Page last updated: 2024-11-04

dihydroxyphenylalanine

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Description

Dihydroxyphenylalanine: A beta-hydroxylated derivative of phenylalanine. The D-form of dihydroxyphenylalanine has less physiologic activity than the L-form and is commonly used experimentally to determine whether the pharmacological effects of LEVODOPA are stereospecific. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

dopa : A hydroxyphenylalanine carrying hydroxy substituents at positions 3 and 4 of the benzene ring. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Cross-References

ID SourceID
PubMed CID836
CHEMBL ID351042
CHEBI ID49168
SCHEMBL ID24360
MeSH IDM0006754

Synonyms (110)

Synonym
AKOS001132704
bdbm4377
2-amino-3-(3,4-dihydroxy-phenyl)-propionic acid
3(3,4-dihydroxyphenyl)dl-alanine
2-amino-3-(3,4-dihydroxyphenyl)propanoic acid
dl-alanine, 3-(3,4-dihydroxy-phenyl)-
D9503
nsc 16940
einecs 200-566-0
ai3-23874
alanine, 3-(3,4-dihydroxyphenyl)-, dl-
IM3 ,
(.+-.)-dopa
(.+-.)-3,4-dihydroxyphenylalanine
3-(3,4-dihydroxyphenyl)-dl-alanine
nsc16940
63-84-3
wln: qvyz1r cq dq
3,4-dihydroxy-dl-phenylalanine
.beta.-(3,4-dihydroxyphenyl)-dl-.alpha.-alanine
dl-tyrosine, 3-hydroxy-
dl-3,4-dopa
dl-dopa
dl-dioxyphenylalanine
(.+-.)-3-(3,4-dihydroxyphenyl)alanine
dl-.beta.-(3,4-dihydroxyphenyl)alanine
nsc-16940
dl-dihydroxyphenylalanine
alanine,4-dihydroxyphenyl)-, dl-
3',4'-dihydroxyphenylalanine
dl-3,4-dihydroxyphenylalanine
nsc-118368
nsc118368
d-tyrosine, 3-hydroxy-
alanine,4-dihydroxyphenyl)-, d-
d-b-3,4-dihydroxyphenylalanine
(r,s)-dopa
3-hydroxy-dl-tyrosine
(+-)-dopa
beta-(3,4-dihydroxyphenyl)-dl-alpha-alanine
dl-beta-(3,4-dihydroxyphenyl)alanine
dl-beta-(3,4-dihydroxyphenyl)-alpha-alanine
(+-)-3-(3,4-dihydroxyphenyl)alanine
CHEBI:49168 ,
beta-(3,4-dihydroxyphenyl)-alpha-alanine
dopa
dihydroxyphenylalanine
3-hydroxytyrosine
NCGC00095195-01
NCGC00095195-02
DD916368-6635-446F-AF55-7B416FD65026
D0599
L001274
FT-0695064
FT-0667771
FT-0650636
CHEMBL351042
STK801445
A834552
BBL010087
alanine, 3-(3,4-dihydroxyphenyl)-, d-
NCGC00015384-02
NCGC00015384-03
qi9c343r60 ,
unii-qi9c343r60
tyrosine, 3-hydroxy-
BP-12841
d-3-hydroxytyrosine
3-(3,4-dihydroxyphenyl)-d-alanine
587-45-1
FT-0603250
dl-3-hydroxytyrosine
SCHEMBL24360
(+/-)-3,4-dihydroxyphenylalanine
dopa dl-form
dopa, dl-
dopa dl-form [mi]
AKOS016843592
3,4-dihydroxyphenylalanine #
mfcd00063061
mfcd00063060
mfcd00002598
DTXSID8020549
GS-6861
3,4-dihydroxy-dl-phenylalanine, 97%
a-amino-3,4-dihydroxy-benzenepropanoate
alpha-amino-3,4-dihydroxy-benzenepropanoate
(+/-) 3-(3,4-dihydroxyphenyl)alanine
alpha-amino-hydrocaffeic acid
dl-b-(3,4-dihydroxyphenyl)alanine
2-amino-3-(3,4-dihydroxyphenyl)propanoate
b-(3,4-dihydroxyphenyl)-a-alanine
a-amino-3,4-dihydroxy-benzenepropanoic acid
dl-3',4'-dihydroxyphenylalanine
alpha-amino-3,4-dihydroxy-benzenepropanoic acid
dl-4,5-dihydroxyphenylalanine
HY-113404
CS-0059346
S6083
l-dopa; 3,4-dihydroxy-l-phenylalanine
BCP25747
Q27121510
(2-pyrrolidin-3-yl-ethyl)-carbamic acid benzyl ester
FT-0775213
H11952
SY010977
PB43103
EN300-52489
AS-81574
SY343921

Research Excerpts

Overview

3,4-Dihydroxyphenylalanine (DOPA) is an amino acid found in the biosynthesis of catecholamines in animals and plants. It is a neutral amino acid that resembles natural L-dopa (dopamine precursor)

ExcerptReferenceRelevance
"3,4-Dihydroxyphenylalanine (Dopa) is a versatile molecule that enables marine mussels to achieve successful underwater adhesion. "( Thiol-Rich fp-6 Controls the Tautomer Equilibrium of Oxidized Dopa in Interfacial Mussel Foot Proteins.
Cha, HJ; Shin, M; Yang, B; Yoon, T, 2022
)
1.28
"L-dihydroxyphenylalanine (DOPA) is an amino acid found in the biosynthesis of catecholamines in animals and plants. "( Genetic Incorporation of Biosynthesized L-dihydroxyphenylalanine (DOPA) and Its Application to Protein Conjugation.
Kim, S; Lee, HS, 2018
)
1.47
"Dihydroxyphenylalanine (DOPA) is a neutral amino acid that resembles natural L-dopa (dopamine precursor). "( Normal biodistribution pattern and physiologic variants of 18F-DOPA PET imaging.
Al-Nahhas, A; Chondrogiannis, S; Marzola, MC; Mazza, A; Opocher, G; Rubello, D; Venkatanarayana, TD, 2013
)
1.83
"3,4-Dihydroxyphenylalanine (DOPA) is an amino acid that occurs naturally in the primary sequence of many proteins and peptides. "( Detection of peptidyl-3,4-dihydroxyphenylalanine by amino acid analysis and microsequencing techniques.
Waite, JH, 1991
)
1.14

Toxicity

ExcerptReferenceRelevance
" Solutions of TOPA were also toxic to mesencephalic neurons after acute or chronic exposure, displaying the same leftward shift in LD50."( Characterization of 2,4,5-trihydroxyphenylalanine neurotoxicity in vitro and protective effects of ganglioside GM1: implications for Parkinson's disease.
Dal Toso, R; Facci, L; Leon, A; Moroni, F; Schiavo, N; Skaper, SD; Vantini, G, 1992
)
0.28
" In addition, 2 mM GSH protected neurons from the toxic effects of 200 microM TOPA, but was not effective against 200 microM NMDA."( Glutathione prevents 2,4,5-trihydroxyphenylalanine excitotoxicity by maintaining it in a reduced, non-active form.
Aizenman, E; Boeckman, FA; Rosenberg, PA, 1992
)
0.28
" Triphenols and o- and p-diphenols underwent complete oxidation in culture medium within 24 h of incubation and were significantly more toxic than monophenols and the m-diphenol resorcinol, which, under the same cultural conditions, were much more stable."( Comparative cytotoxicity of phenols in vitro.
Nazzaro-Porro, M; Passi, S; Picardo, M, 1987
)
0.27
" Dopa-melanin and medium containing decomposed dopa were also selectively toxic to MM96 cells."( Modification of dopa toxicity in human tumour cells.
Parsons, PG, 1985
)
0.27
" We found that under the usual conditions of the biological assay, the apparent cytotoxicity of the two indoles reflect their instability in the culture medium, the less stable DHI being generally more toxic than DHICA to melanoma cells and nonmelanocytic cells."( The inherent cytotoxicity of melanin precursors: a revision.
Aroca, P; Hearing, VJ; Mascagna, D; Palumbo, A; Prota, G; Tsukamoto, K; Urabe, K, 1994
)
0.29
" Moreover, both drugs killed THir as well as non-THir cells at high concentrations, suggesting a nonspecific toxic effect."( Comparison of the neurotoxicity of dihydroxyphenylalanine stereoisomers in cultured dopamine neurons.
Carvey, PM; Ling, ZD; Pieri, SC, 1996
)
0.57
" Benzoquinone was typically significantly more toxic than hydroquinone, while 1,2-naphthoquinone was typically significantly more toxic than 1,2-dihydroxynaphthalene."( Comparative toxicity of allelochemicals and their enzymatic oxidation products to maize fungal pathogens, emphasizing Fusarium graminearum.
Dowd, PF; Duvick, JP; Rood, T, 1997
)
0.3
" Overall, these results suggest that, at least in 1-year-old mice, dietary restriction for 3 months does not protect nigral DA nerve terminals from low toxic dosages of MPTP."( Dietary restriction does not protect the nigrostriatal dopaminergic pathway of older animals from low-dose MPTP-induced neurotoxicity.
Morgan, WW; Nelson, JF; Richardson, AG, 2003
)
0.32
" The antiarrhythmics studied cause adverse reactions to the eye."( Interaction of quinidine, disopyramide and metoprolol with melanin in vitro in relation to drug-induced ocular toxicity.
Buszman, E; Rózańska, R, 2003
)
0.32
"The aim of this study was to examine in vitro the interaction between aminoglycoside antibiotics displaying adverse ototoxic effects and melanin which is a constituent of the inner ear."( Interaction of neomycin, tobramycin and amikacin with melanin in vitro in relation to aminoglycosides-induced ototoxicity.
Buszman, E; Trzcionka, J; Wrześniok, D, 2007
)
0.34
" Except for growth deceleration at a higher dosage, no significant adverse effects were noted."( Efficacy and safety of long-term, continuous subcutaneous octreotide infusion for patients with different subtypes of KATP-channel hyperinsulinism.
Aizu, K; Fujimaru, R; Hosokawa, Y; Kawakita, R; Masue, M; Matsubara, K; Nagasaka, H; Nishibori, H; Suzuki, S; Yorifuji, T, 2013
)
0.39
" Safety evaluation included haematology, biochemistry, urinalysis parameters and adverse event monitoring."( Efficacy and safety of standardized extract of Trigonella foenum-graecum L seeds as an adjuvant to L-Dopa in the management of patients with Parkinson's disease.
Joshi, V; Mohan, V; Nathan, J; Panjwani, S; Thakurdesai, PA, 2014
)
0.4

