methyldopa Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
dopamine receptor agonists, dopamine derivatives, used as antiparkinsonism/prolactin inhibitors	1762	555-30-6

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: methyldopa (levorotatory) methyldopa aldochlor aldomine alphamethyldopa lederdopa (-)-alpha-Methyl-3,4-dihydroxyphenylalanine	An alpha-2 adrenergic agonist that has both central and peripheral nervous system effects. Its primary clinical use is as an antihypertensive agent. Molecular weight: 211.22 Formula: C10H13NO4 CLOGP: -2.26 LIPINSKI: 0 HAC: 5 HDO: 4 TPSA: 103.78 ALOGS: -1.97 ROTB: 3 Status: OFP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

methyldopa (levorotatory)
methyldopa
aldochlor
aldomine
alphamethyldopa
lederdopa
(-)-alpha-Methyl-3,4-dihydroxyphenylalanine

An alpha-2 adrenergic agonist that has both central and peripheral nervous system effects. Its primary clinical use is as an antihypertensive agent.

Molecular weight: 211.22
Formula: C10H13NO4
CLOGP: -2.26
LIPINSKI: 0
HAC: 5
HDO: 4
TPSA: 103.78
ALOGS: -1.97
ROTB: 3

Status: OFP

Legend:
OFP - off patent
OFM - off market
ONP - on patent

Drug dosage:

Dose	Unit	Route
1	g	O
1	g	P

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	3	Benet LZ, Broccatelli F, Oprea TI
S (Water solubility)	10 mg/mL	Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine)	40 %	Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose)	157.66 µM/kg/day	Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability)	42 %	Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution)	0.69 L/kg	Lombardo F, Berellini G, Obach RS
CL (Clearance)	3.50 mL/min/kg	Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma)	0.85 %	Lombardo F, Berellini G, Obach RS
t_half (Half-life)	5.90 hours	Lombardo F, Berellini G, Obach RS

Approvals:

Date	Agency	Company	Orphan
Dec. 20, 1962	FDA

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Premature delivery	1064.60	26.52	298	6432	21771	46657561
Exposure during pregnancy	991.10	26.52	420	6310	107792	46571540
Maternal exposure during pregnancy	958.70	26.52	404	6326	102145	46577187
Foetal exposure during pregnancy	611.72	26.52	211	6519	30536	46648796
Premature baby	532.07	26.52	167	6563	17945	46661387
Pre-eclampsia	402.66	26.52	112	6618	7882	46671450
Low birth weight baby	277.49	26.52	77	6653	5357	46673975
Caesarean section	261.45	26.52	96	6634	16507	46662825
Premature labour	210.42	26.52	74	6656	11225	46668107
Oligohydramnios	196.69	26.52	59	6671	5406	46673926
Foetal growth restriction	186.01	26.52	59	6671	6508	46672824
Patent ductus arteriosus	144.61	26.52	43	6687	3819	46675513
Live birth	141.60	26.52	54	6676	10276	46669056
Atrial septal defect	127.57	26.52	44	6686	6288	46673044
HELLP syndrome	121.88	26.52	28	6702	898	46678434
Gestational diabetes	107.12	26.52	40	6690	7179	46672153
Polyhydramnios	95.92	26.52	27	6703	1972	46677360
Conjoined twins	91.80	26.52	18	6712	263	46679069
Ventricular septal defect	88.95	26.52	30	6700	4004	46675328
Small for dates baby	87.96	26.52	29	6701	3608	46675724
Gestational hypertension	85.06	26.52	25	6705	2130	46677202
Intestinal malrotation	82.06	26.52	17	6713	332	46679000
Neonatal respiratory distress syndrome	72.69	26.52	23	6707	2510	46676822
Hypertension	69.50	26.52	111	6619	196245	46483087
Premature rupture of membranes	67.41	26.52	25	6705	4398	46674934
Congenital bladder anomaly	67.09	26.52	13	6717	178	46679154
Congenital choroid plexus cyst	67.07	26.52	14	6716	284	46679048
Ureteric stenosis	66.98	26.52	16	6714	609	46678723
Proteinuria	66.90	26.52	37	6693	16516	46662816
Urachal abnormality	66.82	26.52	13	6717	182	46679150
Persistent cloaca	65.67	26.52	13	6717	200	46679132
Placental insufficiency	63.96	26.52	18	6712	1313	46678019
Normal newborn	63.39	26.52	26	6704	5975	46673357
Premature separation of placenta	55.06	26.52	17	6713	1711	46677621
Pregnancy	54.69	26.52	39	6691	27098	46652234
Hypoglycaemia neonatal	51.11	26.52	14	6716	924	46678408
Foetal death	50.99	26.52	25	6705	8718	46670614
Ovarian cyst	42.37	26.52	26	6704	14061	46665271
Stillbirth	42.21	26.52	20	6710	6471	46672861
Toxoplasmosis	41.42	26.52	13	6717	1381	46677951
Microcephaly	40.90	26.52	11	6719	677	46678655
Limb malformation	40.21	26.52	10	6720	451	46678881
Foetal distress syndrome	38.55	26.52	12	6718	1241	46678091
Foetal exposure timing unspecified	37.04	26.52	8	6722	192	46679140
Breech presentation	35.61	26.52	11	6719	1109	46678223
Hypertonia neonatal	35.49	26.52	8	6722	235	46679097
Adiposis dolorosa	34.50	26.52	8	6722	267	46679065
Blood pressure inadequately controlled	33.08	26.52	15	6715	4391	46674941
Neonatal respiratory failure	31.84	26.52	7	6723	183	46679149
Delayed fontanelle closure	31.82	26.52	5	6725	17	46679315
Congenital hydronephrosis	31.46	26.52	8	6722	395	46678937
Selective eating disorder	30.82	26.52	11	6719	1734	46677598
Foetal heart rate deceleration abnormality	30.41	26.52	8	6722	452	46678880
Fatigue	29.20	26.52	27	6703	608670	46070662
Respiratory disorder neonatal	29.02	26.52	9	6721	919	46678413
Bicuspid aortic valve	28.92	26.52	6	6724	118	46679214
Blood pressure diastolic increased	28.74	26.52	15	6715	5959	46673373
Diaphragmatic paralysis	28.52	26.52	8	6722	576	46678756
Renal failure neonatal	28.37	26.52	6	6724	130	46679202
Cervical incompetence	28.01	26.52	8	6722	615	46678717
Blood pressure diastolic abnormal	28.00	26.52	15	6715	6279	46673053
Blood pressure increased	27.41	26.52	58	6672	126608	46552724
Blood pressure systolic abnormal	26.96	26.52	14	6716	5503	46673829

