U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C10H13NO4
Molecular Weight 211.2145
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of MELEVODOPA

SMILES

COC(=O)[C@@H](N)CC1=CC(O)=C(O)C=C1

InChI

InChIKey=XBBDACCLCFWBSI-ZETCQYMHSA-N
InChI=1S/C10H13NO4/c1-15-10(14)7(11)4-6-2-3-8(12)9(13)5-6/h2-3,5,7,12-13H,4,11H2,1H3/t7-/m0/s1

HIDE SMILES / InChI

Description
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/23948989 http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021485s20lbl.pdf

Levodopa (L-DOPA) was first isolated from seedlings of Vicia faba by Marcus Guggenheim in 1913. Levodopa, a dopamine precursor, is an effective and well-tolerated dopamine replacement agent used to treat Parkinson's disease. Oral levodopa has been widely used for over 40 years, often in combination with a dopa-decarboxylase inhibitor carbidopa, which reduces many treatment complications, extending its half-life and increasing levodopa availability to the brain. Entacapone, a catechol-O-methyltransferase inhibitor, can also be used to improve the bioavailability of levodopa, especially when used in conjunction with a carbidopa.

Originator

Curator's Comment: # Hoffmann-La Roche

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Stalevo

Approved Use

Stalevo® (carbidopa, levodopa and entacapone) is indicated to treat patients with idiopathic Parkinson’s disease.

Launch Date

2003
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
0.946 μg/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered: CARBIDOPA, DL-
LEVODOPA plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
84.8 μg × min/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered: CARBIDOPA, DL-
LEVODOPA plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
78.7 min
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered: CARBIDOPA, DL-
LEVODOPA plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
80%
LEVODOPA plasma
Homo sapiens
Doses

Doses

DosePopulationAdverse events​
3 g 1 times / day multiple, oral
Dose: 3 g, 1 times / day
Route: oral
Route: multiple
Dose: 3 g, 1 times / day
Sources:
unhealthy, 54 years
n = 1
Health Status: unhealthy
Condition: idiopathic Parkinson's disease
Age Group: 54 years
Sex: F
Population Size: 1
Sources:
Disc. AE: Alopecia...
AEs leading to
discontinuation/dose reduction:
Alopecia (1 patient)
Sources:
420 mg 1 times / day multiple, respiratory
Recommended
Dose: 420 mg, 1 times / day
Route: respiratory
Route: multiple
Dose: 420 mg, 1 times / day
Sources:
unhealthy, adult
84 mg 2 times / day multiple, respiratory
Recommended
Dose: 84 mg, 2 times / day
Route: respiratory
Route: multiple
Dose: 84 mg, 2 times / day
Sources:
unhealthy, adult
n = 114
Health Status: unhealthy
Condition: Parkinson’s disease
Age Group: adult
Population Size: 114
Sources:
Disc. AE: Cough...
AEs leading to
discontinuation/dose reduction:
Cough (2%)
Sources:
0.51 mg/kg 3 times / day steady, oral
Dose: 0.51 mg/kg, 3 times / day
Route: oral
Route: steady
Dose: 0.51 mg/kg, 3 times / day
Sources:
unhealthy, child|adult
n = 15
Health Status: unhealthy
Condition: Vision Impairment
Age Group: child|adult
Population Size: 15
Sources:
Other AEs: Headache, Nausea...
Other AEs:
Headache (below serious, 2 patients)
Nausea (below serious, 2 patients)
Sources:
0.76 mg/kg 3 times / day steady, oral
Dose: 0.76 mg/kg, 3 times / day
Route: oral
Route: steady
Dose: 0.76 mg/kg, 3 times / day
Sources:
unhealthy, child|adult
n = 15
Health Status: unhealthy
Condition: Vision Impairment
Age Group: child|adult
Population Size: 15
Sources:
Other AEs: Headache, Dry mouth...
Other AEs:
Headache (below serious, 1 patient)
Dry mouth (below serious, 2 patients)
Nausea (below serious, 1 patient)
Fatigue (below serious, 2 patients)
Sources:
AEs