Pharmacokinetics

ExcerptReferenceRelevance
" route, elimination followed apparent first order kinetics and was biphasic with a t 1/2 alpha of 7 min and terminal half-life of 67 min."( Pharmacokinetics, bioavailability, metabolism, tissue distribution and urinary excretion of gamma-L-glutamyl-L-dopa in the rat.
Cummings, J; Matheson, LM; Maurice, L; Smyth, JF, 1990
)
0.28
" The mean residence time and half-life were 20."( The pharmacokinetics of gamma-glutamyl-L-dopa in normal and anephric rats and rats with glycerol-induced acute renal failure.
Barber, HE; Boateng, YA; Lee, MR; MacDonald, TM; Petrie, JC; Whiting, PH, 1990
)
0.28
" 163) on the serum t1/2 and other pharmacokinetic parameters of co-administered L-3,4-dihydroxyphenylalanine (L-DOPA) were compared to those of the reversible inhibitor, carbidopa in rats."( A comparison of the effects of reversible and irreversible inhibitors of aromatic L-amino acid decarboxylase on the half-life and other pharmacokinetic parameters of oral L-3,4-dihydroxyphenylalanine.
Haegele, KD; Huebert, ND; Palfreyman, MG,
)
0.55
" The peak levodopa concentration (Cmax) and the area under the time-concentration curve (AUC) were markedly increased after long-term levodopa therapy, whereas the time to the peak concentration (Tmax) and the elimination half-life (T(1/2)) were decreased."( Effects of chronic levodopa therapy on dopa pharmacokinetics.
Kanazawa, I; Murata, M, 1997
)
0.3
"Parkinsonian patients in early stages of the disease have a pharmacokinetic pattern of free L-dopa similar to that of healthy subjects."( Human pharmacokinetics of L-3,4-dihydroxyphenylalanine studied with microdialysis.
Dizdar, N; Kagedal, B; Kullman, A; Norlander, B; Olsson, JE, 1999
)
0.59
" Study of pharmacokinetic parameters (AUC, C(max), and T(max)) revealed a greater and more extended release of ropinirole from nanoemulsion gel compared to that from a conventional gel (RPG) and oral marketed tablet (Ropitor)."( Oil based nanocarrier system for transdermal delivery of ropinirole: a mechanistic, pharmacokinetic and biochemical investigation.
Ahmad, FJ; Azeem, A; Iqbal, Z; Khar, RK; Negi, LM; Talegaonkar, S, 2012
)
0.38
" Changes of small magnitude but with possible clinical impact were found according to tmax and Cmax that tended to be lower in HP- patients and AUC0-t that was larger in the HP+ group."( Pharmacokinetics of levodopa in patients with Parkinson disease and motor fluctuations depending on the presence of Helicobacter pylori infection.
Adamiak-Giera, U; Białecka, M; Gawrońska-Szklarz, B; Madaliński, MH; Narożańska, E; Robowski, P; Schinwelski, M; Sołtan, W; Sławek, J,
)
0.13

Compound-Compound Interactions

ExcerptReferenceRelevance
"Thirty patients with Parkinson's disease were treated for four weeks with levodopa combined with an inhibitor of extracerebral dopa decarboxylase, L-alpha-methyldopahydrazine (MK 486)."( Treatment of Parkinson's disease with levodopa combined with L-alpha-methyldopahydrazine, an inhibitor of extracerebral DOPA decarboxylase.
Barry, PE; Marsden, CD; Parkes, JD; Zilkha, KJ, 1973
)
0.25
"The clinical actions of levodopa in Parkinsonism, given with and without an extracerebral decarboxylase in hibitor, L-alpha-methyldopahydrazine, were compared."( Idiopathic Parkinsonism treated with an extracerebral decarboxylase inhibitor in combination with levodopa.
Calne, DB; Gawler, J; Hilson, A; Pallis, CA; Petrie, A; Rao, S; Reid, JL; Thomas, PK; Vakil, SD, 1971
)
0.25
"In order to demonstrate the existence of proliferating activity in hair follicular melanocytes during the early and anagen III stages, immunocytochemistry for bromodeoxyuridine (BrdU) incorporated in the nuclei of the melanocytes for 1 hr was undertaken at the light and electron microscopic levels in combination with DOPA reaction cytochemistry."( Proliferating activity of the hair follicular melanocytes at the early and anagen III stages in the hair growth cycle: detection by immunocytochemistry for bromodeoxyuridine combined with DOPA reaction cytochemistry.
Morimoto, Y; Saga, K; Sugiyama, S; Takahashi, M, 1995
)
0.29
" The aim of this article is to show the first case of focal CHI diagnosed in Spain using PET-CT imaging combined with genetic analysis."( [18F-fluoro-L-DOPA PET-CT imaging combined with genetic analysis for optimal classification and treatment in a child with severe congenital hyperinsulinism].
Arbizu Lostao, J; Azcona San Julián, C; Carracedo, A; Fernández-Marmiesse, A; Garrastachu Zumarrán, P; Martino Casado, E; Richter Echevarría, JA, 2008
)
0.35

Bioavailability

ExcerptReferenceRelevance
" The simplicity, sensitivity, and accuracy of this method make it suitable for routine clinical analysis of serum samples to optimize bioavailability for individual patients."( Liquid chromatographic method for monitoring therapeutic concentrations of L-dopa and dopamine in serum.
Alcorn, RL; Kissinger, PT; Riggin, RM, 1976
)
0.26
" dosing (65 min), and bioavailability was 40%."( Pharmacokinetics, bioavailability, metabolism, tissue distribution and urinary excretion of gamma-L-glutamyl-L-dopa in the rat.
Cummings, J; Matheson, LM; Maurice, L; Smyth, JF, 1990
)
0.28
" In a second study the oral bioavailability of gludopa was estimated in normal subjects and found to be low (less than 2%)."( Effect of prolonged intravenous infusion of gludopa in humans and a preliminary study of its oral bioavailability.
Ellis, R; Freestone, S; Lee, MR; MacDonald, TM, 1990
)
0.28
" The increase in FDOPA bioavailability to the brain resulted in greater selective FDA accumulation in striatum."( The effects of carbidopa on the metabolism of 6-[18F]fluoro-L-dopa in rats, monkeys and humans.
Barrio, JR; Hoffman, JM; Luxen, A; Melega, WP; Nissenson, CH; Phelps, ME, 1990
)
0.28
" The oral bioavailability of gludopa is only 1 to 2% and this rules out the dipeptide as an effective dopaminergic prodrug."( Five years' experience with gamma-L-glutamyl-L-dopa: a relatively renally specific dopaminergic prodrug in man.
Lee, MR, 1990
)
0.28
" In addition, L-654,284 had better (5-6 times) oral bioavailability than RX 781094 or WY 26703."( L-654,284 a new potent and selective alpha 2-adrenoceptor antagonist.
Baldwin, JJ; Clineschmidt, BV; Huff, JR; Lotti, VJ; Martin, GE; Pettibone, DJ; Randall, WC; Vacca, J, 1986
)
0.27
"The effect of doubling carbidopa intake on single dose bioavailability of L-Dopa was examined in five parkinsonian patients."( Effect of supplemental carbidopa on bioavailability of L-dopa.
Cedarbaum, JM; Dhar, AK; Kutt, H; McDowell, FH; Watkins, S, 1986
)
0.27
" 163, administered as their DL-racemic mixtures, produced increases in the t1/2 and bioavailability of co-administered L-DOPA comparable to that produced by a 10-fold larger dose of carbidopa administered as the active L-enantiomer; increasing the dose of MDL 72."( A comparison of the effects of reversible and irreversible inhibitors of aromatic L-amino acid decarboxylase on the half-life and other pharmacokinetic parameters of oral L-3,4-dihydroxyphenylalanine.
Haegele, KD; Huebert, ND; Palfreyman, MG,
)
0.32
"To investigate the relation between "on-off" fluctuations in symptomatology and bioavailability of dopa in patients with Parkinson's disease, five Parkinsonian patients with pronounced "on-off" symptoms were studied."( "On-off" phenomenon in Parkinson's disease: correlation to the concentration of dopa in plasma.
Carlsson, A; Eriksson, T; Granérus, AK; Linde, A; Magnusson, T, 1984
)
0.27
"In 6-[18F]fluoro-L-dopa (Fdopa)/positron emission tomography (PET) studies, carbidopa pretreatment increases the Fdopa bioavailability to the brain and enhances the intensity of striatal PET images."( Routes of administration and effect of carbidopa pretreatment on 6-[18F]fluoro-L-dopa/PET scans in non-human primates.
Chan, GL; Dobko, T; Doudet, DJ; Hewitt, KA; Pate, BD; Ruth, TJ; Schofield, P, 1995
)
0.29
" In animal studies, these compounds inhibit effectively the O-methylation of L-dopa, thus improving its bioavailability and brain penetration and potentiating its behavioural effects."( General properties and clinical possibilities of new selective inhibitors of catechol O-methyltransferase.
Gordin, A; Kaakkola, S; Männistö, PT, 1994
)
0.29
" In conclusion, the novel COMT inhibitor BIA 3-202 was well tolerated and significantly increased the bioavailability of levodopa and reduced the formation of 3-OMD when administered with standard release levodopa/benserazide."( Pharmacokinetic-pharmacodynamic interaction between BIA 3-202, a novel COMT inhibitor, and levodopa/benserazide.
Almeida, L; Falcão, A; Loureiro, A; Machado, R; Maia, J; Silveira, P; Soares-da-Silva, P; Torrão, L; Vaz-da-Silva, M; Wright, L, 2003
)
0.32
" Long-term levodopa administration results in an increased levodopa plasma bioavailability in PD patients."( Chronic levodopa intake increases levodopa plasma bioavailability in patients with Parkinson's disease.
Muhlack, S; Müller, T; Przuntek, H; Twiehaus, S; Welnic, J; Woitalla, D, 2004
)
0.32
"Ropinirole, a recent introduction in the clinical treatment of Parkinson's disease, suffers with the problems of low oral bioavailability and frequent dosing."( Oil based nanocarrier system for transdermal delivery of ropinirole: a mechanistic, pharmacokinetic and biochemical investigation.
Ahmad, FJ; Azeem, A; Iqbal, Z; Khar, RK; Negi, LM; Talegaonkar, S, 2012
)
0.38
" The stronger in vivo effect of (+)-catechin on L-DOPA methylation compared to the other dietary compounds is due to its better bioavailability in vivo."( Beneficial effects of natural phenolics on levodopa methylation and oxidative neurodegeneration.
Fukui, M; Kang, KS; Wen, Y; Yamabe, N; Zhu, BT, 2013
)
0.39
" Bioavailability of metal ions in ocean habitats varies significantly owing to natural and anthropogenic inputs on both short and geological spatio-temporal scales leading to large variations in byssal thread metal composition; however, it is not clear how or if this affects thread performance."( Mechanical homeostasis of a DOPA-enriched biological coating from mussels in response to metal variation.
Bertinetti, L; Harrington, MJ; Masic, A; Schmitt, CN; Strauch, P; Winter, A, 2015
)
0.42
" The bioavailability and pharmacological properties of the ligands were determined using OSIRIS server."( Bioavailability and Neuroprotectivity of 3-(3, 4-dimethoxy phenyl)-1-4 (methoxy phenyl) prop-2-en-1-one against Schizophrenia: an
Chintha, V; Wudayagiri, R,
)
0.13
" However, developing systems with satisfactory adhesion under wet conditions and adequate drug bioavailability still remains a challenge."( A mussel-inspired film for adhesion to wet buccal tissue and efficient buccal drug delivery.
Chen, J; Chen, T; Duan, L; Hu, S; Ji, P; Liu, Y; Pei, X; Wan, Q; Wang, J; Zhu, Z, 2021
)
0.62
" Nevertheless, there are still limitations with bioavailability and extended redox control with regard to antioxidant drug delivery."( Extending the Bioavailability of Hydrophilic Antioxidants for Metal Ion Detoxification via Crystallization with Polysaccharide Dopamine.
Flaherty, D; Han, HS; Kim, B; Kim, Y; Kim, YJ; Kong, H; Lee, J; Miller, R; Park, CG; Torres, C, 2022
)
0.72

