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Identification
NameL-DOPA
Accession NumberDB01235  (APRD00309, EXPT01107)
Typesmall molecule
Groupsapproved
Description

The naturally occurring form of dihydroxyphenylalanine and the immediate precursor of dopamine. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to dopamine. It is used for the treatment of parkinsonian disorders and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
(−)-3-(3,4-dihydroxyphenyl)-L-alanineNot AvailableNot Available
(−)-dopaNot AvailableNot Available
3-Hydroxy-L-tyrosineNot AvailableNot Available
Dihydroxy-L-phenylalanineNot AvailableNot Available
L-3,4-dihydroxyphenylalanineNot AvailableNot Available
L-beta-(3,4-Dihydroxyphenyl)alanineNot AvailableNot Available
L-DOPANot AvailableNot Available
β-(3,4-dihydroxyphenyl)alanineNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
DoparNot Available
Brand mixtures
Brand NameIngredients
Atametcarbidopa + levodopa
Prolopabenserazide + levodopa
Sinemetcarbidopa + levodopa
Stalevocarbidopa + levodopa + entacapone
Categories
CAS number59-92-7
WeightAverage: 197.1879
Monoisotopic: 197.068807845
Chemical FormulaC9H11NO4
InChI KeyInChIKey=WTDRDQBEARUVNC-LURJTMIESA-N
InChI
InChI=1S/C9H11NO4/c10-6(9(13)14)3-5-1-2-7(11)8(12)4-5/h1-2,4,6,11-12H,3,10H2,(H,13,14)/t6-/m0/s1
IUPAC Name
(2S)-2-amino-3-(3,4-dihydroxyphenyl)propanoic acid
SMILES
N[C@@H](CC1=CC(O)=C(O)C=C1)C(O)=O
Mass Specshow(7.19 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassPhenols and Derivatives
Direct parentCatecholamines and Derivatives
Alternative parentsPhenylpropanoic Acids; Alpha Amino Acids and Derivatives; Amphetamines and Derivatives; Amino Fatty Acids; Polyols; Enolates; Carboxylic Acids; Polyamines; Enols; Monoalkylamines
Substituentspolyol; carboxylic acid; enolate; enol; polyamine; carboxylic acid derivative; amine; primary amine; primary aliphatic amine; organonitrogen compound
Classification descriptionThis compound belongs to the catecholamines and derivatives. These are compounds containing 4-(2-Aminoethyl)pyrocatechol [4-(2-aminoethyl)benzene-1,2-diol] or a derivative thereof formed by substitution.
Pharmacology
IndicationFor the treatment of idiopathic Parkinson's disease (Paralysis Agitans), postencephalitic parkinsonism, symptomatic parkinsonism which may follow injury to the nervous system by carbon monoxide intoxication, and manganese intoxication.
PharmacodynamicsLevodopa (L-dopa) is used to replace dopamine lost in Parkinson's disease because dopamine itself cannot cross the blood-brain barrier where its precursor can. However, L-DOPA is converted to dopamine in the periphery as well as in the CNS, so it is administered with a peripheral DDC (dopamine decarboxylase) inhibitor such as carbidopa, without which 90% is metabolised in the gut wall, and with a COMT inhibitor if possible; this prevents about a 5% loss. The form given therapeutically is therefore a prodrug which avoids decarboxylation in the stomach and periphery, can cross the blood-brain barrier, and once in the brain is converted to the neurotransmitter dopamine by the enzyme aromatic-L-amino-acid decarboxylase.
Mechanism of actionStriatal dopamine levels in symptomatic Parkinson's disease are decreased by 60 to 80%, striatal dopaminergic neurotransmission may be enhanced by exogenous supplementation of dopamine through administration of dopamine's precursor, levodopa. A small percentage of each levodopa dose crosses the blood-brain barrier and is decarboxylated to dopamine. This newly formed dopamine then is available to stimulate dopaminergic receptors, thus compensating for the depleted supply of endogenous dopamine.
AbsorptionLevodopa is rapidly absorbed from the proximal small intestine by the large neutral amino acid (LNAA) transport carrier system.
Volume of distributionNot Available
Protein bindingHigh
Metabolism

95% of an administered oral dose of levodopa is pre-systemically decarboxylated to dopamine by the L-aromatic amino acid decarboxylase (AAAD) enzyme in the stomach, lumen of the intestine, kidney, and liver. Levodopa also may be methoxylated by the hepatic catechol-O-methyltransferase (COMT) enzyme system to 3-O-methyldopa (3-OMD), which cannot be converted to central dopamine.