AEs

AESignificanceDosePopulation
Alopecia 1 patient
Disc. AE
3 g 1 times / day multiple, oral
Dose: 3 g, 1 times / day
Route: oral
Route: multiple
Dose: 3 g, 1 times / day
Sources:
unhealthy, 54 years
n = 1
Health Status: unhealthy
Condition: idiopathic Parkinson's disease
Age Group: 54 years
Sex: F
Population Size: 1
Sources:
Cough 2%
Disc. AE
84 mg 2 times / day multiple, respiratory
Recommended
Dose: 84 mg, 2 times / day
Route: respiratory
Route: multiple
Dose: 84 mg, 2 times / day
Sources:
unhealthy, adult
n = 114
Health Status: unhealthy
Condition: Parkinson’s disease
Age Group: adult
Population Size: 114
Sources:
Headache below serious, 2 patients
0.51 mg/kg 3 times / day steady, oral
Dose: 0.51 mg/kg, 3 times / day
Route: oral
Route: steady
Dose: 0.51 mg/kg, 3 times / day
Sources:
unhealthy, child|adult
n = 15
Health Status: unhealthy
Condition: Vision Impairment
Age Group: child|adult
Population Size: 15
Sources:
Nausea below serious, 2 patients
0.51 mg/kg 3 times / day steady, oral
Dose: 0.51 mg/kg, 3 times / day
Route: oral
Route: steady
Dose: 0.51 mg/kg, 3 times / day
Sources:
unhealthy, child|adult
n = 15
Health Status: unhealthy
Condition: Vision Impairment
Age Group: child|adult
Population Size: 15
Sources:
Headache below serious, 1 patient
0.76 mg/kg 3 times / day steady, oral
Dose: 0.76 mg/kg, 3 times / day
Route: oral
Route: steady
Dose: 0.76 mg/kg, 3 times / day
Sources:
unhealthy, child|adult
n = 15
Health Status: unhealthy
Condition: Vision Impairment
Age Group: child|adult
Population Size: 15
Sources:
Nausea below serious, 1 patient
0.76 mg/kg 3 times / day steady, oral
Dose: 0.76 mg/kg, 3 times / day
Route: oral
Route: steady
Dose: 0.76 mg/kg, 3 times / day
Sources:
unhealthy, child|adult
n = 15
Health Status: unhealthy
Condition: Vision Impairment
Age Group: child|adult
Population Size: 15
Sources:
Dry mouth below serious, 2 patients
0.76 mg/kg 3 times / day steady, oral
Dose: 0.76 mg/kg, 3 times / day
Route: oral
Route: steady
Dose: 0.76 mg/kg, 3 times / day
Sources:
unhealthy, child|adult
n = 15
Health Status: unhealthy
Condition: Vision Impairment
Age Group: child|adult
Population Size: 15
Sources:
Fatigue below serious, 2 patients
0.76 mg/kg 3 times / day steady, oral
Dose: 0.76 mg/kg, 3 times / day
Route: oral
Route: steady
Dose: 0.76 mg/kg, 3 times / day
Sources:
unhealthy, child|adult
n = 15
Health Status: unhealthy
Condition: Vision Impairment
Age Group: child|adult
Population Size: 15
Sources:
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Metoclopramide and pimozide in Parkinson's disease and levodopa-induced dyskinesias.
1975 Apr
The effects of combining carbidopa with levodopa for Parkinson's disease.
1975 Dec
Levodopa-induced postural hypotension. Treatment with fludrocortisone.
1975 Jan
[Abnormal movements induced by L-dopa. New therapeutic possibilities].
1975 Jan 25
Persistent parkinsonism following neuroleptanalgesia.
1975 May
Reduction of dyskinesia and induction of akinesia induced by morphine in two parkinsonian patients with severe sciatica.
1999
Functional mapping of the human globus pallidus: contrasting effect of stimulation in the internal and external pallidum in Parkinson's disease.
2000
[Amantadine for the treatment of levodopa dyskinesias in Parkinson's disease].
2000
[Dopaminergic agonists in the treatment of Parkinson's disease].
2000 Dec
Evidence of functional somatotopy in GPi from results of pallidotomy.
2000 Dec
Effect of subthalamic nucleus stimulation on levodopa-induced dyskinesia in Parkinson's disease.
2000 Dec 26
Four novel mutations in the tyrosine hydroxylase gene in patients with infantile parkinsonism.
2000 Jan
L-Dopa uptake and dopamine production in proximal tubular cells are regulated by beta(2)-adrenergic receptors.
2000 Jul
[Worsened orthostatic hypotension due to levodopa administration in a case of Parkinson's disease].
2000 Mar
Detection and assessment of the severity of levodopa-induced dyskinesia in patients with Parkinson's disease by neural networks.
2000 Nov