Dosage Studied

ExcerptRelevanceReference
" Besides theoretical considerations relating to biochemical and pathophysiological spheres, the question of the current dosage for clinical usage seems to be of the utmost importance."( [Infusion therapy with mif (melanocyte inhibiting factor) in Parkinson's disease (author's transl)].
Binder, H; Gerstenbrand, F; Kozma, C; Pusch, ST; Reisner, Th, 1975
)
0.25
"2 mg/kg) of apomorphine reduced locomotion in a dose-dependent manner, while the reduction after higher doses was less pronounced, indicating a biphasic dose-response relationship."( Catecholamine receptor agonists: effects on motor activity and rate of tyrosine hydroxylation in mouse brain.
Strömbom, U, 1976
)
0.26
" Dose-response curves for acetylcholine with and without dopamine, isoprenaline, phenylephrine and noradrenaline were obtained."( The depressor effect of dopamine on the electrical and mechanical activities of cat small intestine.
Okawa, H; Wantanabe, M, 1975
)
0.25
"Intraperitoneal injection of diazepam in moderate dosage (1--10mg/kg) to rats caused a decrease in dopa and 5-hydroxytryptophan (5-HTP) formation, measured as the accumulation of these intermediates induced by inhibition of the aromatic L-aminoacid decarboxylase by means of NSD 1015 (3-hydroxybenzylhydrazine (HCl), in limbic forebrain, striatum and the remaining hemisphere portion."( On the mode of action of diazepam on brain catecholamine metabolism.
Biswas, B; Carlsson, A, 1978
)
0.26
" This phenomenon may also contribute to explain the complex dose-response curves of apomorphine."( Agonist--antagonist interaction on dopamine receptors in brain, as reflected in the rates of tyrosine and tryptophan hydroxylation.
Carlsson, A; Kehr, W; Lindqvist, M, 1977
)
0.26
" The dose-response curves for the two last-mentioned dopamine metabolites closely follow those for MAO A and dopamine-deaminating activity, whether clorgyline or deprenil was used as MAO inhibitor."( Preferential deamination of dopamine by an A type monoamine oxidase in rat brain.
Delini-Stula, A; Maître, L; Waldmeier, PC, 1976
)
0.26
" This study was initiated following significant symptomatic worsening by the patient with supplemental ascorbic acid at a dosage of 2 g/day."( Effect of supplemental ascorbic acid in a case of torsion dystonia.
Mars, H, 1976
)
0.26
" After pretreatment with a peripheral DOPA-decarboxylase inhibitor or high dosage of cold DOPA, the distribution pattern was not modified but the levels of radioactivity were greatly enhanced."( Autoradiographic distribution study of 14C-DOPA in cat brain.
Cassano, GB; Fornaro, P; Papeschi, R; Placidi, GF, 1976
)
0.26
" Application of solutions of TOPA to cerebellar granule cells resulted in a concentration- and time-dependent neuronal death, with prolonged (24 hr) exposure producing a clear left-handed shift in the dose-response relationship from the one observed with a 60-min exposure (LD50: 4 and 29 microM, respectively)."( Characterization of 2,4,5-trihydroxyphenylalanine neurotoxicity in vitro and protective effects of ganglioside GM1: implications for Parkinson's disease.
Dal Toso, R; Facci, L; Leon, A; Moroni, F; Schiavo, N; Skaper, SD; Vantini, G, 1992
)
0.28
" The women continue on a low dosage of levodopa after 9 and 13 years of treatment, with a stable, nearly complete, symptomatic response."( Long-term treatment response and fluorodopa positron emission tomographic scanning of parkinsonism in a family with dopa-responsive dystonia.
Calne, DB; Fahn, S; Heiman, GA; Nygaard, TG; Snow, BJ; Takahashi, H, 1992
)
0.28
" dosing (65 min), and bioavailability was 40%."( Pharmacokinetics, bioavailability, metabolism, tissue distribution and urinary excretion of gamma-L-glutamyl-L-dopa in the rat.
Cummings, J; Matheson, LM; Maurice, L; Smyth, JF, 1990
)
0.28
" When levodopa alone, or levodopa plus benserazide, was given as an acute challenge to animals receiving the same treatment chronically, it was found that levodopa alone still produced increases in striatal dopamine, DOPAC and HVA in those animals dosed chronically on levodopa, but it was less effective in this respect when given with benserazide to the animals dosed with levodopa plus benserazide."( The effect of benserazide on the peripheral and central distribution and metabolism of levodopa after acute and chronic administration in the rat.
Kent, AP; Stern, GM; Webster, RA, 1990
)
0.28
" Continuous intravenous infusions of rPRL increased DOPA accumulation in the median eminence after 2 h; this effect exhibited a very steep dose-response relationship (possibly an 'all-or-none' response)."( The rapid 'tonic' and the delayed 'induction' components of the prolactin-induced activation of tuberoinfundibular dopaminergic neurons following the systemic administration of prolactin.
Demarest, KT; Moore, KE; Riegle, GD, 1986
)
0.27
"The pathogenesis of "random" fluctuations in parkinsonian mobility, which are not clearly related to the dosing schedule of levodopa, has not been determined."( Erratic gastric emptying of levodopa may cause "random" fluctuations of parkinsonian mobility.
Kurlan, R; Lichter, D; Miller, C; Nutt, JG; Rothfield, KP; Shoulson, I; Woodward, WR, 1988
)
0.27
" Dose-response studies revealed that the sensitivity and magnitude of response to ICV prolactin was markedly reduced in 12-day hypophysectomized rats."( Hypoprolactinemia induced by hypophysectomy and long-term bromocriptine treatment decreases tuberoinfundibular dopaminergic neuronal activity and the responsiveness of these neurons to prolactin.
Demarest, KT; Moore, KE; Riegle, GD, 1985
)
0.27
" Pressor dose-response relationships for noradrenaline were the same before and after L-DOPA, as well as in cats pretreated with L-DOPA for 4 days."( On the mechanism of L-dopa-induced postural hypotension in the cat.
Dhasmana, KM; Spilker, BA, 1973
)
0.25
" The dose-response relationship for hyperactivity in grouped mice following the injection of morphine sulphate has been established."( Monoamine mediation of the morphine-induced activation of mice.
Carroll, BJ; Sharp, PT, 1972
)
0.25
" The rise in brain histamine after dosage with histidine persisted for several hours, depending on the dose; with 500 mg/kg, the rise was virtually unchanged after 16 hours."( Concentration of histamine in different parts of the brain and hypophysis of rabbit: effect of treatment with histidine, certain other amino acids and histamine.
Abou, YZ; Adam, HM; Stephen, WR, 1973
)
0.25
" Improvement was sustained during this period even though the average daily dosage of L-dopa was reduced."( Treatment of Parkinsonism with Laevo-dopa.
Mawdsley, C, 1970
)
0.25
" All patients entering the trial were taking anticholinergic drugs in stable dosage and these were continued throughout."( L-dopa in Parkinsonism and the influence of previous thalamotomy.
Hughes, RC; Polgar, JG; Walton, JN; Weightman, D, 1971
)
0.25
"The blood pressure and pulse rate have been compared in a 'double blind, cross over' study involving twenty patients with idiopathic Parkinsonism receiving maximum tolerated dosage of levodopa with and without an extracerebral decarboxylase inhibitor, L-alpha-methyldopahydrazine."( Action of L- -methyldopa-hydrazine on the blood pressure of patients receiving levodopa.
Calne, DB; Petrie, A; Rao, S; Reid, JL; Vakil, SD, 1972
)
0.25
" Patients with postencephalitic Parkinsonism may respond as well as patients with Parkinson's disease to levodopa but they develop both favourable responses and side-effects at a lower dosage and require careful dosage adjustments and close surveillance."( Response of patients with postencephalitic Parkinsonism to levodopa.
Duvoisin, RC; Lobo-Antunes, J; Yahr, MD, 1972
)
0.25
" Maximal benefits with minimal side effects were achieved only by careful adjustments of the levodopa dosage as the months went by."( One to two year treatment of Parkinson's disease with levodopa.
Ansel, RD; Markham, CH; Treciokas, LJ, 1971
)
0.25
" Gas-liquid chromatographic methods were used to measure urinary acidic and alcoholic metabolites of L-DOPA, which had been administered in high oral dosage to patients with postencephalitic and idiopathic Parkinsonism."( The metabolism of orally administered L-Dopa in Parkinsonism.
Calne, DB; Karoum, F; Ruthven, CR; Sandler, M, 1969
)
0.25
" Some of the common side effects of l-dopa administration can be averted or controlled by a cautious and slow build-up to the optimal dosage level."( Treatment of Parkinson's disease with L-dopa: a current appraisal.
Kofman, O, 1971
)
0.25
" Hence we would advise that if for any reason anticholinergic drugs are to be withdrawn in patients receiving a stable dosage of levodopa this must be done slowly."( Levodopa in Parkinsonism: the effects of withdrawal of anticholinergic drugs.
Hughes, RC; Polgar, JG; Walton, JN; Weightman, D, 1971
)
0.25
"The dose-response curve for morphine-induced stimulation of striatal dopamine metabolism was shifted to the right in mice which had been withdrawn for 24 hours after chronic consumption of an ethanol-containing liquid diet."( Alterations in opiate receptor function after chronic ethanol exposure.
Hoffman, PL; Tabakoff, B; Urwyler, S, 1982
)
0.26
" Alternate-day therapy results in less cumulative dosage and may better preserve existing compensatory striatal activity."( Intermittent levodopa therapy in parkinsonism.
Koller, WC, 1983
)
0.27
" Bromocriptin dosage was gradually increased to a total dose of 30 - 40 mg daily."( [Bromocriptin in the treatment of progressive stages of Parkinson's disease (author's transl)].
Fischer, PA; Schneider, E, 1982
)
0.26
"We characterized the clinical dose-response curves for relief of parkinsonism and production of dyskinesias as a function of plasma levodopa and 3-O-methyldopa levels in six patients with advanced Parkinson's disease (PD) and fluctuating responses to oral levodopa/carbidopa."( Suppression of dyskinesias in advanced Parkinson's disease. I. Continuous intravenous levodopa shifts dose response for production of dyskinesias but not for relief of parkinsonism in patients with advanced Parkinson's disease.
Bennett, JP; Schuh, LA, 1993
)
0.29
" NPA dose-response curves for reversal of GBL-induced dopa accumulation and Ser40 phosphorylation were identical; however, only the highest dose of NPA reversed the small and variable increase in Ser19 phosphorylation."( Increased site-specific phosphorylation of tyrosine hydroxylase accompanies stimulation of enzymatic activity induced by cessation of dopamine neuronal activity.
Carr, KD; Garcia-Espana, A; Goldstein, M; Haycock, JW; Lee, KY; Lew, JY; Meller, E, 1999
)
0.3
" The neuropharmacologic effects of chronic dosing with aldicarb, AChE inhibition and dopaminergic modulation could be useful for treatment of memory deficits related to CNS disorders."( Neurochemical and behavioural effects of chronic aldicarb administration in rats.
Bacchi, S; Coppolino, MF; Palumbo, G; Pantaleoni, GC, 2001
)
0.31
" The basal firing rate was not modified by either a single dose or repeated doses of MDMA, although the latter produced a shift to the right in the dose-response curve for clonidine-induced inhibition of the firing rate (ED(50) increased by 59%) and a reduction in tyrosine hydroxylase activity (20%) in the hippocampus."( Short-term effects of 3,4-methylenedioximethamphetamine on noradrenergic activity in locus coeruleus and hippocampus of the rat.
Arrue, A; Giralt, MT; Ruiz-Ortega, JA; Ugedo, L, 2003
)
0.32
" Dopamine-deficient mice have a rightward shift in the dose-response curve to morphine on the tail-flick test (a pain sensitivity assay), suggesting either a decreased sensitivity to the analgesic effects of morphine and/or basal hyperalgesia."( Morphine reward in dopamine-deficient mice.
Hnasko, TS; Palmiter, RD; Sotak, BN, 2005
)
0.33
" By dosage analysis, we were able to detect a mutation in all patients."( High frequency of multiexonic deletion of the GCH1 gene in a Taiwanese cohort of dopa-response dystonia.
Chang, HC; Chen, RS; Huang, CC; Huang, CL; Lai, SC; Lin, JJ; Lu, CS; Wang, CY; Weng, YH; Wu-Chou, YH; Yeh, TH, 2010
)
0.36
" We retrospectively analyzed data from 17 stable HP rhesus monkeys treated long-term with chronic intermittent dosing of levodopa (LD) in an attempt to induce choreoathetoid and dystonic dyskinesias."( Dyskinesias do not develop after chronic intermittent levodopa therapy in clinically hemiparkinsonian rhesus monkeys.
Bakay, RA; Deogaonkar, M; Lieu, CA; Subramanian, T, 2011
)
0.37
" Higher plasma concentrations of levodopa during the first 2 h after dosing were followed by lower plasma concentrations during the third and fourth hours."( Plasma dopa concentrations after different preparations of levodopa in normal subjects.
Groves, MJ; Morris, JG; Parsons, RL; Trounce, JR, 1976
)
0.26
" The patients with biallelic mutations required a higher dosage (17-25 μg/kg/day), and two patients required additional treatments."( Efficacy and safety of long-term, continuous subcutaneous octreotide infusion for patients with different subtypes of KATP-channel hyperinsulinism.
Aizu, K; Fujimaru, R; Hosokawa, Y; Kawakita, R; Masue, M; Matsubara, K; Nagasaka, H; Nishibori, H; Suzuki, S; Yorifuji, T, 2013
)
0.39
" The loaded gel was administered in different doses and dosing regimens to Parkinsonian rats, and the catalepsy score and striatal DA levels were assessed."( Potential efficacy of dopamine loaded-PVP/PAA nanogel in experimental models of Parkinsonism: possible disease modifying activity.
Abd El-Rehim, HA; El-Ghazaly, MA; Rashed, ER, 2015
)
0.42
" Cytotoxicity of DOPA melanin against cervical cancer cell line showed a dose-response activity, and IC50 value was found to be 300 μg/mL."( Bioactive DOPA melanin isolated and characterised from a marine actinobacterium Streptomyces sp. MVCS6 from Versova coast.
Kamala, K; Rajaram, R; Sivaperumal, P, 2015
)
0.42
" Low levodopa dosing and antioxidants in the rotigotine patch matrix prevented cysteinyl-glycine fall."( Levodopa, placebo and rotigotine change biomarker levels for oxidative stress.
Herrman, L; Kinkel, M; Muhlack, S; Müller, T, 2017
)
0.46
" Animals received repeated dosing of either hUCB-derived plasma or vehicle at 3, 5 and 10 days after induction into MPTP lesion, then behaviourally and immunohistochemically evaluated over 56 days post-lesion."( Gutting the brain of inflammation: A key role of gut microbiome in human umbilical cord blood plasma therapy in Parkinson's disease model.
Borlongan, CV; Ehrhart, J; Lee, JY; Sanberg, PR; Tuazon, JP, 2019
)
0.51
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (1)

RoleDescription
human metaboliteAny mammalian metabolite produced during a metabolic reaction in humans (Homo sapiens).
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Drug Classes (3)

ClassDescription
hydroxyphenylalanine
tyrosine derivativeAn amino acid derivative resulting from reaction of tyrosine at the amino group or the carboxy group, any substitution of phenyl hydrogens, or from the replacement of any hydrogen of tyrosine by a heteroatom. The definition normally excludes peptides containing tyrosine residues.
non-proteinogenic alpha-amino acidAny alpha-amino acid which is not a member of the group of 23 proteinogenic amino acids.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Pathways (1)

