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Showing drug card for Methyldopa (DB00968)

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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-04-16 16:48:11
Primary Accession Number DB00968
Secondary Accession Number
  • APRD01106
Name Methyldopa
Drug Type
  • Approved
  • Small Molecule
Description An alpha-2 adrenergic agonist that has both central and peripheral nervous system effects. Its primary clinical use is as an antihypertensive agent. [PubChem]
Synonyms
  1. AMD
  2. Alpha medopa
  3. Alphamethyldopa
  4. L-Methyl Dopa
  5. Methyldopa anhydrous
  6. Methyldopate
  7. Methyldopate HCL
  8. Mk. b51
Brand Names
  1. Aldoclor-150
  2. Aldoclor-250
  3. Aldomet
  4. Aldometil
  5. Aldomin
  6. Aldoril 15
  7. Aldoril 25
  8. Aldoril D30
  9. Aldoril D50
  10. Apo-Methyldopa
  11. Bayer 1440 L
  12. Baypresol
  13. Becanta
  14. Dopamet
  15. Dopamethyperpax
  16. Dopatec
  17. Dopegyt
  18. Grospisk
  19. Hyperpax
  20. Hypolag
  21. Medomet
  22. Medopa
  23. Medopal
  24. Medopren
  25. Methoplain
  26. Novomedopa
  27. Nu-Medopa
  28. Presinol
  29. Presolisin
  30. Sedometil
  31. Sembrina
Brand Mixtures
  1. Aldoril 15 Tab (Hydrochlorothiazide + Methyldopa)
  2. Aldoril 25 Tab (Hydrochlorothiazide + Methyldopa)
  3. Apo Methazide 15 (Hydrochlorothiazide + Methyldopa)
  4. Apo Methazide 25 (Hydrochlorothiazide + Methyldopa)
  5. Novo-Doparil 15 Tab (Hydrochlorothiazide + Methyldopa)
  6. Novo-Doparil 25 Tab (Hydrochlorothiazide + Methyldopa)
  7. Pms-Dopazide 15 Tab (Hydrochlorothiazide + Methyldopa)
  8. Pms-Dopazide-25 Tab (Hydrochlorothiazide + Methyldopa)
  9. Supres 150 Tab (Chlorothiazide + Methyldopa)
  10. Supres 250 Tab (Chlorothiazide + Methyldopa)
Chemical IUPAC Name (2S)-2-amino-3-(3,4-dihydroxyphenyl)-2-methylpropanoic acid
Chemical Formula C10H13NO4
Chemical Structure Structure
CAS Registry Number 555-30-6
InChI Identifier InChI=1/C10H13NO4/c1-10(11,9(14)15)5-6-2-3-7(12)8(13)4-6/h2-4,12-13H,5,11H2,1H3,(H,14,15)/t10-/m0/s1/f/h14H
InChI Key CJCSPKMFHVPWAR-RILOQBQWDC
KEGG Drug Not Available
KEGG Compound C07194 Link Image
PubChem Compound 38853 Link Image
PubChem Substance 9403 Link Image
ChEBI ID Not Available
PharmGKB ID PA450453 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 00426830 Link Image
RxList Link http://www.rxlist.com/cgi/generic2/methyl.htm Link Image
PDRhealth Link http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/ald1012.shtml Link Image
Wikipedia Link http://en.wikipedia.org/wiki/Methyldopa Link Image
FDA Label
Material Safety Data Sheet (MSDS)
Synthesis Reference Not Available
Average Molecular Weight 211.2145
Monoisotopic Molecular Weight 211.0845
State Solid
Melting Point 300 oC
Experimental Water Solubility 1000 mg/L Source: PhysProp
Predicted Water Solubility 2.26e+00 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity -1.7 Source: PhysProp
Predicted LogP -2.01 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -1.97 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point Not Available
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID Not Available
Isomeric SMILES C[C@](N)(CC1=CC(O)=C(O)C=C1)C(O)=O
Canonical SMILES CC(N)(CC1=CC(O)=C(O)C=C1)C(O)=O
Drug Category
  • Adrenergic alpha-Agonists
  • Antihypertensive Agents
  • Sympatholytics
ATC Codes
AHFS Codes
  • 24:08.16
Indication For use in the treatment of hypertension.