SubstrateEnzymesProduct
L-DOPA
    DOPA sulfateDetails
    Route of eliminationNot Available
    Half life50 to 90 minutes
    ClearanceNot Available
    ToxicityOral, mouse: LD50 = 2363 mg/kg; Oral, rabbit: LD50 = 609 mg/kg; Oral, rat: LD50 = 1780 mg/kg.
    Affected organisms
    • Humans and other mammals
    Pathways
    PathwayCategorySMPDB ID
    Disulfiram Action PathwayDrug actionSMP00429
    AlkaptonuriaDiseaseSMP00169
    Aromatic L-Aminoacid Decarboxylase DeficiencyDiseaseSMP00170
    Dopamine beta-hydroxylase deficiencyDiseaseSMP00498
    Catecholamine BiosynthesisMetabolicSMP00012
    Monoamine oxidase-a deficiency (MAO-A)DiseaseSMP00533
    Tyrosine hydroxylase deficiencyDiseaseSMP00497
    HawkinsinuriaDiseaseSMP00190
    Tyrosinemia Type IDiseaseSMP00218
    Tyrosine MetabolismMetabolicSMP00006
    Tyrosinemia, transient, of the newbornDiseaseSMP00494
    SNP Mediated EffectsNot Available
    SNP Mediated Adverse Drug ReactionsNot Available
    ADMET
    Predicted ADMET features
    Property Value Probability
    Human Intestinal Absorption + 0.8715
    Blood Brain Barrier - 0.9264
    Caco-2 permeable - 0.8957
    P-glycoprotein substrate Non-substrate 0.5734
    P-glycoprotein inhibitor I Non-inhibitor 0.989
    P-glycoprotein inhibitor II Non-inhibitor 0.988
    Renal organic cation transporter Non-inhibitor 0.9211
    CYP450 2C9 substrate Non-substrate 0.8236
    CYP450 2D6 substrate Non-substrate 0.8514
    CYP450 3A4 substrate Non-substrate 0.7117
    CYP450 1A2 substrate Non-inhibitor 0.9467
    CYP450 2C9 substrate Non-inhibitor 0.9765
    CYP450 2D6 substrate Non-inhibitor 0.9576
    CYP450 2C19 substrate Non-inhibitor 0.9504
    CYP450 3A4 substrate Non-inhibitor 0.914
    CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9713
    Ames test AMES toxic 0.9106
    Carcinogenicity Non-carcinogens 0.941
    Biodegradation Ready biodegradable 0.7332
    Rat acute toxicity 2.0131 LD50, mol/kg Not applicable
    hERG inhibition (predictor I) Weak inhibitor 0.9872
    hERG inhibition (predictor II) Non-inhibitor 0.9524
    Pharmacoeconomics
    Manufacturers
    • Valeant pharmaceuticals international
    • Shire development inc
    • Hoffmann la roche inc
    Packagers
    Dosage forms
    FormRouteStrength
    TabletOral
    Prices
    Unit descriptionCostUnit
    L-dopa powder15.19USDg
    Levodopa powder7.31USDg
    DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
    PatentsNot Available
    Properties
    Statesolid
    Experimental Properties
    PropertyValueSource
    melting point285 dec °CPhysProp
    water solubility5000 mg/L (at 20 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
    logP-2.39SANGSTER (1993)
    logS-1.6ADME Research, USCD
    pKa2.32 (at 25 °C)KORTUM,G ET AL (1961)
    Predicted Properties
    PropertyValueSource
    water solubility3.30e+00 g/lALOGPS
    logP-2.3ALOGPS
    logP-1.8ChemAxon
    logS-1.8ALOGPS
    pKa (strongest acidic)1.65ChemAxon
    pKa (strongest basic)9.06ChemAxon
    physiological charge0ChemAxon
    hydrogen acceptor count5ChemAxon
    hydrogen donor count4ChemAxon
    polar surface area103.78ChemAxon
    rotatable bond count3ChemAxon
    refractivity49.08ChemAxon
    polarizability18.91ChemAxon
    number of rings1ChemAxon
    bioavailability1ChemAxon
    rule of fiveYesChemAxon
    Ghose filterNoChemAxon
    Veber's ruleNoChemAxon
    MDDR-like ruleNoChemAxon
    Spectra
    Spectra
    References
    Synthesis Reference

    Vincenzo Cannata, Giancarlo Tamerlani, Mauro Morotti, “Process for the synthesis of the levodopa.” U.S. Patent US4962223, issued December, 1986.

