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

Stem definitionDrug idCAS RN
dopamine receptor agonists, dopamine derivatives, used as antiparkinsonism/prolactin inhibitors 1762 555-30-6

Description:

MoleculeDescription

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:

DoseUnitRoute
1 g O
1 g P

ADMET properties:

PropertyValueReference
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 ┬ÁM/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:

DateAgencyCompanyOrphan
Dec. 20, 1962 FDA

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients 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 termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients 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:

SourceCodeDescription
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)

DiseaseRelationSNOMED_IDDOID
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 levelDissociation constantType (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:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Alpha-2A adrenergic receptor GPCR AGONIST WOMBAT-PK CHEMBL
Epidermal growth factor receptor Kinase IC50 5.28 DRUG MATRIX
Tyrosine-protein kinase Fyn Kinase IC50 5.29 DRUG MATRIX
Aromatic-L-amino-acid decarboxylase Enzyme WOMBAT-PK
Lysine-specific demethylase 4E Enzyme IC50 5.52 CHEMBL
Arachidonate 15-lipoxygenase Enzyme IC50 5.67 DRUG MATRIX

External reference:

IDSource
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:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
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