PathwayProteinsCompounds
Catecholamine synthesis012

Protein Targets (26)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Chain A, MAJOR APURINIC/APYRIMIDINIC ENDONUCLEASEHomo sapiens (human)Potency0.22020.003245.467312,589.2998AID2517; AID2572
Chain A, TYROSYL-DNA PHOSPHODIESTERASEHomo sapiens (human)Potency0.12590.004023.8416100.0000AID485290
Chain A, Putative fructose-1,6-bisphosphate aldolaseGiardia intestinalisPotency15.81140.140911.194039.8107AID2451
Chain A, HADH2 proteinHomo sapiens (human)Potency12.58930.025120.237639.8107AID893
Chain B, HADH2 proteinHomo sapiens (human)Potency12.58930.025120.237639.8107AID893
Chain A, 2-oxoglutarate OxygenaseHomo sapiens (human)Potency12.58930.177814.390939.8107AID2147
Chain A, ATP-DEPENDENT DNA HELICASE Q1Homo sapiens (human)Potency2.51190.125919.1169125.8920AID2549
endonuclease IVEscherichia coliPotency1.99530.707912.432431.6228AID2565
15-lipoxygenase, partialHomo sapiens (human)Potency3.98110.012610.691788.5700AID887
TDP1 proteinHomo sapiens (human)Potency3.28600.000811.382244.6684AID686978; AID686979
Microtubule-associated protein tauHomo sapiens (human)Potency18.16950.180013.557439.8107AID1460; AID1468
aldehyde dehydrogenase 1 family, member A1Homo sapiens (human)Potency17.78280.011212.4002100.0000AID1030
cytochrome P450 family 3 subfamily A polypeptide 4Homo sapiens (human)Potency3.01120.01237.983543.2770AID1645841
Bloom syndrome protein isoform 1Homo sapiens (human)Potency8.91250.540617.639296.1227AID2528
polyunsaturated fatty acid lipoxygenase ALOX12Homo sapiens (human)Potency39.81071.000012.232631.6228AID1452
15-hydroxyprostaglandin dehydrogenase [NAD(+)] isoform 1Homo sapiens (human)Potency14.12540.001815.663839.8107AID894
runt-related transcription factor 1 isoform AML1bHomo sapiens (human)Potency10.06570.02007.985839.8107AID504370; AID504374; AID504375
core-binding factor subunit beta isoform 2Homo sapiens (human)Potency10.06570.02007.985839.8107AID504370; AID504374; AID504375
mitogen-activated protein kinase 1Homo sapiens (human)Potency25.11890.039816.784239.8107AID1454
DNA polymerase kappa isoform 1Homo sapiens (human)Potency0.15850.031622.3146100.0000AID588579
Glutamate receptor 1Rattus norvegicus (Norway rat)Potency0.15850.01418.602439.8107AID2572
Glutamate receptor 2Rattus norvegicus (Norway rat)Potency0.15850.001551.739315,848.9004AID2572
Glutamate receptor 3Rattus norvegicus (Norway rat)Potency0.15850.01418.602439.8107AID2572
Glutamate receptor 4Rattus norvegicus (Norway rat)Potency0.15850.01418.602439.8107AID2572
Caspase-7Homo sapiens (human)Potency15.84893.981118.585631.6228AID889
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Epidermal growth factor receptorHomo sapiens (human)IC50 (µMol)900.00000.00000.536910.0000AID1795632
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (106)

Processvia Protein(s)Taxonomy
cell surface receptor signaling pathwayEpidermal growth factor receptorHomo sapiens (human)
epidermal growth factor receptor signaling pathwayEpidermal growth factor receptorHomo sapiens (human)
positive regulation of cell population proliferationEpidermal growth factor receptorHomo sapiens (human)
MAPK cascadeEpidermal growth factor receptorHomo sapiens (human)
ossificationEpidermal growth factor receptorHomo sapiens (human)
embryonic placenta developmentEpidermal growth factor receptorHomo sapiens (human)
positive regulation of protein phosphorylationEpidermal growth factor receptorHomo sapiens (human)
hair follicle developmentEpidermal growth factor receptorHomo sapiens (human)
translationEpidermal growth factor receptorHomo sapiens (human)
signal transductionEpidermal growth factor receptorHomo sapiens (human)
epidermal growth factor receptor signaling pathwayEpidermal growth factor receptorHomo sapiens (human)
activation of phospholipase C activityEpidermal growth factor receptorHomo sapiens (human)
salivary gland morphogenesisEpidermal growth factor receptorHomo sapiens (human)
midgut developmentEpidermal growth factor receptorHomo sapiens (human)
learning or memoryEpidermal growth factor receptorHomo sapiens (human)
circadian rhythmEpidermal growth factor receptorHomo sapiens (human)
positive regulation of cell population proliferationEpidermal growth factor receptorHomo sapiens (human)
diterpenoid metabolic processEpidermal growth factor receptorHomo sapiens (human)
peptidyl-tyrosine phosphorylationEpidermal growth factor receptorHomo sapiens (human)
cerebral cortex cell migrationEpidermal growth factor receptorHomo sapiens (human)
positive regulation of cell growthEpidermal growth factor receptorHomo sapiens (human)
lung developmentEpidermal growth factor receptorHomo sapiens (human)
positive regulation of cell migrationEpidermal growth factor receptorHomo sapiens (human)
positive regulation of superoxide anion generationEpidermal growth factor receptorHomo sapiens (human)
positive regulation of peptidyl-serine phosphorylationEpidermal growth factor receptorHomo sapiens (human)
response to cobalaminEpidermal growth factor receptorHomo sapiens (human)
response to hydroxyisoflavoneEpidermal growth factor receptorHomo sapiens (human)
cellular response to reactive oxygen speciesEpidermal growth factor receptorHomo sapiens (human)
peptidyl-tyrosine autophosphorylationEpidermal growth factor receptorHomo sapiens (human)
ERBB2-EGFR signaling pathwayEpidermal growth factor receptorHomo sapiens (human)
negative regulation of epidermal growth factor receptor signaling pathwayEpidermal growth factor receptorHomo sapiens (human)
negative regulation of protein catabolic processEpidermal growth factor receptorHomo sapiens (human)
vasodilationEpidermal growth factor receptorHomo sapiens (human)
positive regulation of phosphorylationEpidermal growth factor receptorHomo sapiens (human)
ovulation cycleEpidermal growth factor receptorHomo sapiens (human)
hydrogen peroxide metabolic processEpidermal growth factor receptorHomo sapiens (human)
negative regulation of apoptotic processEpidermal growth factor receptorHomo sapiens (human)
positive regulation of MAP kinase activityEpidermal growth factor receptorHomo sapiens (human)
tongue developmentEpidermal growth factor receptorHomo sapiens (human)
positive regulation of cyclin-dependent protein serine/threonine kinase activityEpidermal growth factor receptorHomo sapiens (human)
positive regulation of DNA repairEpidermal growth factor receptorHomo sapiens (human)
positive regulation of DNA replicationEpidermal growth factor receptorHomo sapiens (human)
positive regulation of bone resorptionEpidermal growth factor receptorHomo sapiens (human)
positive regulation of DNA-templated transcriptionEpidermal growth factor receptorHomo sapiens (human)
positive regulation of vasoconstrictionEpidermal growth factor receptorHomo sapiens (human)
negative regulation of mitotic cell cycleEpidermal growth factor receptorHomo sapiens (human)
positive regulation of transcription by RNA polymerase IIEpidermal growth factor receptorHomo sapiens (human)
regulation of JNK cascadeEpidermal growth factor receptorHomo sapiens (human)
symbiont entry into host cellEpidermal growth factor receptorHomo sapiens (human)
protein autophosphorylationEpidermal growth factor receptorHomo sapiens (human)
astrocyte activationEpidermal growth factor receptorHomo sapiens (human)
positive regulation of fibroblast proliferationEpidermal growth factor receptorHomo sapiens (human)
digestive tract morphogenesisEpidermal growth factor receptorHomo sapiens (human)
positive regulation of smooth muscle cell proliferationEpidermal growth factor receptorHomo sapiens (human)
neuron projection morphogenesisEpidermal growth factor receptorHomo sapiens (human)
epithelial cell proliferationEpidermal growth factor receptorHomo sapiens (human)
positive regulation of epithelial cell proliferationEpidermal growth factor receptorHomo sapiens (human)
regulation of peptidyl-tyrosine phosphorylationEpidermal growth factor receptorHomo sapiens (human)
protein insertion into membraneEpidermal growth factor receptorHomo sapiens (human)
response to calcium ionEpidermal growth factor receptorHomo sapiens (human)
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transductionEpidermal growth factor receptorHomo sapiens (human)
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transductionEpidermal growth factor receptorHomo sapiens (human)
positive regulation of synaptic transmission, glutamatergicEpidermal growth factor receptorHomo sapiens (human)
positive regulation of glial cell proliferationEpidermal growth factor receptorHomo sapiens (human)
morphogenesis of an epithelial foldEpidermal growth factor receptorHomo sapiens (human)
eyelid development in camera-type eyeEpidermal growth factor receptorHomo sapiens (human)
response to UV-AEpidermal growth factor receptorHomo sapiens (human)
positive regulation of mucus secretionEpidermal growth factor receptorHomo sapiens (human)
regulation of ERK1 and ERK2 cascadeEpidermal growth factor receptorHomo sapiens (human)
positive regulation of ERK1 and ERK2 cascadeEpidermal growth factor receptorHomo sapiens (human)
cellular response to amino acid stimulusEpidermal growth factor receptorHomo sapiens (human)
cellular response to mechanical stimulusEpidermal growth factor receptorHomo sapiens (human)
cellular response to cadmium ionEpidermal growth factor receptorHomo sapiens (human)
cellular response to epidermal growth factor stimulusEpidermal growth factor receptorHomo sapiens (human)
cellular response to estradiol stimulusEpidermal growth factor receptorHomo sapiens (human)
cellular response to xenobiotic stimulusEpidermal growth factor receptorHomo sapiens (human)
cellular response to dexamethasone stimulusEpidermal growth factor receptorHomo sapiens (human)
positive regulation of canonical Wnt signaling pathwayEpidermal growth factor receptorHomo sapiens (human)
liver regenerationEpidermal growth factor receptorHomo sapiens (human)
cell-cell adhesionEpidermal growth factor receptorHomo sapiens (human)
positive regulation of protein kinase C activityEpidermal growth factor receptorHomo sapiens (human)
positive regulation of G1/S transition of mitotic cell cycleEpidermal growth factor receptorHomo sapiens (human)
positive regulation of non-canonical NF-kappaB signal transductionEpidermal growth factor receptorHomo sapiens (human)
positive regulation of prolactin secretionEpidermal growth factor receptorHomo sapiens (human)
positive regulation of miRNA transcriptionEpidermal growth factor receptorHomo sapiens (human)
positive regulation of protein localization to plasma membraneEpidermal growth factor receptorHomo sapiens (human)
negative regulation of cardiocyte differentiationEpidermal growth factor receptorHomo sapiens (human)
neurogenesisEpidermal growth factor receptorHomo sapiens (human)
multicellular organism developmentEpidermal growth factor receptorHomo sapiens (human)
positive regulation of kinase activityEpidermal growth factor receptorHomo sapiens (human)
cell surface receptor protein tyrosine kinase signaling pathwayEpidermal growth factor receptorHomo sapiens (human)
proteolysisCaspase-7Homo sapiens (human)
apoptotic processCaspase-7Homo sapiens (human)
heart developmentCaspase-7Homo sapiens (human)
response to UVCaspase-7Homo sapiens (human)
protein processingCaspase-7Homo sapiens (human)
protein catabolic processCaspase-7Homo sapiens (human)
defense response to bacteriumCaspase-7Homo sapiens (human)
fibroblast apoptotic processCaspase-7Homo sapiens (human)
striated muscle cell differentiationCaspase-7Homo sapiens (human)
neuron apoptotic processCaspase-7Homo sapiens (human)
protein maturationCaspase-7Homo sapiens (human)
lymphocyte apoptotic processCaspase-7Homo sapiens (human)
cellular response to lipopolysaccharideCaspase-7Homo sapiens (human)
cellular response to staurosporineCaspase-7Homo sapiens (human)
execution phase of apoptosisCaspase-7Homo sapiens (human)
positive regulation of plasma membrane repairCaspase-7Homo sapiens (human)
positive regulation of neuron apoptotic processCaspase-7Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (31)