    US4962223
    General Reference
    1. Pinho MJ, Serrao MP, Gomes P, Hopfer U, Jose PA, Soares-da-Silva P: Over-expression of renal LAT1 and LAT2 and enhanced L-DOPA uptake in SHR immortalized renal proximal tubular cells. Kidney Int. 2004 Jul;66(1):216-26. Pubmed
    2. Kageyama T, Nakamura M, Matsuo A, Yamasaki Y, Takakura Y, Hashida M, Kanai Y, Naito M, Tsuruo T, Minato N, Shimohama S: The 4F2hc/LAT1 complex transports L-DOPA across the blood-brain barrier. Brain Res. 2000 Oct 6;879(1-2):115-21. Pubmed
    External Links
    ResourceLink
    KEGG DrugD00059
    KEGG CompoundC00355
    PubChem Compound6047
    PubChem Substance46508120
    ChemSpider5824
    ChEBI15765
    ChEMBLCHEMBL1009
    Therapeutic Targets DatabaseDAP000209
    PharmGKBPA450213
    IUPHAR3639
    Guide to Pharmacology3639
    HETDAH
    RxListhttp://www.rxlist.com/cgi/generic3/stalevo.htm
    Drugs.comhttp://www.drugs.com/mtm/levodopa.html
    WikipediaLevodopa
    ATC CodesN04BA01N04BA04
    AHFS CodesNot Available
    PDB Entries
    FDA labelNot Available
    MSDSshow(37.5 KB)
    Interactions
    Drug Interactions
    Drug
    FosphenytoinThe hydantoin decreases the effect of levodopa
    Iron DextranIron decreases the absorption of dopa derivatives
    IsocarboxazidPossible hypertensive crisis
    MethyldopaMethyldopa increases the effect and toxicity of levodopa
    MetoclopramideLevodopa decreases the effect of metoclopramide
    PaliperidoneThe atypical antipsychotic agent, paliperidone, may decrease the therapeutic effect of the anti-Parkinson's agent, levodopa. This interaction may be due to the dopamine antagonist properties of paliperidone. Consider an alternate antipsychotic in those with Parkinson's disease or consider using clozapine or quetiapine if an atypical antipsychotic is necessary.
    PhenelzinePossible hypertensive crisis
    PhenytoinThe hydantoin decreases the effect of levodopa
    TetrabenazineTetrabenazine may cause Parkinsonian symptoms and neutralize the effect of Levodopa.
    ThiothixeneThiothixene may antaonize the effects of the anti-Parkinsonian agent, Levodopa. Consider alternate therapy or monitor for decreased effects of both agents.
    TranylcypromineLevodopa may increase the adverse effects of Tranylcypromine. Risk of severe hypertension. Concomitant therapy should be avoided or monitored closely for adverse effects of Tranylcypromine.
    ZiprasidoneThe atypical antipsychotic, ziprasidone, may antagonize the effect of the dopamine agonist, levodopa. Consider alternate therapy or monitor for worsening of movement disorder.
    ZuclopenthixolAntagonism may occur between zuclopenthixol, a dopamine D2 receptor antagonist, and levodopa, a dopamine agonist. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of both agents if concurrent therapy is initiated, discontinued or dose(s) changed.
    Zuclopenthixol acetateAntagonism may occur between zuclopenthixol, a dopamine D2 receptor antagonist, and levodopa, a dopamine agonist. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of both agents if concurrent therapy is initiated, discontinued or dose(s) changed.
    Zuclopenthixol decanoateAntagonism may occur between zuclopenthixol, a dopamine D2 receptor antagonist, and levodopa, a dopamine agonist. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of both agents if concurrent therapy is initiated, discontinued or dose(s) changed.
    Food InteractionsNot Available

    1. D(1A) dopamine receptor

    Kind: protein

    Organism: Human

    Pharmacological action: yes

    Actions: agonist

    Components

    Name UniProt ID Details
    D(1A) dopamine receptor P21728 Details

    References:

    1. Onofrj M, Bonanni L, Thomas A: An expert opinion on safinamide in Parkinson’s disease. Expert Opin Investig Drugs. 2008 Jul;17(7):1115-25. Pubmed
    2. Deleu D, Northway MG, Hanssens Y: Clinical pharmacokinetic and pharmacodynamic properties of drugs used in the treatment of Parkinson’s disease. Clin Pharmacokinet. 2002;41(4):261-309. Pubmed
    3. Koller WC, Rueda MG: Mechanism of action of dopaminergic agents in Parkinson’s disease. Neurology. 1998 Jun;50(6 Suppl 6):S11-4; discussion S44-8. Pubmed

