General
Preferred name
LEVODOPA
Synonyms
L-3,4-Dihydroxyphenylalanine ()
3,4-Dihydroxyphenylalanine ()
L-DOPA ()
L-3,4-DIHYDROXYPHENYL-ALANINE ()
V-1512 ()
NSC-118381 ()
Levodopum ()
Cvt-301 ()
Dopar ()
Larodopa ()
Bendopa ()
Inbrija ()
Brocadopa ()
Deuterium-substituted L-DOPA ()
L-DOPA-d3 ()
P&D ID
PD000068
CAS
587-45-1
23734-74-9
122769-74-8
59-92-7
53587-29-4
Tags
prodrug
natural product
drug
available
Approved by
EMA
FDA
First approval
1970
Drug Status
approved
Drug indication
Antiparkinsonian
Parkinson disease
Max Phase
Phase 4
Structure
Probe scores
P&D probe-likeness score
[[ v.score ]]%
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
ROE After 48 hours, 0.17% of an orally administered dose is recovered in stool, 0.28% is exhaled, and 78.4% is recovered in urine[A177805]
INDICATION Levodopa on its own is formulated as an oral inhalation powder indicated for intermittent treatment of off episodes in Parkinson's patients who are already being treated with carbidopa and levodopa[FDA Label]. Levodopa is most commonly formulated as an oral tablet with a peripheral dopa decarboxylase inhibitor indicated for treatment of Parkinson's disease, post-encephalitic parkinsonism, and symptomatic parkinsonism following carbon monoxide intoxication or manganese intoxication[F4579].
MOA Levodopa by various routes crosses the blood brain barrier, is decarboxylated to form dopamine[Label,F4579]. This supplemental dopamine performs the role that endogenous dopamine cannot due to a decrease of natural concentrations and stimulates dopaminergic receptors[Label,F4579].
HALF-LIFE 2.3 hours for orally inhaled levodopa[FDA Label]. Oral levodopa has a half life of 50 minutes but when combined with a peripheral dopa decarboxylase inhibitor, the half life is increased to 1.5 hours[F4579].
TOXICITY There is no readily available data for the use of levodopa in pregnancy[Label]. Rabbits treated with levodopa and carbidopa produced smaller litters and their offspring developed visceral and skeletal deformities[Label]. Levodopa may lower prolactin and interfere with lactation but there is limited human data to demonstrate this effect[Label]. Levodopa is present in human breast milk and so the potential effects of nursing while taking levodopa should be considered before prescribing levodopa to nursing mothers[Label]. There is currently a lack of data on the safety and effectiveness of using levodopa in pediatric patients[Label]. Patients over 65 years of age are more likely to experience adverse effects associated with taking levodopa, however this generally is not sufficient to exclude this patient group from treatment[Label].
METABOLISM Levodopa is either converted to dopamine by aromatic-L-amino-acid decarboxylase or O-methylated to 3-O-methyldopa by catechol-O-methyltransferase[Label,A177745,A177733]. 3-O-methyldopa cannot be metabolized to dopamine[A177733]. Once levodopa is converted to dopamine, it is converted to sulfated or glucuronidated metabolites, epinephrine E, or homovanillic acid through various metabolic processes[A177745]. The primary metabolites are 3,4-dihydroxyphenylacetic acid (13-47%) and homovanillic acid (23-39%)[A177733,A177805].
ABSORPTION Orally inhaled levodopa reaches a peak concentration in 0.5 hours with a bioavailability than is 70% that of the immediate release levodopa tablets with a peripheral dopa decarboxylase inhibitor like carbidopa or benserazide[Label,A177781].
