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Identification
Name Levodopa
Accession Number DB01235 (APRD00309, EXPT01107)
Type small molecule
Groups approved
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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
3,4-dihydroxyphenylalanine
DOPA
L-Dihydroxyphenylalanine
L-DOPA
Salts Not Available
Brand names
Name Company
Bendopa
Brocadopa
Cidandopa
Deadopa
Dopaflex
Dopaidan
Dopal
Dopal-Fher
Dopalina
Dopar
Doparkine
Doparl
Dopasol
Dopaston
Dopastral
Doprin
Eldopal
Eldopar
Eldopatec
Eurodopa
Helfo-Dopa
Insulamina
Laradopa
Larodopa
Ledopa
Levedopa
Levopa
Maipedopa
Parda
Pardopa
Prodopa
Syndopa
Veldopa
Weldopa
First Prev Next Last
Brand mixtures
Brand Name Ingredients
Apo-Levocarb CR Controlled-Release Tablets carbidopa + levodopa
Dom-Levo-Carbidopa carbidopa + levodopa
Novo-Levocarbidopa carbidopa + levodopa
Pro-Lecarb-100/10 - Tab carbidopa + levodopa
Pro-Lecarb-100/25 - Tab carbidopa + levodopa
Prolopa Cap 50-12.5 Benserazide + Levodopa
Ratio-Levodopa/Carbidopa carbidopa + levodopa
Sinemet carbidopa + levodopa
Sinemet CR carbidopa + levodopa
Categories
  • Dopamine Agents
  • Antiparkinson Agents
  • Antidyskinetics
CAS number 59-92-7
Weight Average: 197.1879
Monoisotopic: 197.068807845
Chemical Formula C9H11NO4
InChI Key InChIKey=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
Plain Text
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
Plain Text
Mass Spec show (7.19 KB)
Taxonomy
Kingdom Not Available
Classes
  • Phenols and Derivatives
  • Amino Acids
  • Amphetamines
  • Catecholamines and Derivatives
Substructures
  • Hydroxy Compounds
  • Phenols and Derivatives
  • Acetates
  • Aliphatic and Aryl Amines
  • Benzene and Derivatives
  • Carboxylic Acids and Derivatives
  • Catechols
  • Phenethylamines
  • Aromatic compounds
  • Amino Acids
  • Phenyl Esters
  • Amphetamines
  • Catecholamines and Derivatives
Pharmacology
Indication For 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.
Pharmacodynamics Levodopa (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 action Striatal 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.
Absorption Levodopa is rapidly absorbed from the proximal small intestine by the large neutral amino acid (LNAA) transport carrier system.
Volume of distribution Not Available
Protein binding High
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.

Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.

Substrate Enzymes Product
Levodopa
    		DOPA sulfate Details
    Route of elimination Not Available
    Half life 50 to 90 minutes
    Clearance Not Available
    Toxicity Oral, mouse: LD50 = 2363 mg/kg; Oral, rabbit: LD50 = 609 mg/kg; Oral, rat: LD50 = 1780 mg/kg.
    Affected organisms
    • Humans and other mammals
    Pathways Not Available
    Pharmacoeconomics
    Manufacturers
    • Valeant pharmaceuticals international
    • Shire development inc
    • Hoffmann la roche inc
    Packagers
    Dosage forms
    Form Route Strength
    Tablet Oral
    Prices
    Unit description Cost Unit
    L-dopa powder 15.19 USD g
    Levodopa powder 7.31 USD g
    DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
    Patents Not Available
    Properties
    State solid
    Experimental Properties
    Property Value Source
    melting point 285 dec °C PhysProp
    water solubility 5000 mg/L (at 20 °C) YALKOWSKY,SH & DANNENFELSER,RM (1992)
    logP -2.39 SANGSTER (1993)
    logS -1.6 ADME Research, USCD
    pKa 2.32 (at 25 °C) KORTUM,G ET AL (1961)
    Predicted Properties
    Property Value Source
    water solubility 3.30e+00 g/l ALOGPS
    logP -2.3 ALOGPS
    logP -1.8 ChemAxon
    logS -1.8 ALOGPS
    pKa (strongest acidic) 1.65 ChemAxon
    pKa (strongest basic) 9.06 ChemAxon
    physiological charge 0 ChemAxon
    hydrogen acceptor count 5 ChemAxon
    hydrogen donor count 4 ChemAxon
    polar surface area 103.78 ChemAxon
    rotatable bond count 3 ChemAxon
    refractivity 49.08 ChemAxon
    polarizability 18.91 ChemAxon
    References
    Synthesis Reference Not Available
    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
    Resource Link
    KEGG Drug D00059 Link_out
    KEGG Compound C00355 Link_out
    PubChem Compound 6047 Link_out
    PubChem Substance 46508120 Link_out
    ChemSpider 5824 Link_out
    ChEBI 15765 Link_out
    ChEMBL 15765 Link_out
    Therapeutic Targets Database DAP000209 Link_out
    PharmGKB PA450213 Link_out
    IUPHAR 3639 Link_out
    Guide to Pharmacology 3639 Link_out
    HET DAH Link_out
    RxList http://www.rxlist.com/cgi/generic3/stalevo.htm Link_out
    Drugs.com http://www.drugs.com/mtm/levodopa.html Link_out
    Wikipedia http://en.wikipedia.org/wiki/Levodopa Link_out
    ATC Codes
    • N04BA01
    • N04BA04
    AHFS Codes Not Available
    PDB Entries
    FDA label Not Available
    MSDS show (37.5 KB)
    Interactions
    Drug Interactions
    Drug Interaction
    Fosphenytoin The hydantoin decreases the effect of levodopa
    Iron Dextran Iron decreases the absorption of dopa derivatives
    Isocarboxazid Possible hypertensive crisis
    Methyldopa Methyldopa increases the effect and toxicity of levodopa
    Metoclopramide Levodopa decreases the effect of metoclopramide
    Paliperidone The 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.
    Phenelzine Possible hypertensive crisis
    Phenytoin The hydantoin decreases the effect of levodopa
    Tetrabenazine Tetrabenazine may cause Parkinsonian symptoms and neutralize the effect of Levodopa.
    Thiothixene Thiothixene may antaonize the effects of the anti-Parkinsonian agent, Levodopa. Consider alternate therapy or monitor for decreased effects of both agents.
    Tranylcypromine Levodopa may increase the adverse effects of Tranylcypromine. Risk of severe hypertension. Concomitant therapy should be avoided or monitored closely for adverse effects of Tranylcypromine.
    Ziprasidone The atypical antipsychotic, ziprasidone, may antagonize the effect of the dopamine agonist, levodopa. Consider alternate therapy or monitor for worsening of movement disorder.
    Zuclopenthixol Antagonism 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 Interactions Not Available
    Targets