    2. D(1B) dopamine receptor

    Kind: protein

    Organism: Human

    Pharmacological action: yes

    Actions: agonist

    Components

    Name UniProt ID Details
    D(1B) dopamine receptor P21918 Details

    References:

    1. Onofrj M, Bonanni L, Thomas A: An expert opinion on safinamide in Parkinson’s disease. Expert Opin Investig Drugs. 2008 Jul;17(7):1115-25. Pubmed
    2. Deleu D, Northway MG, Hanssens Y: Clinical pharmacokinetic and pharmacodynamic properties of drugs used in the treatment of Parkinson’s disease. Clin Pharmacokinet. 2002;41(4):261-309. Pubmed
    3. Koller WC, Rueda MG: Mechanism of action of dopaminergic agents in Parkinson’s disease. Neurology. 1998 Jun;50(6 Suppl 6):S11-4; discussion S44-8. Pubmed

    3. D(2) dopamine receptor

    Kind: protein

    Organism: Human

    Pharmacological action: yes

    Actions: agonist

    Components

    Name UniProt ID Details
    D(2) dopamine receptor P14416 Details

    References:

    1. Dupre KB, Eskow KL, Negron G, Bishop C: The differential effects of 5-HT receptor stimulation on dopamine receptor-mediated abnormal involuntary movements and rotations in the primed hemiparkinsonian rat. Brain Res. 2007 Jul 16;1158:135-43. Epub 2007 May 8. Pubmed
    2. Mori A, Ohashi S, Nakai M, Moriizumi T, Mitsumoto Y: Neural mechanisms underlying motor dysfunction as detected by the tail suspension test in MPTP-treated C57BL/6 mice. Neurosci Res. 2005 Mar;51(3):265-74. Epub 2005 Jan 8. Pubmed
    3. Zappia M, Annesi G, Nicoletti G, Arabia G, Annesi F, Messina D, Pugliese P, Spadafora P, Tarantino P, Carrideo S, Civitelli D, De Marco EV, Ciro-Candiano IC, Gambardella A, Quattrone A: Sex differences in clinical and genetic determinants of levodopa peak-dose dyskinesias in Parkinson disease: an exploratory study. Arch Neurol. 2005 Apr;62(4):601-5. Pubmed
    4. Kovoor A, Seyffarth P, Ebert J, Barghshoon S, Chen CK, Schwarz S, Axelrod JD, Cheyette BN, Simon MI, Lester HA, Schwarz J: D2 dopamine receptors colocalize regulator of G-protein signaling 9-2 (RGS9-2) via the RGS9 DEP domain, and RGS9 knock-out mice develop dyskinesias associated with dopamine pathways. J Neurosci. 2005 Feb 23;25(8):2157-65. Pubmed
    5. Onofrj M, Bonanni L, Thomas A: An expert opinion on safinamide in Parkinson’s disease. Expert Opin Investig Drugs. 2008 Jul;17(7):1115-25. Pubmed
    6. Deleu D, Northway MG, Hanssens Y: Clinical pharmacokinetic and pharmacodynamic properties of drugs used in the treatment of Parkinson’s disease. Clin Pharmacokinet. 2002;41(4):261-309. Pubmed
    7. Koller WC, Rueda MG: Mechanism of action of dopaminergic agents in Parkinson’s disease. Neurology. 1998 Jun;50(6 Suppl 6):S11-4; discussion S44-8. Pubmed

    4. D(3) dopamine receptor

    Kind: protein

    Organism: Human

    Pharmacological action: yes

    Actions: agonist

    Components

    Name UniProt ID Details
    D(3) dopamine receptor P35462 Details

    References:

    1. Onofrj M, Bonanni L, Thomas A: An expert opinion on safinamide in Parkinson’s disease. Expert Opin Investig Drugs. 2008 Jul;17(7):1115-25. Pubmed
    2. Deleu D, Northway MG, Hanssens Y: Clinical pharmacokinetic and pharmacodynamic properties of drugs used in the treatment of Parkinson’s disease. Clin Pharmacokinet. 2002;41(4):261-309. Pubmed
    3. Koller WC, Rueda MG: Mechanism of action of dopaminergic agents in Parkinson’s disease. Neurology. 1998 Jun;50(6 Suppl 6):S11-4; discussion S44-8. Pubmed