Processvia Protein(s)Taxonomy
epidermal growth factor receptor activityEpidermal growth factor receptorHomo sapiens (human)
virus receptor activityEpidermal growth factor receptorHomo sapiens (human)
chromatin bindingEpidermal growth factor receptorHomo sapiens (human)
double-stranded DNA bindingEpidermal growth factor receptorHomo sapiens (human)
MAP kinase kinase kinase activityEpidermal growth factor receptorHomo sapiens (human)
protein tyrosine kinase activityEpidermal growth factor receptorHomo sapiens (human)
transmembrane receptor protein tyrosine kinase activityEpidermal growth factor receptorHomo sapiens (human)
transmembrane signaling receptor activityEpidermal growth factor receptorHomo sapiens (human)
epidermal growth factor receptor activityEpidermal growth factor receptorHomo sapiens (human)
integrin bindingEpidermal growth factor receptorHomo sapiens (human)
protein bindingEpidermal growth factor receptorHomo sapiens (human)
calmodulin bindingEpidermal growth factor receptorHomo sapiens (human)
ATP bindingEpidermal growth factor receptorHomo sapiens (human)
enzyme bindingEpidermal growth factor receptorHomo sapiens (human)
kinase bindingEpidermal growth factor receptorHomo sapiens (human)
protein kinase bindingEpidermal growth factor receptorHomo sapiens (human)
protein phosphatase bindingEpidermal growth factor receptorHomo sapiens (human)
protein tyrosine kinase activator activityEpidermal growth factor receptorHomo sapiens (human)
transmembrane receptor protein tyrosine kinase activator activityEpidermal growth factor receptorHomo sapiens (human)
ubiquitin protein ligase bindingEpidermal growth factor receptorHomo sapiens (human)
identical protein bindingEpidermal growth factor receptorHomo sapiens (human)
cadherin bindingEpidermal growth factor receptorHomo sapiens (human)
actin filament bindingEpidermal growth factor receptorHomo sapiens (human)
ATPase bindingEpidermal growth factor receptorHomo sapiens (human)
epidermal growth factor bindingEpidermal growth factor receptorHomo sapiens (human)
RNA bindingCaspase-7Homo sapiens (human)
aspartic-type endopeptidase activityCaspase-7Homo sapiens (human)
cysteine-type endopeptidase activityCaspase-7Homo sapiens (human)
protein bindingCaspase-7Homo sapiens (human)
peptidase activityCaspase-7Homo sapiens (human)
cysteine-type peptidase activityCaspase-7Homo sapiens (human)
cysteine-type endopeptidase activity involved in apoptotic processCaspase-7Homo sapiens (human)
cysteine-type endopeptidase activity involved in execution phase of apoptosisCaspase-7Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (28)

Processvia Protein(s)Taxonomy
endosomeEpidermal growth factor receptorHomo sapiens (human)
plasma membraneEpidermal growth factor receptorHomo sapiens (human)
ruffle membraneEpidermal growth factor receptorHomo sapiens (human)
Golgi membraneEpidermal growth factor receptorHomo sapiens (human)
extracellular spaceEpidermal growth factor receptorHomo sapiens (human)
nucleusEpidermal growth factor receptorHomo sapiens (human)
cytoplasmEpidermal growth factor receptorHomo sapiens (human)
endosomeEpidermal growth factor receptorHomo sapiens (human)
endoplasmic reticulum membraneEpidermal growth factor receptorHomo sapiens (human)
plasma membraneEpidermal growth factor receptorHomo sapiens (human)
focal adhesionEpidermal growth factor receptorHomo sapiens (human)
cell surfaceEpidermal growth factor receptorHomo sapiens (human)
endosome membraneEpidermal growth factor receptorHomo sapiens (human)
membraneEpidermal growth factor receptorHomo sapiens (human)
basolateral plasma membraneEpidermal growth factor receptorHomo sapiens (human)
apical plasma membraneEpidermal growth factor receptorHomo sapiens (human)
cell junctionEpidermal growth factor receptorHomo sapiens (human)
clathrin-coated endocytic vesicle membraneEpidermal growth factor receptorHomo sapiens (human)
early endosome membraneEpidermal growth factor receptorHomo sapiens (human)
nuclear membraneEpidermal growth factor receptorHomo sapiens (human)
membrane raftEpidermal growth factor receptorHomo sapiens (human)
perinuclear region of cytoplasmEpidermal growth factor receptorHomo sapiens (human)
multivesicular body, internal vesicle lumenEpidermal growth factor receptorHomo sapiens (human)
intracellular vesicleEpidermal growth factor receptorHomo sapiens (human)
protein-containing complexEpidermal growth factor receptorHomo sapiens (human)
receptor complexEpidermal growth factor receptorHomo sapiens (human)
Shc-EGFR complexEpidermal growth factor receptorHomo sapiens (human)
basal plasma membraneEpidermal growth factor receptorHomo sapiens (human)
plasma membraneGlutamate receptor 1Rattus norvegicus (Norway rat)
plasma membraneGlutamate receptor 2Rattus norvegicus (Norway rat)
extracellular spaceCaspase-7Homo sapiens (human)
nucleusCaspase-7Homo sapiens (human)
cytoplasmCaspase-7Homo sapiens (human)
cytosolCaspase-7Homo sapiens (human)
nucleusCaspase-7Homo sapiens (human)
nucleoplasmCaspase-7Homo sapiens (human)
cytosolCaspase-7Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (16)

