General
Preferred name
LEVODOPA
Synonyms
L-3,4-Dihydroxyphenylalanine ()
L-DOPA ()
L-3,4-DIHYDROXYPHENYL-ALANINE ()
3,4-Dihydroxyphenylalanine ()
L-DOPA-d3 ()
Levodopa component of rytary ()
Cvt-301 ()
Levodopa component of corbilta ()
Levodopa component of crexont ()
Brocadopa ()
Larodopa ()
Levodopum ()
Levodopa component of duopa ()
Levodopa component of ipx203 ()
Levodopa component of stalevo ()
Levodopa component of parcopa ()
Levodopa component of sinemet ()
Levodopa component of dopasnap ()
V-1512 ()
Bendopa ()
Levodopa component of ipx-203 ()
Levodopa component of dhivy ()
Levodopa component of carbilev ()
Dopar ()
Levodopa component of /carbidopa/entacapone orion ()
Inbrija ()
NSC-118381 ()
Deuterium-substituted L-DOPA ()
P&D ID
PD000068
CAS
587-45-1
23734-74-9
122769-74-8
59-92-7
53587-29-4
Tags
available
prodrug
drug
Approved by
FDA
EMA
First approval
1970
Drug indication
cocaine dependence
Parkinson disease
Drug Status
approved
Max Phase
4.0
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness 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 of the catecholamine dopamine neurotransmitters. It has been isolated as a naturally ocurring metabolite from Vicia faba (broad bean or fava) beans . Note a deuterated derivative D3 L-DOPA with enhanced properties is under development.
(GtoPdb)
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].
PRICE
29
DESCRIPTION
L-DOPA (Levodopa) is an amino acid precursor of dopamine with antiparkinsonian properties. It is a prodrug converted to dopamine by DOPA decarboxylase and can cross the blood-brain barrier. In the brain, levodopa is decarboxylated to dopamine, stimulating dopaminergic receptors and compensating for depleted endogenous dopamine in Parkinson's disease. To ensure adequate concentrations reach the central nervous system, levodopa is administered with carbidopa, a decarboxylase inhibitor that does not cross the blood-brain barrier, reducing peripheral decarboxylation and increasing CNS dopamine delivery.
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
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.
DESCRIPTION
Selective, non-peptide AT1 antagonist
(Tocris Bioactive Compound Library)
DESCRIPTION
Precursor to dopamine; antiparkinsonian agent
(LOPAC library)
DESCRIPTION
Levodopa is a prodrug of dopamine that is administered to patients with Parkinson's due to its ability to cross the blood-brain barrier. Levodopa can be metabolised to dopamine on either side of the blood-brain barrier and so it is generally administered with a dopa decarboxylase inhibitor like carbidopa to prevent metabolism until after it has crossed the blood-brain barrier.
(Enamine Bioactive Compounds)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Compound Sets
29
ChEMBL Approved Drugs
ChEMBL Drugs
Concise Guide to Pharmacology 2017/18
Concise Guide to Pharmacology 2019/20
Concise Guide to Pharmacology 2021/22
Concise Guide to Pharmacology 2023/24
Drug Repurposing Hub
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP
DrugMAP Approved Drugs
Enamine Bioactive Compounds
Enamine BioReference Compounds
LOPAC library
LSP-MoA library (Laboratory of Systems Pharmacology)
Mcule NIBR MoA Box Subset
MedChem Express Bioactive Compound Library
NCATS Inxight Approved Drugs
Novartis Chemogenetic Library (NIBR MoA Box)
NPC Screening Collection
Prestwick Chemical Library
ReFrame library
The Spectrum Collection
Tocris Bioactive Compound Library
ZINC Tool Compounds
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
92
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)
Primary Target
Non-selective Dopamine
MOA
Dopamine Receptor agonist
Dopamine Precursors
dopamine precursor
Member status
member
Target
DRD1, DRD2, DRD3, DRD4, DRD5, GPR143
Dopamine Receptor
Endogenous Metabolite
Indication
Parkinson's Disease
Pathway
GPCR/G protein
Metabolic Enzyme/Protease
Neuronal Signaling
Source data