    5. D(4) dopamine receptor

    Kind: protein

    Organism: Human

    Pharmacological action: yes

    Actions: agonist

    Components

    Name UniProt ID Details
    D(4) dopamine receptor P21917 Details

    References:

    1. Onofrj M, Bonanni L, Thomas A: An expert opinion on safinamide in Parkinson’s disease. Expert Opin Investig Drugs. 2008 Jul;17(7):1115-25. Pubmed
    2. Deleu D, Northway MG, Hanssens Y: Clinical pharmacokinetic and pharmacodynamic properties of drugs used in the treatment of Parkinson’s disease. Clin Pharmacokinet. 2002;41(4):261-309. Pubmed
    3. Koller WC, Rueda MG: Mechanism of action of dopaminergic agents in Parkinson’s disease. Neurology. 1998 Jun;50(6 Suppl 6):S11-4; discussion S44-8. Pubmed

    1. Aromatic-L-amino-acid decarboxylase

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Components

    Name UniProt ID Details
    Aromatic-L-amino-acid decarboxylase P20711 Details

    References:

    1. BIRKMAYER W, HORNYKIEWICZ O: [The L-3,4-dioxyphenylalanine (DOPA)-effect in Parkinson-akinesia]. Wien Klin Wochenschr. 1961 Nov 10;73:787-8. Pubmed

    2. Cytochrome P450 2D6

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: substrate

    Components

    Name UniProt ID Details
    Cytochrome P450 2D6 P10635 Details

    References:

    1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

    1. Solute carrier family 15 member 1

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: inhibitor

    Components

    Name UniProt ID Details
    Solute carrier family 15 member 1 P46059 Details

    References:

    1. Han HK, Rhie JK, Oh DM, Saito G, Hsu CP, Stewart BH, Amidon GL: CHO/hPEPT1 cells overexpressing the human peptide transporter (hPEPT1) as an alternative in vitro model for peptidomimetic drugs. J Pharm Sci. 1999 Mar;88(3):347-50. Pubmed
    2. Tamai I, Nakanishi T, Nakahara H, Sai Y, Ganapathy V, Leibach FH, Tsuji A: Improvement of L-dopa absorption by dipeptidyl derivation, utilizing peptide transporter PepT1. J Pharm Sci. 1998 Dec;87(12):1542-6. Pubmed

    2. Monocarboxylate transporter 10

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: inhibitor

    Components

    Name UniProt ID Details
    Monocarboxylate transporter 10 Q8TF71 Details

    References:

    1. Kim DK, Kanai Y, Chairoungdua A, Matsuo H, Cha SH, Endou H: Expression cloning of a Na+-independent aromatic amino acid transporter with structural similarity to H+/monocarboxylate transporters. J Biol Chem. 2001 May 18;276(20):17221-8. Epub 2001 Feb 20. Pubmed

    3. Large neutral amino acids transporter small subunit 1

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Components

    Name UniProt ID Details
    Large neutral amino acids transporter small subunit 1 Q01650 Details

    References:

    1. Pinho MJ, Serrao MP, Gomes P, Hopfer U, Jose PA, Soares-da-Silva P: Over-expression of renal LAT1 and LAT2 and enhanced L-DOPA uptake in SHR immortalized renal proximal tubular cells. Kidney Int. 2004 Jul;66(1):216-26. Pubmed
    2. Kageyama T, Nakamura M, Matsuo A, Yamasaki Y, Takakura Y, Hashida M, Kanai Y, Naito M, Tsuruo T, Minato N, Shimohama S: The 4F2hc/LAT1 complex transports L-DOPA across the blood-brain barrier. Brain Res. 2000 Oct 6;879(1-2):115-21. Pubmed

    4. Large neutral amino acids transporter small subunit 2

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Components

    Name UniProt ID Details
    Large neutral amino acids transporter small subunit 2 Q9UHI5 Details

    References:

    1. Pinho MJ, Serrao MP, Gomes P, Hopfer U, Jose PA, Soares-da-Silva P: Over-expression of renal LAT1 and LAT2 and enhanced L-DOPA uptake in SHR immortalized renal proximal tubular cells. Kidney Int. 2004 Jul;66(1):216-26. Pubmed

    Comments
    Drug created on June 13, 2005 07:24 / Updated on January 10, 2014 11:59