    1. D(1A) dopamine receptor

    Pharmacological action: yes
    Actions: agonist

    This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase

    Organism class: human
    UniProt ID: P21728 Link_out
    Gene: DRD1 Link_out
    Protein Sequence: FASTA
    Gene Sequence: FASTA
    SNPs: SNPJam Report Link_out

    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

    Pharmacological action: yes
    Actions: agonist

    This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase

    Organism class: human
    UniProt ID: P21918 Link_out
    Gene: DRD5 Link_out
    Protein Sequence: FASTA
    Gene Sequence: FASTA
    SNPs: SNPJam Report Link_out

    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

    Pharmacological action: yes
    Actions: agonist

    This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase

    Organism class: human
    UniProt ID: P14416 Link_out
    Gene: DRD2 Link_out
    Protein Sequence: FASTA
    Gene Sequence: FASTA
    SNPs: SNPJam Report Link_out

    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

    Pharmacological action: yes
    Actions: agonist

    This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase

    Organism class: human
    UniProt ID: P35462 Link_out
    Gene: DRD3 Link_out
    Protein Sequence: FASTA
    Gene Sequence: FASTA
    SNPs: SNPJam Report Link_out

    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

    Pharmacological action: yes
    Actions: agonist

    This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase

    Organism class: human
    UniProt ID: P21917 Link_out
    Gene: DRD4 Link_out
    Protein Sequence: FASTA
    Gene Sequence: FASTA
    SNPs: SNPJam Report Link_out

    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

    Catalyzes the decarboxylation of L-3,4- dihydroxyphenylalanine (DOPA) to dopamine, L-5-hydroxytryptophan to serotonin and L-tryptophan to tryptamine

    UniProt ID: P20711 Link_out
    Gene: DDC Link_out
    Protein Sequence: FASTA
    Gene Sequence: FASTA
    SNPs: SNPJam Report Link_out

    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

    Actions: substrate

    Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants

    UniProt ID: P10635 Link_out
    Gene: CYP2D6 Link_out
    Protein Sequence: FASTA
    Gene Sequence: FASTA
    SNPs: SNPJam Report Link_out

    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. Oligopeptide transporter, small intestine isoform

    Actions: inhibitor

    Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides. May constitute a major route for the absorption of protein digestion end-products

    UniProt ID: P46059 Link_out
    Gene: SLC15A1 Link_out
    Protein Sequence: FASTA
    Gene Sequence: FASTA
    SNPs: SNPJam Report Link_out

    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

    Actions: inhibitor

    Sodium-independent transporter that mediates the update of aromatic acid. Can function as a net efflux pathway for aromatic amino acids in the basosolateral epithelial cells (By similarity)

    UniProt ID: Q8TF71 Link_out
    Gene: SLC16A10 Link_out
    Protein Sequence: FASTA
    Gene Sequence: FASTA
    SNPs: SNPJam Report Link_out

    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

    Sodium-independent, high-affinity transport of large neutral amino acids. Involved in cellular amino acid uptake

    UniProt ID: Q01650 Link_out
    Gene: SLC7A5 Link_out
    Protein Sequence: FASTA
    Gene Sequence: FASTA
    SNPs: SNPJam Report Link_out

    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

    Sodium-independent, high-affinity transport of large neutral amino acids. Has higher affinity for L-phenylalanine than LAT1 but lower affinity for glutamine and serine. L-alanine is transported at physiological concentrations. Plays a role in basolateral (re)absorption of neutral amino acids

    UniProt ID: Q9UHI5 Link_out
    Gene: SLC7A8 Link_out
    Protein Sequence: FASTA
    Gene Sequence: FASTA
    SNPs: SNPJam Report Link_out

    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 February 17, 2013 16:40