Assay IDTitleYearJournalArticle
AID307315Inhibition of p56lck SH2 domain by ELISA2007Bioorganic & medicinal chemistry, Jun-01, Volume: 15, Issue:11
The structure-activity relationship of the series of non-peptide small antagonists for p56lck SH2 domain.
AID1194159Antioxidant activity assessed as rate constant for methyl radical scavenging activity using DMPO spin trap by ESR spin-trapping method2015Bioorganic & medicinal chemistry letters, Apr-15, Volume: 25, Issue:8
Evaluation of scavenging rate constants of DOPA and tyrosine enantiomers against multiple reactive oxygen species and methyl radical as measured with ESR trapping method.
AID1194153Antioxidant activity assessed as rate constant for superoxide anion radical scavenging activity using CYPMPO spin trap by ESR spin-trapping method2015Bioorganic & medicinal chemistry letters, Apr-15, Volume: 25, Issue:8
Evaluation of scavenging rate constants of DOPA and tyrosine enantiomers against multiple reactive oxygen species and methyl radical as measured with ESR trapping method.
AID1194152Antioxidant activity assessed as superoxide anion radical scavenging activity by measuring relative rate constant (kAOx/kST ratio) using CYPMPO spin trap by ESR spin-trapping method2015Bioorganic & medicinal chemistry letters, Apr-15, Volume: 25, Issue:8
Evaluation of scavenging rate constants of DOPA and tyrosine enantiomers against multiple reactive oxygen species and methyl radical as measured with ESR trapping method.
AID1194161Antioxidant activity assessed as rate constant for singlet oxygen radical scavenging activity using 4-HO-TEMP spin trap by ESR spin-trapping method2015Bioorganic & medicinal chemistry letters, Apr-15, Volume: 25, Issue:8
Evaluation of scavenging rate constants of DOPA and tyrosine enantiomers against multiple reactive oxygen species and methyl radical as measured with ESR trapping method.
AID1194154Antioxidant activity assessed as alkoxyl radical scavenging activity by measuring relative rate constant (kAOx/kST ratio) using DMPO spin trap by ESR spin-trapping method2015Bioorganic & medicinal chemistry letters, Apr-15, Volume: 25, Issue:8
Evaluation of scavenging rate constants of DOPA and tyrosine enantiomers against multiple reactive oxygen species and methyl radical as measured with ESR trapping method.
AID781326pKa (acid-base dissociation constant) as determined by Avdeef ref: DOI: 10.1002/047145026X2014Pharmaceutical research, Apr, Volume: 31, Issue:4
Comparison of the accuracy of experimental and predicted pKa values of basic and acidic compounds.
AID1194160Antioxidant activity assessed as singlet oxygen radical scavenging activity by measuring relative rate constant (kAOx/kST ratio) using 4-HO-TEMP spin trap by ESR spin-trapping method2015Bioorganic & medicinal chemistry letters, Apr-15, Volume: 25, Issue:8
Evaluation of scavenging rate constants of DOPA and tyrosine enantiomers against multiple reactive oxygen species and methyl radical as measured with ESR trapping method.
AID1194156Antioxidant activity assessed as peroxyl radical scavenging activity by measuring relative rate constant (kAOx/kST ratio) using CYPMPO spin trap by ESR spin-trapping method2015Bioorganic & medicinal chemistry letters, Apr-15, Volume: 25, Issue:8
Evaluation of scavenging rate constants of DOPA and tyrosine enantiomers against multiple reactive oxygen species and methyl radical as measured with ESR trapping method.
AID1194158Antioxidant activity assessed as methyl radical scavenging activity by measuring relative rate constant (kAOx/kST ratio) using DMPO spin trap by ESR spin-trapping method2015Bioorganic & medicinal chemistry letters, Apr-15, Volume: 25, Issue:8
Evaluation of scavenging rate constants of DOPA and tyrosine enantiomers against multiple reactive oxygen species and methyl radical as measured with ESR trapping method.
AID1194150Antioxidant activity assessed as hydroxyl radical scavenging activity by measuring relative rate constant (kAOx/kST ratio) using DMPO spin trap by ESR spin-trapping method2015Bioorganic & medicinal chemistry letters, Apr-15, Volume: 25, Issue:8
Evaluation of scavenging rate constants of DOPA and tyrosine enantiomers against multiple reactive oxygen species and methyl radical as measured with ESR trapping method.
AID1194157Antioxidant activity assessed as rate constant for peroxyl radical scavenging activity using CYPMPO spin trap by ESR spin-trapping method2015Bioorganic & medicinal chemistry letters, Apr-15, Volume: 25, Issue:8
Evaluation of scavenging rate constants of DOPA and tyrosine enantiomers against multiple reactive oxygen species and methyl radical as measured with ESR trapping method.
AID1194155Antioxidant activity assessed as rate constant for alkoxyl radical scavenging activity using DMPO spin trap by ESR spin-trapping method2015Bioorganic & medicinal chemistry letters, Apr-15, Volume: 25, Issue:8
Evaluation of scavenging rate constants of DOPA and tyrosine enantiomers against multiple reactive oxygen species and methyl radical as measured with ESR trapping method.
AID1194151Antioxidant activity assessed as rate constant for hydroxyl radical scavenging activity using DMPO spin trap by ESR spin-trapping method2015Bioorganic & medicinal chemistry letters, Apr-15, Volume: 25, Issue:8
Evaluation of scavenging rate constants of DOPA and tyrosine enantiomers against multiple reactive oxygen species and methyl radical as measured with ESR trapping method.
AID307316Inhibition of Jurkat cell activation assessed as blocking of T-cell antigen receptor-induced IL-2 expression at 10 uM by luciferase assay2007Bioorganic & medicinal chemistry, Jun-01, Volume: 15, Issue:11
The structure-activity relationship of the series of non-peptide small antagonists for p56lck SH2 domain.
AID1795632EGFR assay from Article 10.1021/jm00130a020: \\Tyrphostins I: synthesis and biological activity of protein tyrosine kinase inhibitors.\\1989Journal of medicinal chemistry, Oct, Volume: 32, Issue:10
Tyrphostins I: synthesis and biological activity of protein tyrosine kinase inhibitors.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (8,268)

TimeframeStudies, This Drug (%)All Drugs %
pre-19905516 (66.72)18.7374
1990's1062 (12.84)18.2507
2000's764 (9.24)29.6817
2010's719 (8.70)24.3611
2020's207 (2.50)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 40.18

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be strong demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index40.18 (24.57)
Research Supply Index9.12 (2.92)
Research Growth Index4.35 (4.65)
Search Engine Demand Index67.63 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (40.18)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials322 (3.65%)5.53%
Reviews541 (6.13%)6.00%
Case Studies246 (2.79%)4.05%
Observational5 (0.06%)0.25%
Other7,709 (87.37%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (18)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
A Pilot Study Evaluating the Utility of 18F-DOPA PET for Radiotherapy Treatment Planning of Malignant Glioma Patients [NCT02104310]25 participants (Actual)Observational2014-04-30Active, not recruiting
Pilot Imaging Study for CNS Metabolism [NCT06150547]10 participants (Anticipated)Observational2023-11-14Enrolling by invitation
18F-DOPA II - PET Imaging Optimization [NCT04706910]Phase 3800 participants (Anticipated)Interventional2021-01-20Recruiting
Randomized Metabolic Response Monitoring Trial in Patients With Suspected Recurrence of Glioblastoma FDOPA PET-CT [NCT02176720]Phase 131 participants (Actual)Interventional2014-05-31Terminated(stopped due to PI left HMRI)
Localization of Focal Forms of Hyperinsulinism of Infancy With 18F-labeled L-fluoro-DOPA PET Scan [NCT00674440]Phase 2106 participants (Actual)Interventional2004-12-31Completed
Evaluation of 68Ga-DOTATATE PET/CT, Octreotide and F-DOPA PET Imaging in Patients With Ectopic Cushing Syndrome [NCT02019706]Phase 280 participants (Anticipated)Interventional2014-02-12Recruiting
