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Details

Stereochemistry ABSOLUTE
Molecular Formula C10H13NO4.ClH
Molecular Weight 247.675
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of MELEVODOPA HYDROCHLORIDE

SMILES

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

InChI

InChIKey=WFGNJLMSYIJWII-FJXQXJEOSA-N
InChI=1S/C10H13NO4.ClH/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;1H/t7-;/m0./s1

HIDE SMILES / InChI

Molecular Formula C10H13NO4
Molecular Weight 211.2145
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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
Levodopa-induced postural hypotension. Treatment with fludrocortisone.
1975 Jan
Persistent parkinsonism following neuroleptanalgesia.
1975 May
Levodopa-induced myoclonus.
1975 May
Risk factors for levodopa-induced dyskinesias in Parkinson's disease.
1999 Dec
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
Effects of oligonucleotide antisense to dopamine D(1A) receptor messenger RNA in a rodent model of levodopa-induced dyskinesia.
2000
Tolcapone increases maximum concentration of levodopa.
2000
Preventing levodopa-induced dyskinesias.
2000 Apr
Investigating levodopa-induced dyskinesias in the parkinsonian primate.
2000 Apr
Bilateral subthalamic stimulation for Parkinson's disease by using three-dimensional stereotactic magnetic resonance imaging and electrophysiological guidance.
2000 Apr
Quetiapine for l-dopa-induced psychosis in PD.
2000 Apr 11
Sleep attacks and Parkinson's disease treatment.
2000 Apr 15
AMPA receptor blockade improves levodopa-induced dyskinesia in MPTP monkeys.
2000 Apr 25
[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
Association study of dopamine receptor gene polymorphisms with drug-induced hallucinations in patients with idiopathic Parkinson's disease.
2000 Feb
L-Dopa uptake and dopamine production in proximal tubular cells are regulated by beta(2)-adrenergic receptors.
2000 Jul
Embryonic ventral mesencephalic grafts improve levodopa-induced dyskinesia in a rat model of Parkinson's disease.
2000 Jul
[Worsened orthostatic hypotension due to levodopa administration in a case of Parkinson's disease].
2000 Mar
Levodopa-induced dyskinesias in autopsy-proven cortical-basal ganglionic degeneration.
2000 Mar
Idazoxan is ineffective for levodopa-induced dyskinesias in Parkinson's disease.
2000 Mar
The effect of amantadine on levodopa-induced dyskinesias in Parkinson's disease: a double-blind, placebo-controlled study.
2000 Mar-Apr
Relationship among nigrostriatal denervation, parkinsonism, and dyskinesias in the MPTP primate model.
2000 May
Levodopa-induced dyskinesias in Parkinson's disease: is sensitization reversible?
2000 May
[Treatment of advanced Parkinson's disease].
2000 Oct
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
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
Localization of a novel locus for autosomal recessive early-onset parkinsonism, PARK6, on human chromosome 1p35-p36.
2001 Apr
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
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
Resveratrol and a novel tyrosinase in Carignan grape juice.
2001 Mar
Does stimulation of the GPi control dyskinesia by activating inhibitory axons?
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
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
Chromium(VI) reduction by catechol(amine)s results in DNA cleavage in vitro: relevance to chromium genotoxicity.
2001 May
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.
Substance Class Chemical
Created
by admin
on Fri Dec 15 18:50:30 GMT 2023
Edited
by admin
on Fri Dec 15 18:50:30 GMT 2023
Record UNII
JFU1A8866V
Record Status Validated (UNII)
Record Version
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Name Type Language
MELEVODOPA HYDROCHLORIDE
Common Name English
NSC-295453
Code English
L-DOPA METHYL ESTER HYDROCHLORIDE
Common Name English
ALANINE, 3-(3,4-DIHYDROXYPHENYL)-, METHYL ESTER, HYDROCHLORIDE
Common Name English
L-TYROSINE, 3-HYDROXY-, METHYL ESTER, HYDROCHLORIDE
Common Name English
ST-41769
Code English
LEVODOPA METHYL ESTER HYDROCHLORIDE
Common Name English
ST 41769
Code English
L-DOPA ME ESTER HYDROCHLORIDE
Common Name English
L-TYROSINE, 3-HYDROXY-, METHYL ESTER, HYDROCHLORIDE (1:1)
Common Name English
METHYL L-3-(3,4-DIHYDROXYPHENYL)ALANINATE HYDROCHLORIDE
Common Name English
ALANINE, 3-(3,4-DIHYDROXYPHENYL)-, METHYL ESTER, HYDROCHLORIDE, L-
Common Name English
3,4-DIHYDROXYPHENYL-L-ALANINE METHYL ESTER HYDROCHLORIDE
Systematic Name English
Code System Code Type Description
FDA UNII
JFU1A8866V
Created by admin on Fri Dec 15 18:50:30 GMT 2023 , Edited by admin on Fri Dec 15 18:50:30 GMT 2023
PRIMARY
EPA CompTox
DTXSID4045763
Created by admin on Fri Dec 15 18:50:30 GMT 2023 , Edited by admin on Fri Dec 15 18:50:30 GMT 2023
PRIMARY
CAS
1421-65-4
Created by admin on Fri Dec 15 18:50:30 GMT 2023 , Edited by admin on Fri Dec 15 18:50:30 GMT 2023
PRIMARY
PUBCHEM
10131132
Created by admin on Fri Dec 15 18:50:30 GMT 2023 , Edited by admin on Fri Dec 15 18:50:30 GMT 2023
PRIMARY
NSC
295453
Created by admin on Fri Dec 15 18:50:30 GMT 2023 , Edited by admin on Fri Dec 15 18:50:30 GMT 2023
PRIMARY
MESH
C035420
Created by admin on Fri Dec 15 18:50:30 GMT 2023 , Edited by admin on Fri Dec 15 18:50:30 GMT 2023
PRIMARY
EVMPD
SUB33439
Created by admin on Fri Dec 15 18:50:30 GMT 2023 , Edited by admin on Fri Dec 15 18:50:30 GMT 2023
PRIMARY
SMS_ID
100000127428
Created by admin on Fri Dec 15 18:50:30 GMT 2023 , Edited by admin on Fri Dec 15 18:50:30 GMT 2023
PRIMARY
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