Pharmacology Methyldopa is an aromatic-amino-acid decarboxylase inhibitor in animals and in man. Only methyldopa, the L-isomer of alpha-methyldopa, has the ability to inhibit dopa decarboxylase and to deplete animal tissues of norepinephrine. In man the antihypertensive activity appears to be due solely to the L-isomer. About twice the dose of the racemate (DL-alpha-methyldopa) is required for equal antihypertensive effect. Methyldopa has no direct effect on cardiac function and usually does not reduce glomerular filtration rate, renal blood flow, or filtration fraction. Cardiac output usually is maintained without cardiac acceleration. In some patients the heart rate is slowed. Normal or elevated plasma renin activity may decrease in the course of methyldopa therapy. Methyldopa reduces both supine and standing blood pressure. Methyldopa usually produces highly effective lowering of the supine pressure with infrequent symptomatic postural hypotension. Exercise hypotension and diurnal blood pressure variations rarely occur.
Mechanism of Action Although the mechanism of action has yet to be conclusively demonstrated, the antihypertensive effect of methyldopa probably is due to its metabolism to alpha-methylnorepinephrine, which then lowers arterial pressure by stimulation of central inhibitory alpha-adrenergic receptors, false neurotransmission, and/or reduction of plasma renin activity. Methyldopa has been shown to cause a net reduction in the tissue concentration of serotonin, dopamine, norepinephrine, and epinephrine.
Absorption Absorption from the gastrointestinal tract is variable but averages approximately 50%.
Toxicity The oral LD50 of methyldopa is greater than 1.5 g/kg in both the mouse and the rat. Symptoms of overdose include bloating, constipation, diarrhea, dizziness, extreme drowsiness, gas, light-headedness, nausea, severely low blood pressure, slow heartbeat, vomiting, and weakness.
Protein Binding Low (less than 20%).
Biotransformation Hepatic, extensively metabolized. The known urinary metabolites are: a-methyldopa mono-0-sulfate; 3-0-methyl-a-methyldopa; 3,4-dihydroxyphenylacetone; a-methyldopamine; 3-0-methyl-a-methyldopamine and their conjugates.
Half Life The plasma half-life of methyldopa is 105 minutes.
Dosage Forms
Form Route
Tablet Oral
Patient Information Not Available
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Carteolol Possible hypertensive crisis
Dobutamine Increased arterial pressure
Dopamine Increased arterial pressure
Entacapone Entacapone increases the effect and toxicity of sympathomimetics
Ephedra Increased arterial pressure
Ephedrine Increased arterial pressure
Epinephrine Increased arterial pressure
Fenoterol Increased arterial pressure
Haloperidol Methyldopa increases haloperidol effect or risk of psychosis
Iron Iron decreases the absorption of dopa derivatives
Isoproterenol Increased arterial pressure
Levodopa Methyldopa increases the effect and toxicity of levodopa
Lithium Signs of increased lithium levels without increase with this combination
Mephentermine Increased arterial pressure
Metaraminol Increased arterial pressure
Methoxamine Increased arterial pressure
Nadolol Possible hypertensive crisis
Norepinephrine Increased arterial pressure
Orciprenaline Increased arterial pressure
Oxprenolol Possible hypertensive crisis
Penbutolol Possible hypertensive crisis
Phenylephrine Increased arterial pressure
Phenylpropanolamine Increased arterial pressure
Pindolol Possible hypertensive crisis
Pirbuterol Increased arterial pressure
Procaterol Increased arterial pressure
Propranolol Possible hypertensive crisis
Pseudoephedrine Increased arterial pressure
Salbutamol Increased arterial pressure
Sotalol Possible hypertensive crisis
Terbutaline Increased arterial pressure
Timolol Possible hypertensive crisis
Food Interactions
  • Avoid alcohol.
  • Avoid natural licorice.
  • Increase dietary intake of magnesium, folate, vitamin B6, B12, and/or consider taking a multivitamin.
  • May take Vitamin D.
  • No iron, zinc or fluoride within 2 hours of taking this medication.
  • Take without regard to meals.