DESCRIPTION L-DOPA is the precursor to the neurotransmitters dopamine collectively known as catecholamines. Used in the treatment of Parkisons disease. Note a deuterated derivative D3 L-DOPA with enhanced properties is under development. (GtoPdb)
DESCRIPTION Chronic treatment with a substantially lower dose of deuterium-substituted L-DOPA (D3-L-DOPA), compared with L-DOPA, (levodopa) produced equal anti-parkinsonian effect and reduced dyskinesia in 6-OHDA-lesioned rats . This new rat study reports similar effect produced by D3-L-DOPA and selegiline plus L-DOPA, respectively, implying adjuvant MAO-B inhibitor treatment may not be necessary with D3-L-DOPA . This compound was proposed for development by the Michael J Fox foundation but there is no clinicaltrials.gov entry.
PHARMACODYNAMICS Levodopa is able to cross the blood-brain barrier while dopamine is not[FDA Label,F4579]. The addition of a peripheral dopa decarboxylase inhibitor prevents the conversion of levodopa to dopamine in the periphery so that more levodopa can reach the blood-brain barrier[Label,F4579]. Once past the blood-brain barrier, levodopa is converted to dopamine by aromatic-L-amino-acid decarboxylase[Label,F4579].
DESCRIPTION Chronic treatment with a substantially lower dose of deuterium-substituted L-DOPA (D3-L-DOPA), compared with L-DOPA () produced equal anti-parkinsonian effects and reduced dyskinesia in 6-OHDA-lesioned rats . This new rat study reports similar effect produced by D3-L-DOPA and selegiline plus L-DOPA, respectively, implying adjuvant MAO-B inhibitor treatment may not be necessary with D3-L-DOPA . This compound was proposed for development by the Michael J Fox foundation but there is no ClinicalTrials.gov entry. (GtoPdb)
DESCRIPTION Selective, non-peptide AT1 antagonist (Tocris Bioactive Compound Library)
DESCRIPTION Precursor to dopamine; antiparkinsonian agent (LOPAC library)
Compound Sets
29
Cayman Chemical Bioactives
13248
22089
ChEMBL Approved Drugs
CHEMBL1009
ChEMBL Drugs
CHEMBL1009
Concise Guide to Pharmacology 2017/18
3639
Concise Guide to Pharmacology 2019/20
3639
Concise Guide to Pharmacology 2021/22
3639
Concise Guide to Pharmacology 2023/24
3639
Drug Repurposing Hub
DrugBank
DB01235
DrugBank Approved Drugs
DB01235
DrugCentral
1567
DrugCentral Approved Drugs
1567
DrugMAP
DMN3E57
DrugMAP Approved Drugs
DMN3E57
Enamine BioReference Compounds
Guide to Pharmacology
3639
8611
LOPAC library
LSP-MoA library (Laboratory of Systems Pharmacology)
CHEMBL1009
Mcule NIBR MoA Box Subset
MCULE-8112075430
MedChem Express Bioactive Compound Library
HY-N0304
NCATS Inxight Approved Drugs
46627O600J
Novartis Chemogenetic Library (NIBR MoA Box)
NPC Screening Collection
Prestwick Chemical Library
ReFrame library
TargetMol Bioactive Compound Library
T0848
The Spectrum Collection
Tocris Bioactive Compound Library
3788
ZINC Tool Compounds
ZINC000000895199
External IDs
88
Properties
(calculated by RDKit )
Molecular Weight
197.07
Hydrogen Bond Acceptors
4
Hydrogen Bond Donors
4
Rotatable Bonds
3
Ring Count
1
Aromatic Ring Count
1
cLogP
0.05
TPSA
103.78
Fraction CSP3
0.22
Chiral centers
1.0
Largest ring
6.0
QED
0.51
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Pathway
GPCR/G protein
Neuroscience
Metabolic Enzyme/Protease
Neuronal Signaling
Target
dopamine
DRD1, DRD2, DRD3, DRD4, DRD5, GPR143
Dopamine Receptor
Endogenous Metabolite
Primary Target
Non-selective Dopamine
MOA
Dopamine Receptor agonist
Dopamine Precursors
dopamine precursor
Member status
member
Indication
Parkinson's Disease
Source data