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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-(3,4-dihydroxyphenyl)-L-alanineNot AvailableNot Available
(−)-dopaNot AvailableNot Available
3-Hydroxy-L-tyrosineNot AvailableNot Available
3,4-Dihydroxy-L-phenylalanineNot AvailableNot Available
3,4-DIHYDROXYPHENYLALANINENot AvailableNot Available
beta-(3,4-Dihydroxyphenyl)-L-alanineNot AvailableNot Available
beta-(3,4-Dihydroxyphenyl)alanineNot AvailableNot Available
Dihydroxy-L-phenylalanineNot AvailableNot Available
DoparNot AvailableNot Available
L-3,4-dihydroxyphenylalanineNot AvailableNot Available
L-beta-(3,4-Dihydroxyphenyl)alanineNot AvailableNot Available
L-DOPANot AvailableNot Available
LevodopaNot AvailableNot Available
LevodopumNot AvailableNot Available
β-(3,4-dihydroxyphenyl)alanineNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
BidopalGlaxoSmithKline
DoparNot Available
DoparlKyowa Hakko Kirin
DopasolDaiichi Sankyo
DopastonOhara Yakuhin
Brand mixtures
Brand NameIngredients
Atametcarbidopa + levodopa
DuodopaLevodopa and Carbidopa
MadoparLevodopa and Benserazide
MenkartLevodopa and Benserazide
ParcopaCarbidopa + L-DOPA
Prolopabenserazide + levodopa
Sinemetcarbidopa + levodopa
Sinemet CRLevodopa and Carbidopa
Stalevocarbidopa + levodopa + entacapone
Categories
CAS number59-92-7
WeightAverage: 197.1879
Monoisotopic: 197.068807845
Chemical FormulaC9H11NO4
InChI KeyWTDRDQBEARUVNC-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
Not Available
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
Monoamine oxidase-a deficiency (MAO-A)DiseaseSMP00533
Disulfiram Action PathwayDrug actionSMP00429
AlkaptonuriaDiseaseSMP00169
Aromatic L-Aminoacid Decarboxylase DeficiencyDiseaseSMP00170
Dopamine beta-hydroxylase deficiencyDiseaseSMP00498
Catecholamine BiosynthesisMetabolicSMP00012
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 point284-285U.S. Patent 3,253,023.
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
SpectraGC-MSMS/MSLC-MS1D NMR2D NMR
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

Targets

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

Enzymes

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

Transporters

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

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