Pathways Not Available
General References
  1. Wikipedia Link Image
  2. RxList Link Image
  3. PDRhealth Link Image
Organisms Affected
  • Humans and other mammals
Phase 1 Metabolizing Enzymes
  1. Catechol O-methyltransferase (COMT)
Targets
  1. Alpha-2A adrenergic receptor
Phase 1 Metabolizing Enzyme 1 [top]
Enzyme 1 Name Catechol O-methyltransferase (COMT)
Enzyme 1 Gene Name COMT
Enzyme 1 SwissProt ID P21964 Link Image
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 Protein Sequence >COMT ( catecol-O-methyl-transferase) 
MPEAPPLLLAAVLLGLVLLVVLLLLLRHWGWGLCLIGWNEFILQPIHNLLMGDTKEQRIL
NHVLQHAEPGNAQSVLEAIDTYCEQKEWAMNVGDKKGKIVDAVIQEHQPSVLLELGAYCG
YSAVRMARLLSPGARLITIEINPDCAAITQRMVDFAGVKDKVTLVVGASQDIIPQLKKKY
DVDTLDMVFLDHWKDRYLPDTLLLEECGLLRKGTVLLADNVICPGAPDFLAHVRGSSCFE
CTHYQSFLEYREVVDGLEKAIYKGPGSEAGP
Drug Target 1 [top]
Target 1 ID 318
Target 1 Name Alpha-2A adrenergic receptor
Target 1 Synonyms
  1. Alpha-2 adrenergic receptor subtype C10
  2. Alpha-2A adrenoceptor
  3. Alpha-2A adrenoreceptor
  4. Alpha-2AAR
Target 1 Gene Name ADRA2A
Target 1 Protein Sequence >Alpha-2A adrenergic receptor 
MGSLQPDAGNASWNGTEAPGGGARATPYSLQVTLTLVCLAGLLMLLTVFGNVLVIIAVFT
SRALKAPQNLFLVSLASADILVATLVIPFSLANEVMGYWYFGKAWCEIYLALDVLFCTSS
IVHLCAISLDRYWSITQAIEYNLKRTPRRIKAIIITVWVISAVISFPPLISIEKKGGGGG
PQPAEPRCEINDQKWYVISSCIGSFFAPCLIMILVYVRIYQIAKRRTRVPPSRRGPDAVA
APPGGTERRPNGLGPERSAGPGGAEAEPLPTQLNGAPGEPAPAGPRDTDALDLEESSSSD
HAERPPGPRRPERGPRGKGKARASQVKPGDSLPRRGPGATGIGTPAAGPGEERVGAAKAS
RWRGRQNREKRFTFVLAVVIGVFVVCWFPFFFTYTLTAVGCSVPRTLFKFFFWFGYCNSS
LNPVIYTIFNHDFRRAFKKILCRGDRKRIV
Target 1 Number of Residues 457
Target 1 Molecular Weight 48957
Target 1 Theoretical pI 10.20
Target 1 GO Classification
Function
signal transducer activity
receptor activity
transmembrane receptor activity
G-protein coupled receptor activity
rhodopsin-like receptor activity
amine receptor activity
adrenoceptor activity
alpha-adrenergic receptor activity
alpha2-adrenergic receptor activity
Process
cellular process
cell communication
signal transduction
cell surface receptor linked signal transduction
G-protein coupled receptor protein signaling pathway
Component
cell
membrane
intrinsic to membrane
integral to membrane
Target 1 General Function Involved in alpha2-adrenergic receptor activity
Target 1 Specific Function Alpha-2 adrenergic receptors mediate the catecholamine- induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • 34-59
  • 71-96
  • 107-129
  • 150-173
  • 193-217
  • 375-399
  • 407-430
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 178196 Link Image
Target 1 UniProtKB/Swiss-Prot ID P08913 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name ADA2A_HUMAN Link Image
Target 1 PDB ID 1HOF Link Image
Target 1 PDB File Show
Target 1 3D Structure
Target 1 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 1 Gene Sequence >1353 bp 
ATGGGCTCCCTGCAGCCGGACGCGGGCAACGCGAGCTGGAACGGGACCGAGGCGCCGGGG
GGCGGCGCCCGGGCCACCCCTTACTCCCTGCAGGTGACGCTGACGCTGGTGTGCCTGGCC
GGCCTGCTCATGCTGCTCACCGTGTTCGGCAACGTGCTCGTCATCATCGCCGTGTTCACG
AGCCGCGCGCTCAAGGCGCCCCAAAACCTCTTCCTGGTGTCTCTGGCCTCGGCCGACATC
CTGGTGGCCACGCTCGTCATCCCTTTCTCGCTGGCCAACGAGGTCATGGGCTACTGGTAC
TTCGGCAAGGCTTGGTGCGAGATCTACCTGGCGCTCGACGTGCTCTTCTGCACGTCGTCC
ATCGTGCACCTGTGCGCCATCAGCCTGGACCGCTACTGGTCCATCACACAGGCCATCGAG