Centrally initiated postural adjustments in parkinsonian patients on and off levodopa.
2000 Nov
[Treatment of advanced Parkinson's disease].
2000 Oct
Expression of metallothionein-III mRNA and its regulation by levodopa in the basal ganglia of hemi-parkinsonian rats.
2000 Oct 20
The 4F2hc/LAT1 complex transports L-DOPA across the blood-brain barrier.
2000 Oct 6
Workshop IV: drug treatment guidelines for the long-term management of Parkinson's disease.
2000 Sep
Beneficial effects of amantadine on L-dopa-induced dyskinesias in Parkinson's disease.
2000 Sep
Pathologic gambling in Parkinson's disease: a behavioral manifestation of pharmacologic treatment?
2000 Sep
Adverse drug reactions to selegiline: a review of the French pharmacovigilance database.
2000 Sep-Oct
Inhibition of potato polyphenol oxidase by anions and activity in various carboxylate buffers (pH 4.8) at constant ionic strength.
2001
A study of excessive daytime sleepiness and its clinical significance in three groups of Parkinson's disease patients taking pramipexole, cabergoline and levodopa mono and combination therapy.
2001
Efficacy and tolerability of entacapone as adjunctive therapy to levodopa in patients with Parkinson's disease and end-of-dose deterioration in daily medical practice: an open, multicenter study.
2001
Selective dopaminergic vulnerability: 3,4-dihydroxyphenylacetaldehyde targets mitochondria.
2001 Apr 15
Dimeric L-dopa derivatives as potential prodrugs.
2001 Apr 23
SCH 58261, an A(2A) adenosine receptor antagonist, counteracts parkinsonian-like muscle rigidity in rats.
2001 Aug
Dopamine D(2) receptors regulate tyrosine hydroxylase activity and phosphorylation at Ser40 in rat striatum.
2001 Feb
Induction by dopamine D1 receptor agonist ABT-431 of dyskinesia similar to levodopa in patients with Parkinson disease.
2001 Feb
Molecular mechanisms controlling the rate and specificity of catechol O-methylation by human soluble catechol O-methyltransferase.
2001 Feb
Accelerometric assessment of levodopa-induced dyskinesias in Parkinson's disease.
2001 Jan
SPECT imaging of the dopamine transporter in juvenile-onset dystonia.
2001 Jan 23
Enhanced abilities of highly swollen chitosan beads for color removal and tyrosinase immobilization.
2001 Jan 29
Biogenic aldehyde(s) derived from the action of monoamine oxidase may mediate the antidipsotropic effect of daidzin.
2001 Jan 30
Role of peroxynitrite in macrophage microbicidal mechanisms in vivo revealed by protein nitration and hydroxylation.
2001 Jun 1
Resveratrol and a novel tyrosinase in Carignan grape juice.
2001 Mar
Does stimulation of the GPi control dyskinesia by activating inhibitory axons?
2001 Mar
Effects of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) on alpha2-adrenoceptors which regulate the synthesis and release of noradrenaline in the rat brain.
2001 Mar
Event-related functional magnetic resonance imaging in Parkinson's disease before and after levodopa.
2001 Mar
Comparative analysis of the gait disorder of normal pressure hydrocephalus and Parkinson's disease.
2001 Mar
The effect of levodopa on vocal function in Parkinson's disease.
2001 Mar-Apr
Levodopa-induced drowsiness in healthy volunteers: results of a choice reaction time test combined with a subjective evaluation of sedation.
2001 Mar-Apr
Parkinsonism after glycine-derivate exposure.
2001 May
Speech dysfluency exacerbated by levodopa in Parkinson's disease.
2001 May
Intravenous amantadine improves levadopa-induced dyskinesias: an acute double-blind placebo-controlled study.
2001 May
Chromium(VI) reduction by catechol(amine)s results in DNA cleavage in vitro: relevance to chromium genotoxicity.
2001 May
Coadministration of (-)-OSU6162 with l-DOPA normalizes preproenkephalin mRNA expression in the sensorimotor striatum of primates with unilateral 6-OHDA lesions.
2001 May
Biperiden enhances L-DOPA methyl ester and dopamine D(l) receptor agonist SKF-82958 but antagonizes D(2)/D(3) receptor agonist rotigotine antihemiparkinsonian actions.
2008 Dec 3
Patents

