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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
Brand names
  • 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
Brand name mixtures
  • 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 (7.2 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.
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
Patents Not Available
Properties
State solid
Melting point 276-278 oC
Experimental Properties
Property Value Source
water solubility 5000 mg/L PhysProp
logP -1.8 PhysProp
logS -1.6 [ADME Research, USCD] PhysProp
pKa 2.32 Various sources
Predicted Properties
Property Value Source
water solubility 3.30e+00 g/l ALOGPS
logP -2.32 ALOGPS
logP -1.93 ChemAxon Molconvert
logS -1.78 ALOGPS
pKa 9.69 ChemAxon Molconvert
hydrogen acceptor count 5 ChemAxon Molconvert
hydrogen donor count 4 ChemAxon Molconvert
polar surface area 103.78 ChemAxon Molconvert
rotatable bond count 3 ChemAxon Molconvert
refractivity 49.08 ChemAxon Molconvert
polarizability 18.91 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
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
HET DAH Link_out
Drug Product Database 0 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 Not Available
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. 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
Comments
Drug created on June 13, 2005 07:24 / Updated on October 05, 2011 15:51

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.