Dopaminergic Effects on Cortical Function in Tourette's (Levodopa Protocol) [NCT00634556]Phase 149 participants (Actual)Interventional2006-02-28Completed
Phase II Study of the Use of [18F]-DOPA in Hyperinsulinemic Hypoglycemia [NCT02533219]0 participants Expanded AccessNo longer available
The Effects of Mood Symptoms Treatment on Quality of Life and Motor Function in de Novo Parkinson's Disease Patients [NCT04590612]30 participants (Anticipated)Interventional2021-01-31Not yet recruiting
FDG and FDOPA PET Demonstration of Functional Brain Abnormalities [NCT04315584]Early Phase 15 participants (Anticipated)Interventional2020-03-15Recruiting
A Phase IIa, Randomized, Double Blind, Placebo Controlled, Single Ascending Dose, Safety and Pharmacokinetic/Pharmacodynamic Study of INP103 (POD L-dopa) Administered in the Presence of DCI to L-dopa Responsive Parkinson's Disease Patients [NCT03541356]Phase 232 participants (Actual)Interventional2018-05-08Completed
Assessment of Carbidopa/l-Dopa and Carbidopa/l Dopa/Entacapone on Synaptic Dopamine in Parkinson's Patients: An Open-Label Feasibility/Pilot Study With [123I]-IBZM SPECT (DOPA-SYN) [NCT00200447]Phase 23 participants (Actual)Interventional2004-03-31Completed
Evaluation of the Role of the Noradrenergic System in Pain Perception in Parkinson's Disease [NCT01504178]Phase 328 participants (Actual)Interventional2011-05-31Completed
Use of18F-DOPA PET/MRI for the Detection and Localization of Focal Forms of Hyperinsulinism [NCT05088798]Phase 2100 participants (Anticipated)Interventional2020-09-10Recruiting
The Use of Fluorodopa F 18 Positron Emission Tomography Combined With Computed Tomography in Congenital Hyperinsulinism and Insulinoma [NCT02021604]Phase 1250 participants (Anticipated)Interventional2013-10-09Recruiting
FDOPA-PET/MRI for the Pre-operative Evaluation of Gliomas [NCT02371031]Phase 111 participants (Actual)Interventional2015-03-31Terminated(stopped due to Funding source for study ended.)
A Fixed Dose, Dose-response Study of Ropinirole Prolonged Release (PR) as Adjunctive Treatment to L-dopa in Patients With Advanced Parkinson's Disease [NCT01494532]Phase 4352 participants (Actual)Interventional2012-04-02Completed
18F-FDOPA PET/CT or PET/MRI in Patients With Gliomas [NCT02175745]2 participants (Actual)Interventional2014-12-31Terminated(stopped due to Re-evaluate indication with the referring physicians)
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT00674440 (2) [back to overview]Safety of F-DOPA PET
NCT00674440 (2) [back to overview]The Accuracy of FDOPA PET to Identify Focal Forms of Hyperinsulinism
NCT01494532 (24) [back to overview]"Change From Baseline in UPDRS Activities of Daily Living (ADL) Score With Participants in an on State, at Week 4 of the Maintenance Period"
NCT01494532 (24) [back to overview]"Change From Baseline in UPDRS ADL Score With Participants in an Off State, at Week 4 of the Maintenance Period"
NCT01494532 (24) [back to overview]"Percent Change From Baseline in Awake Time Spent Off at Week 4 of the Maintenance Period"
NCT01494532 (24) [back to overview]"Change From Baseline in Unified Parkinson Disease Rating Scale (UPDRS) Motor Score With Participants in an on State, at Week 4 of the Maintenance Period"
NCT01494532 (24) [back to overview]"Percent Change From Baseline in Awake Time Spent on at Week 4 of the Maintenance Period"
NCT01494532 (24) [back to overview]"Percent Change From Baseline in Awake Time Spent on Without TD at Week 4 of the Maintenance Period"
NCT01494532 (24) [back to overview]=1 Hour Reduction in Baseline Off Time at Week 4 of the Maintenance Period"-NCT01494532">"Percentage of Participants With a >=1 Hour Reduction in Baseline Off Time at Week 4 of the Maintenance Period"
NCT01494532 (24) [back to overview]=2 Hours Reduction in Baseline Off Time at Week 4 of the Maintenance Period"-NCT01494532">"Percentage of Participants With a >=2 Hours Reduction in Baseline Off Time at Week 4 of the Maintenance Period"
NCT01494532 (24) [back to overview]"Responder Rate Defined as the Percentage of Participants With a 20% Reduction in Baseline (BL) Off Time at Week-4 of Maintenance Period"
NCT01494532 (24) [back to overview]Change From Baseline for Total Sleep Time During the Night Time Hours of Sleep at Week 4 of the Maintenance Period
NCT01494532 (24) [back to overview]Change From Baseline in Total Sleep Time During the Night Time Hours of Sleep as a Percentage of a 24-hour Day, at Week 4 of the Maintenance Period
NCT01494532 (24) [back to overview]Percent Change From Baseline in Total Sleep Time During the Night Time Hours of Sleep, at Week 4 of the Maintenance Period
NCT01494532 (24) [back to overview]Percentage of Participants Withdrawn From the Study Due to Lack of Efficacy
NCT01494532 (24) [back to overview]Responder Rate According to the Clinical Global Impression-global Improvement (CGI-I) Scale at Week 4 of the Maintenance Period
NCT01494532 (24) [back to overview]"Change From Baseline in the Percent Awake Time Spent on at Week 4 of the Maintenance Period"
NCT01494532 (24) [back to overview]"Change From Baseline (BL) in Total Awake Time Spent Off at Week 4 of Maintenance Period"
NCT01494532 (24) [back to overview]"Change From Baseline in Absolute Awake Time Spent on at Week 4 of the Maintenance Period"
NCT01494532 (24) [back to overview]"Change From Baseline in Absolute Awake Time Spent on Without Troublesome Dyskinesia (TD) at Week 4 of the Maintenance Period"
NCT01494532 (24) [back to overview]"Change From Baseline in the Percent Awake Time Spent Off at Week 4 of the Maintenance Period"
NCT01494532 (24) [back to overview]Change From Baseline in UPDRS Part I at Week 4 of the Maintenance Period
NCT01494532 (24) [back to overview]"Change From Baseline in the Percent Awake Time Spent on Without TD at Week 4 of the Maintenance Period"
NCT01494532 (24) [back to overview]"Change From Baseline in the Percent of a 24- Hour Day Spent on Without TD at Week 4 of the Maintenance Period"
NCT01494532 (24) [back to overview]"Change From Baseline in the Percent of a 24-hour Day Spent Off at Week 4 of the Maintenance Period"
NCT01494532 (24) [back to overview]"Change From Baseline in the Percent of a 24-hour Day Spent on at Week 4 of the Maintenance Period"
NCT02175745 (2) [back to overview]Number of Suspicious Lesions Identified by 18F FDOPA PET
NCT02175745 (2) [back to overview]Percent Agreement of 18F FDOPA PET With Pathology
NCT03541356 (15) [back to overview]"Assessment of Time to ON as Evaluated by Subject Self-assessment"
NCT03541356 (15) [back to overview]"Subjective Time to ON as Evaluated by the Investigator"
NCT03541356 (15) [back to overview]AUC0-2h for Carbidopa
NCT03541356 (15) [back to overview]Cmax of Carbidopa
NCT03541356 (15) [back to overview]Cmax of L-dopa
NCT03541356 (15) [back to overview]Duration of Response, Where Response is Defined as an Improvement of 30% in MDS-UPDRS Part III Score From Baseline.
NCT03541356 (15) [back to overview]Mean Maximum Change From Baseline in MDS-UPDRS Part III Score
NCT03541356 (15) [back to overview]Number of Participants With Treatment Emergent Adverse Events
NCT03541356 (15) [back to overview]Time to Response (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline)
NCT03541356 (15) [back to overview]Tmax of Carbidopa
NCT03541356 (15) [back to overview]Tmax of L-dopa
NCT03541356 (15) [back to overview]Area Under the Curve (AUC) of Change From Baseline in MDS-UPDRS Part III Scores
NCT03541356 (15) [back to overview]Cumulative Number of Responders (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline)
NCT03541356 (15) [back to overview]AUC0-2hr for L-dopa
NCT03541356 (15) [back to overview]Mean Change From Baseline in MDS-UPDRS Score Over 2 Hours for C1, C2, C3 and Change From Baseline at 30, 60, 90, 120 Minutes for C4, in MDS-UPDRS Part III Score