Sample Use Guides

Maximum dosage in a 24-hour period is eight tablets (Stalevo 50, containing 12.5 mg of carbidopa, 50 mg of levodopa and 200 mg of entacapone; Stalevo 75, containing 18.75 mg of carbidopa, 75 mg of levodopa and 200 mg of entacapone; Stalevo 100, containing 25 mg of carbidopa, 100 mg of levodopa and 200 mg of entacapone; Stalevo 125, containing 31.25 mg of carbidopa, 125 mg of levodopa and 200 mg of entacapone; Stalevo 150, containing 37.5 mg of carbidopa, 150 mg of levodopa and 200 mg of entacapone; Stalevo 200, containing 50 mg of carbidopa, 200 mg of levodopa and 200 mg of entacapone). The optimum daily dosage must be determined by careful titration in each patient.
Route of Administration: Oral
Low dose (<30 uM) Levodopa protects PC12 cells against oxidative stress which might be related to the up-regulation of CD39 and pCREB expression.
Name Type Language
MELEVODOPA
INN   WHO-DD  
INN  
Official Name English
CHF-1301
Code English
(-)-3,4-DIHYDROXY-L-PHENYLALANINE, METHYL ESTER
Common Name English
Melevodopa [WHO-DD]
Common Name English
melevodopa [INN]
Common Name English
LEVOMET
Brand Name English
Classification Tree Code System Code
WHO-VATC QN04BA04
Created by admin on Fri Dec 15 16:46:28 GMT 2023 , Edited by admin on Fri Dec 15 16:46:28 GMT 2023
WHO-VATC QN04BA05
Created by admin on Fri Dec 15 16:46:28 GMT 2023 , Edited by admin on Fri Dec 15 16:46:28 GMT 2023
NCI_THESAURUS C66884
Created by admin on Fri Dec 15 16:46:28 GMT 2023 , Edited by admin on Fri Dec 15 16:46:28 GMT 2023
WHO-ATC N04BA05
Created by admin on Fri Dec 15 16:46:28 GMT 2023 , Edited by admin on Fri Dec 15 16:46:28 GMT 2023
WHO-ATC N04BA04
Created by admin on Fri Dec 15 16:46:28 GMT 2023 , Edited by admin on Fri Dec 15 16:46:28 GMT 2023
Code System Code Type Description
EPA CompTox
DTXSID9048433
Created by admin on Fri Dec 15 16:46:28 GMT 2023 , Edited by admin on Fri Dec 15 16:46:28 GMT 2023
PRIMARY
DRUG BANK
DB13313
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EVMPD
SUB32447
Created by admin on Fri Dec 15 16:46:28 GMT 2023 , Edited by admin on Fri Dec 15 16:46:28 GMT 2023
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WIKIPEDIA
Melevodopa
Created by admin on Fri Dec 15 16:46:28 GMT 2023 , Edited by admin on Fri Dec 15 16:46:28 GMT 2023
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FDA UNII
M30686U4X4
Created by admin on Fri Dec 15 16:46:28 GMT 2023 , Edited by admin on Fri Dec 15 16:46:28 GMT 2023
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CAS
7101-51-1
Created by admin on Fri Dec 15 16:46:28 GMT 2023 , Edited by admin on Fri Dec 15 16:46:28 GMT 2023
PRIMARY
NCI_THESAURUS
C83927
Created by admin on Fri Dec 15 16:46:28 GMT 2023 , Edited by admin on Fri Dec 15 16:46:28 GMT 2023
PRIMARY
ChEMBL
CHEMBL1328898
Created by admin on Fri Dec 15 16:46:28 GMT 2023 , Edited by admin on Fri Dec 15 16:46:28 GMT 2023
PRIMARY
DRUG CENTRAL
1673
Created by admin on Fri Dec 15 16:46:28 GMT 2023 , Edited by admin on Fri Dec 15 16:46:28 GMT 2023
PRIMARY
PUBCHEM
23497
Created by admin on Fri Dec 15 16:46:28 GMT 2023 , Edited by admin on Fri Dec 15 16:46:28 GMT 2023
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INN
7973
Created by admin on Fri Dec 15 16:46:28 GMT 2023 , Edited by admin on Fri Dec 15 16:46:28 GMT 2023
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MESH
C035420
Created by admin on Fri Dec 15 16:46:28 GMT 2023 , Edited by admin on Fri Dec 15 16:46:28 GMT 2023
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SMS_ID
100000124311
Created by admin on Fri Dec 15 16:46:28 GMT 2023 , Edited by admin on Fri Dec 15 16:46:28 GMT 2023
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