www.biocrick.com/Methyldopa-BCC4676.html
BioSynth	W-105555	https://www.biosynth.com/en/products/chemical-intermediates/basic-intermediates/products/W-105555.html
BioSynth	Q-201392	https://www.biosynth.com/en/products/life-science/other-biochemicals/products/Q-201392.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
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
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	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
Sigma-Aldrich	1426002_USP	https://www.sigmaaldrich.com/catalog/product/usp/1426002?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
abcr GmbH	AB474211	http://www.abcr.com/shop/en/AB474211
eNovation Chemicals	K70850	https://www.enovationchem.com/ProductDetails.asp?ProductID=K70850
mcule	MCULE-8885874119	https://mcule.com/MCULE-8885874119/

PubMed

Title	Date	PubMed
[Use of alpha-methyldopa in the treatment of arterial hypertension].	1975 Aug 31	1227753
Dihydroergotamine: an effective treatment for postural hypotension due to antihypertensive drugs (ganglion-blocking agents excepted).	1976	135643
Dementia induced by methyldopa with haloperidol.	1976 May 27	1264138
Cardiac hypertrophy and antihypertensive therapy.	1977 Sep	145319
Development and trends in the drug treatment of essential hypertension.	1992 Dec	1363322
Autoantibodies associated with lupus induced by diverse drugs target a similar epitope in the (H2A-H2B)-DNA complex.	1992 Jul	1378852
Centrally acting imidazoline I1-receptor agonists: do they have a place in the management of hypertension?	2001	14728014
Methyldopa versus no drug treatment in the management of mild pre-eclampsia.	2002 Apr	12625668
Immune-mediated drug-induced liver disease.	2002 Aug	12362579
[Primary aldosteronism and pregnancy: report of 2 cases].	2002 Dec	12611241
Calcium channel blocker, nimodipine, for the treatment of bipolar disorder during pregnancy.	2002 Dec	12501088
Detection of alpha-methyldopa on thin-layer plates using pi-acceptors in 1,4-dioxane.	2002 Jul-Aug	12426821
Analysis of L-dopa in human serum.	2002 Nov	12449374
Pathophysiology and treatment of hot flashes.	2002 Nov	12440557
Nephropathic cystinosis associated with cardiomyopathy: a 27-year clinical follow-up.	2002 Nov 9	12425721
Spectrophotometric investigations of the assay of physiologically active catecholamines in pharmaceutical formulations.	2002 Nov-Dec	12477190
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
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	12464717
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	12714973
Antihypertensive drug-associated sexual dysfunction: a prescription analysis-based study.	2003 Apr-May	12733473
Angiotensin II-receptor-antagonists: further evidence of fetotoxicity but not teratogenicity.	2003 Aug	14632309
Methyldopa supplement for resistant essential hypertension: a prospective randomized placebo control crossover study.	2003 Dec	14971524
Binding site of salsolinol: its properties in different regions of the brain and the pituitary gland of the rat.	2003 Jan	12441164
Pharmacokinetic profile of methyldopa in the brain of sinaortic-denervated rats.	2003 Jul	12770516
[Circadian blood pressure rhythm in preeclampsia as a predictor of maternal and obstetrical outcome].	2003 Jul-Aug	14528415
Antihypertensive efficacy of moxonidine in primary care: a 'real-life' study.	2003 Jul-Aug	12918886
Blood pressure response to out-patient drug treatment of hypertension in 1973-1993 at Korle-Bu Teaching Hospital, Accra, Ghana.	2003 Jun	14529234
Catechol-O-methyltransferase inhibition in erythrocytes and liver by BIA 3-202 (1-[3,4-dibydroxy-5-nitrophenyl]-2-phenyl-ethanone).	2003 Jun	12787259
Replacement of antipsychotic and antiepileptic medication by L-alpha-methyldopa in a woman with velocardiofacial syndrome.	2003 Mar	12598825
The aggressive treatment of hypertension.	2003 May 3	12737860
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
Nocturnal sleep, daytime sleepiness, and quality of life in stable patients on hemodialysis.	2003 Nov 21	14633280
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

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:49:16 GMT 2023` Edited by `admin` on `Fri Dec 15 15:49:16 GMT 2023`
Record UNII	2579Z4P04J
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

METHYLDOPATE

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