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Details

Stereochemistry ABSOLUTE
Molecular Formula C9H12NO7P
Molecular Weight 277.1682
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of FOSLEVODOPA

SMILES

c1cc(c(cc1C[C@@]([H])(C(=O)O)N)O)OP(=O)(O)O

InChI

InChIKey=YNDMEEULGSTYJT-LURJTMIESA-N
InChI=1S/C9H12NO7P/c10-6(9(12)13)3-5-1-2-8(7(11)4-5)17-18(14,15)16/h1-2,4,6,11H,3,10H2,(H,12,13)(H2,14,15,16)/t6-/m0/s1

HIDE SMILES / InChI

Molecular Formula C9H12NO7P
Molecular Weight 277.1682
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment:: 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

1055203200000
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
Health Status: unhealthy
Age Group: 54 years
Sex: F
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
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
Health Status: unhealthy
Age Group: child|adult
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
Health Status: unhealthy
Age Group: child|adult
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
Health Status: unhealthy
Age Group: 54 years
Sex: F
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
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
Health Status: unhealthy
Age Group: child|adult
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
Health Status: unhealthy
Age Group: child|adult
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
Health Status: unhealthy
Age Group: child|adult
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
Health Status: unhealthy
Age Group: child|adult
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
Health Status: unhealthy
Age Group: child|adult
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
Health Status: unhealthy
Age Group: child|adult
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
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
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
Apomorphine: an underutilized therapy for Parkinson's disease.
2000 Sep
Adverse drug reactions to selegiline: a review of the French pharmacovigilance database.
2000 Sep-Oct
Pharmacokinetic-pharmacodynamic relationship of levodopa with and without tolcapone in patients with Parkinson's disease.
2001
Melanogenesis by tyrosinase action on 3,4-dihydroxyphenylalanine (DOPA) in the presence of polyethylene glycol: a matrix-assisted laser desorption/ionization mass spectrometric investigation.
2001
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
High dose naltrexone for dyskinesias induced by levodopa.
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
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
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 Jun 25 21:43:29 UTC 2021
Edited
by admin
on Fri Jun 25 21:43:29 UTC 2021
Record UNII
37NQZ0J76I
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
FOSLEVODOPA
INN   USAN  
Official Name English
FOSLEVODOPA [USAN]
Common Name English
3-HYDROXY-O-PHOSPHONO-L-TYROSINE
Common Name English
L-TYROSINE, 3-HYDROXY-O-PHOSPHONO-
Common Name English
ABBV-951 COMPONENT FOSLEVODOPA
Code English
L-TYROSINE, 3-HYDROXY-, 4-(DIHYDROGEN PHOSPHATE)
Systematic Name English
FOSLEVODOPA [INN]
Common Name English
LEVODOPA-4'-MONOPHOSPHATE
Common Name English
Code System Code Type Description
CAS
97321-87-4
Created by admin on Fri Jun 25 21:43:29 UTC 2021 , Edited by admin on Fri Jun 25 21:43:29 UTC 2021
PRIMARY
FDA UNII
37NQZ0J76I
Created by admin on Fri Jun 25 21:43:29 UTC 2021 , Edited by admin on Fri Jun 25 21:43:29 UTC 2021
PRIMARY
INN
11006
Created by admin on Fri Jun 25 21:43:29 UTC 2021 , Edited by admin on Fri Jun 25 21:43:29 UTC 2021
PRIMARY
PUBCHEM
127766
Created by admin on Fri Jun 25 21:43:29 UTC 2021 , Edited by admin on Fri Jun 25 21:43:29 UTC 2021
PRIMARY
NCI_THESAURUS
C166651
Created by admin on Fri Jun 25 21:43:29 UTC 2021 , Edited by admin on Fri Jun 25 21:43:29 UTC 2021
PRIMARY
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