FDA Adverse Event Reporting System (Male)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Foetal exposure during pregnancy	1049.70	49.15	302	2673	36569	29912934
Premature baby	766.99	49.15	200	2775	16491	29933012
Low birth weight baby	475.75	49.15	112	2863	5964	29943539
Atrial septal defect	403.57	49.15	100	2875	6601	29942902
Small for dates baby	249.96	49.15	59	2916	3149	29946354
Foetal growth restriction	212.98	49.15	53	2922	3532	29945971
Patent ductus arteriosus	204.13	49.15	50	2925	3119	29946384
Hypospadias	171.15	49.15	42	2933	2637	29946866
Large for dates baby	163.46	49.15	33	2942	837	29948666
Respiratory disorder neonatal	158.87	49.15	34	2941	1154	29948349
Infantile apnoea	156.83	49.15	32	2943	857	29948646
Diabetic foetopathy	136.55	49.15	23	2952	203	29949300
Hypoglycaemia neonatal	117.39	49.15	28	2947	1555	29947948
Selective eating disorder	110.56	49.15	27	2948	1657	29947846
Ventricular septal defect	108.46	49.15	31	2944	3498	29946005
Neonatal respiratory failure	102.04	49.15	19	2956	310	29949193
Neonatal respiratory distress syndrome	100.19	49.15	30	2945	3982	29945521
Foetal disorder	94.61	49.15	20	2955	638	29948865
Bradycardia neonatal	93.44	49.15	21	2954	895	29948608
Caesarean section	89.78	49.15	24	2951	2113	29947390
Maternal drugs affecting foetus	85.67	49.15	27	2948	4246	29945257
Maternal exposure during pregnancy	84.06	49.15	26	2949	3845	29945658
Pulmonary hypoplasia	72.97	49.15	15	2960	416	29949087
Hydrops foetalis	67.44	49.15	13	2962	257	29949246
Cryptorchism	66.51	49.15	18	2957	1659	29947844
Hypotonia neonatal	65.00	49.15	16	2959	1013	29948490
Pulmonary valve stenosis congenital	61.68	49.15	11	2964	139	29949364
Exposure during pregnancy	58.58	49.15	25	2950	9236	29940267
Neutropenia neonatal	58.43	49.15	13	2962	528	29948975
Congenital hydronephrosis	55.53	49.15	13	2962	664	29948839
Apgar score low	52.07	49.15	13	2962	872	29948631
Congenital cystic lung	50.56	49.15	10	2965	227	29949276

Pharmacologic Action:

Source	Code	Description
ATC	C02AB01	CARDIOVASCULAR SYSTEM ANTIHYPERTENSIVES ANTIADRENERGIC AGENTS, CENTRALLY ACTING Methyldopa
ATC	C02LB01	CARDIOVASCULAR SYSTEM ANTIHYPERTENSIVES ANTIHYPERTENSIVES AND DIURETICS IN COMBINATION Methyldopa and diuretics in combination
MeSH PA	D018663	Adrenergic Agents
MeSH PA	D000322	Adrenergic Agonists
MeSH PA	D058647	Adrenergic alpha-2 Receptor Agonists
MeSH PA	D000316	Adrenergic alpha-Agonists
MeSH PA	D000959	Antihypertensive Agents
MeSH PA	D002317	Cardiovascular Agents
MeSH PA	D018377	Neurotransmitter Agents
MeSH PA	D018373	Peripheral Nervous System Agents
MeSH PA	D013565	Sympatholytics
CHEBI has role	CHEBI:35569	alpha-adrenergic receptor agonist
CHEBI has role	CHEBI:35674	antihypertensive
CHEBI has role	CHEBI:49110	peripheral nervous system agent
CHEBI has role	CHEBI:59174	haptens
CHEBI has role	CHEBI:66991	sympatholytics

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Hypertensive disorder	indication	38341003	DOID:10763
Anuria	contraindication	2472002	DOID:2983
Hypercholesterolemia	contraindication	13644009
Cirrhosis of liver	contraindication	19943007	DOID:5082
Secondary angle-closure glaucoma	contraindication	21571006
Hypovolemia	contraindication	28560003
Parkinsonism	contraindication	32798002
Dehydration	contraindication	34095006
Depressive disorder	contraindication	35489007
Hyperuricemia	contraindication	35885006	DOID:1920
Acute hepatitis	contraindication	37871000
Hypokalemia	contraindication	43339004
Chronic heart failure	contraindication	48447003
Systemic lupus erythematosus	contraindication	55464009	DOID:9074
Sympathectomy	contraindication	57071006
Acute nephropathy	contraindication	58574008
Hepatic failure	contraindication	59927004
Hypercalcemia	contraindication	66931009	DOID:12678
Hyperparathyroidism	contraindication	66999008	DOID:13543
Hypochloremic alkalosis	contraindication	70134007
Hepatic coma	contraindication	72836002	DOID:12550
Diabetes mellitus	contraindication	73211009	DOID:9351
Oliguria	contraindication	83128009
Hyponatremia	contraindication	89627008
Gout	contraindication	90560007	DOID:13189
Kidney disease	contraindication	90708001	DOID:557
Hypomagnesemia	contraindication	190855004
Angina pectoris	contraindication	194828000
Acute pancreatitis	contraindication	197456007	DOID:2913
Disease of liver	contraindication	235856003	DOID:409
Edema	contraindication	267038008
Anemia	contraindication	271737000	DOID:2355
Neonatal hyperbilirubinemia	contraindication	281610001
Pheochromocytoma	contraindication	302835009
Hypertriglyceridemia	contraindication	302870006
Autoimmune hemolytic anemia	contraindication	413603009	DOID:718
Porphyria	contraindication	418470004
Azotemia	contraindication	445009001
Severe Cerebrovascular Disease	contraindication