TACAACCTGAAGCGCACGCCGCGCCGCATCAAGGCCATCATCATCACCGTGTGGGTCATC
TCGGCCGTCATCTCCTTCCCGCCGCTCATCTCCATCGAGAAGAAGGGCGGCGGCGGCGGC
CCGCAGCCGGCCGAGCCGCGCTGCGAGATCAACGACCAGAAGTGGTACGTCATCTCGTCG
TGCATCGGCTCCTTCTTCGCTCCCTGCCTCATCATGATCCTGGTCTACGTGCGCATCTAC
CAGATCGCCAAGCGTCGCACCCGCGTGCCACCCAGCCGCCGGGGTCCGGACGCCGTCGCC
GCGCCGCCGGGGGGCACCGAGCGCAGGCCCAACGGTCTGGGCCCCGAGCGCAGCGCGGGC
CCGGGGGGCGCAGAGGCCGAACCGCTGCCCACCCAGCTCAACGGCGCCCCTGGCGAGCCC
GCGCCGGCCGGGCCGCGCGACACCGACGCGCTGGACCTGGAGGAGAGCTCGTCTTCCGAC
CACGCCGAGCGGCCTCCAGGGCCCCGCAGACCCGAGCGCGGTCCCCGGGGCAAAGGCAAG
GCCCGAGCGAGCCAGGTGAAGCCGGGCGACAGCCTGCGCGGCGCGGGCCGGGGGCGACGG
GGATCGGGACGCCGGCTGCAGGGCCGGGGGAGGAGCGCGTCGGGGCTGCCAAGGCGTCGC
GCTGGCGCGGGCGGGCAGAACCGCGAGAAGCGCTTCACGTTCGTGCTGGCCGTGGTCATC
GGAGTGTTCGTGGTGTGCTGGTTCCCCTTCTTCTTCACCTACACGCTCACGGCCGTCGGG
TGCTCCGTGCCACGCACGCTCTTCAAATTCTTCTTCTGGTTCGGCTACTGCAACAGCTCG
TTGAACCCGGTCATCTACACCATCTTCAACCACGATTTCCGCCGCGCCTTCAAGAAGATC
CTCTGTCGGGGGGACAGGAAGCGGATCGTGTGA
Target 1 GenBank Gene ID
Target 1 GeneCard ID ADRA2A Link Image
Target 1 GenAtlas ID ADRA2A Link Image
Target 1 HGNC ID HGNC:281 Link Image
Target 1 Chromosome Location 10
Target 1 Locus 10q24-q26
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Chung DA, Zuiderweg ER, Fowler CB, Soyer OS, Mosberg HI, Neubig RR: NMR structure of the second intracellular loop of the alpha 2A adrenergic receptor: evidence for a novel cytoplasmic helix. Biochemistry. 2002 Mar 19;41(11):3596-604. [PubMed Link Image]
  2. Suryanarayana S, Daunt DA, Von Zastrow M, Kobilka BK: A point mutation in the seventh hydrophobic domain of the alpha 2 adrenergic receptor increases its affinity for a family of beta receptor antagonists. J Biol Chem. 1991 Aug 15;266(23):15488-92. [PubMed Link Image]
  3. Wang CD, Buck MA, Fraser CM: Site-directed mutagenesis of alpha 2A-adrenergic receptors: identification of amino acids involved in ligand binding and receptor activation by agonists. Mol Pharmacol. 1991 Aug;40(2):168-79. [PubMed Link Image]
  4. Chhajlani V, Rangel N, Uhlen S, Wikberg JE: Identification of an additional gene belonging to the alpha 2 adrenergic receptor family in the human genome by PCR. FEBS Lett. 1991 Mar 25;280(2):241-4. [PubMed Link Image]
  5. Guyer CA, Horstman DA, Wilson AL, Clark JD, Cragoe EJ Jr, Limbird LE: Cloning, sequencing, and expression of the gene encoding the porcine alpha 2-adrenergic receptor. Allosteric modulation by Na+, H+, and amiloride analogs. J Biol Chem. 1990 Oct 5;265(28):17307-17. [PubMed Link Image]
  6. Fraser CM, Arakawa S, McCombie WR, Venter JC: Cloning, sequence analysis, and permanent expression of a human alpha 2-adrenergic receptor in Chinese hamster ovary cells. Evidence for independent pathways of receptor coupling to adenylate cyclase attenuation and activation. J Biol Chem. 1989 Jul 15;264(20):11754-61. [PubMed Link Image]
  7. Kobilka BK, Matsui H, Kobilka TS, Yang-Feng TL, Francke U, Caron MG, Lefkowitz RJ, Regan JW: Cloning, sequencing, and expression of the gene coding for the human platelet alpha 2-adrenergic receptor. Science. 1987 Oct 30;238(4827):650-6. [PubMed Link Image]
Target 1 Drug References
  1. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed Link Image]
  2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed Link Image]

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.