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	2.51	acidic
pKa2	8.98	acidic
pKa3	13.39	acidic
pKa4	10.04	Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
Alpha-2A adrenergic receptor	GPCR	P08913	ADA2A_HUMAN	AGONIST			WOMBAT-PK	CHEMBL
Epidermal growth factor receptor	Kinase	P00533	EGFR_HUMAN		IC50	5.28	DRUG MATRIX
Tyrosine-protein kinase Fyn	Kinase	P06241	FYN_HUMAN		IC50	5.29	DRUG MATRIX
Aromatic-L-amino-acid decarboxylase	Enzyme	P20711	DDC_HUMAN				WOMBAT-PK
Lysine-specific demethylase 4E	Enzyme	B2RXH2	KDM4E_HUMAN		IC50	5.52	CHEMBL
Arachidonate 15-lipoxygenase	Enzyme		LOX15_RABIT		IC50	5.67	DRUG MATRIX

External reference:

ID	Source
4017896	VUID
N0000146248	NUI
D08205	KEGG_DRUG
41372-08-1	SECONDARY_CAS_RN
4017896	VANDF
C0025741	UMLSCUI
CHEBI:61058	CHEBI
CHEMBL459	ChEMBL_ID
DB00968	DRUGBANK_ID
CHEMBL718	ChEMBL_ID
4138	PUBCHEM_CID
D008750	MESH_DESCRIPTOR_UI
56LH93261Y	UNII
6876	RXNORM
1035	MMSL
5088	MMSL
d00133	MMSL
000646	NDDF
373542000	SNOMEDCT_US
84078002	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Methyldopa	HUMAN PRESCRIPTION DRUG LABEL	1	16729-029	TABLET, FILM COATED	125 mg	ORAL	ANDA	23 sections
Methyldopa	HUMAN PRESCRIPTION DRUG LABEL	1	16729-030	TABLET, FILM COATED	250 mg	ORAL	ANDA	23 sections
Methyldopa	HUMAN PRESCRIPTION DRUG LABEL	1	16729-031	TABLET, FILM COATED	500 mg	ORAL	ANDA	23 sections
Methyldopa	HUMAN PRESCRIPTION DRUG LABEL	1	21695-879	TABLET, FILM COATED	250 mg	ORAL	ANDA	23 sections
Methyldopa	HUMAN PRESCRIPTION DRUG LABEL	1	21695-880	TABLET, FILM COATED	500 mg	ORAL	ANDA	23 sections
Methyldopa	HUMAN PRESCRIPTION DRUG LABEL	1	42254-351	TABLET, FILM COATED	250 mg	ORAL	ANDA	23 sections
Methyldopa	HUMAN PRESCRIPTION DRUG LABEL	1	54868-0050	TABLET, FILM COATED	250 mg	ORAL	ANDA	23 sections
Methyldopa	HUMAN PRESCRIPTION DRUG LABEL	1	54868-1328	TABLET, FILM COATED	500 mg	ORAL	ANDA	23 sections
Methyldopa	HUMAN PRESCRIPTION DRUG LABEL	1	68151-2791	TABLET, FILM COATED	250 mg	ORAL	ANDA	23 sections