Safety of F-DOPA PET

Number of Participants with Adverse Events (NCT00674440)
Timeframe: 72 hours maximum or prior to pancreatic surgery

InterventionParticipants (Count of Participants)
All Subjects Who Had PET0

[back to top]

The Accuracy of FDOPA PET to Identify Focal Forms of Hyperinsulinism

Comparison of PET scan results with outcome of surgery and histopathology results confirmed as focal or diffuse (NCT00674440)
Timeframe: up to 1 month post surgical intervention

InterventionParticipants (Count of Participants)
True Negatives (PET diffuse/surgery diffuse)False negatives (PET diffuse/surgery focal):False positives (PET focal/surgery diffuse):True positives (PET focal/surgery focal):
Subjects Who Had PET and Surgery406346

[back to top]

"Change From Baseline in UPDRS Activities of Daily Living (ADL) Score With Participants in an on State, at Week 4 of the Maintenance Period"

"The UPDRS Part II is the ADL score and can range from 0 to 52 as determined by the physician. The higher score indicates the worse condition. Test were performed when the par. is in the on state of PD. BL is defined as the last non-missing assessment measured on or before the first dose date. The change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values. LS means, 95% CIs and P-values were estimated from MMRM." (NCT01494532)
Timeframe: Baseline and Week 4 of the Maintenance Period (Study Week 17)

InterventionScore on scale (Least Squares Mean)
Treatment Group A: Placebo-1.32
Treatment Group B: 4 mg/Day-3.08
Treatment Group C: 8 mg/Day-3.06
Treatment Group D: 12 mg/Day-2.18
Treatment Group E: 16 mg/Day-2.63
Treatment Group F: 24 mg/Day-3.04

[back to top]

"Change From Baseline in UPDRS ADL Score With Participants in an Off State, at Week 4 of the Maintenance Period"

"The UPDRS Part II is the ADL score and can range from 0 to 52 as determined by the physician. The higher score indicates the worse condition. Test was performed when the par is in the off state of PD. The off time is defined as the state in which the participants' symptoms include lack of mobility (bradykinesia) with or without additional features such as tremor or rigidity. BL is defined as the last non-missing assessment measured on or before the first dose date. The change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values. LS means, 95% CIs and P-values were estimated from MMRM." (NCT01494532)
Timeframe: Baseline and Week 4 of the Maintenance Period (Study Week 17)

InterventionScore on scale (Least Squares Mean)
Treatment Group A: Placebo-2.94
Treatment Group B: 4 mg/Day-4.50
Treatment Group C: 8 mg/Day-4.72
Treatment Group D: 12 mg/Day-4.29
Treatment Group E: 16 mg/Day-5.76
Treatment Group F: 24 mg/Day-4.77

[back to top]

"Percent Change From Baseline in Awake Time Spent Off at Week 4 of the Maintenance Period"

"The off state is defined as the state in which the participants' symptoms include lack of mobility (bradykinesia), with or without additional features such as tremor or rigidity. Par. were asked to record awake time off, awake time on, TD during awake time on, or time asleep for all 30 minute time intervals in 24 hour diary cards for the 2 days preceding each visit of the study. The total number of awake hours spent off per 24-hour period was the average across the 2 diary cards of the sum of awake hours spent off in each 24-hour diary card. The percent change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values divided by BL values multiplied (×) the results with 100. LS means, 95% CIs and P-values were estimated from MMRM." (NCT01494532)
Timeframe: Baseline and Week 4 of the Maintenance Period (Study Week 17)

Intervention"Percentage of off time in hours" (Least Squares Mean)
Treatment Group A: Placebo-30.44
Treatment Group B: 4 mg/Day-30.47
Treatment Group C: 8 mg/Day-46.65
Treatment Group D: 12 mg/Day-37.26
Treatment Group E: 16 mg/Day-48.36
Treatment Group F: 24 mg/Day-34.37

[back to top]

"Change From Baseline in Unified Parkinson Disease Rating Scale (UPDRS) Motor Score With Participants in an on State, at Week 4 of the Maintenance Period"

"The UPDRS is a clinician based rating scale used to measure motor impairments and disability. The UPDRS assesses six features of PD impairment. These are evaluated using a combination of data collected by interview and examination of the par.. One of the six features include the Part III-motor examination where scores can range 0 to 108 with par. in an on state where the maximum score indicates the worse condition. BL is defined as the last non-missing assessment measured on or before the first dose date. The change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values. LS means, 95% CIs and P-values were estimated from MMRM." (NCT01494532)
Timeframe: Baseline and Week 4 of the Maintenance Period (Study Week 17)

InterventionScore on scale (Least Squares Mean)
Treatment Group A: Placebo-4.75
Treatment Group B: 4 mg/Day-10.38
Treatment Group C: 8 mg/Day-8.43
Treatment Group D: 12 mg/Day-8.34
Treatment Group E: 16 mg/Day-8.86
Treatment Group F: 24 mg/Day-10.06

[back to top]

"Percent Change From Baseline in Awake Time Spent on at Week 4 of the Maintenance Period"

"Par. were asked to recordawake time off, awake time on, TD during awake time on, or time asleep for all 30 minute time intervals in 24 hour diary cards for the 2 days preceding each visit of the study. The total number of awake hours spent on per 24-hour period was the average across the 2 diary cards of the sum of awake hours spent on in each 24-hour diary card. The percent change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values divided by BL values × 100. LS means, 95% CIs and P-values were estimated from MMRM." (NCT01494532)
Timeframe: Baseline and Week 4 of the Maintenance Period (Study Week 17)

Intervention"Percentage of on time in hours" (Least Squares Mean)
Treatment Group A: Placebo21.31
Treatment Group B: 4 mg/Day15.05
Treatment Group C: 8 mg/Day35.68
Treatment Group D: 12 mg/Day31.28
Treatment Group E: 16 mg/Day32.34
Treatment Group F: 24 mg/Day32.43

[back to top]

"Percent Change From Baseline in Awake Time Spent on Without TD at Week 4 of the Maintenance Period"

"Dyskinesias are involuntary twisting, turning movements caused by medication during on time in PD. TD is defined as those movements that interfere with function and cause meaningful discomfort. Par. were asked to record awake time off, awake time on, TD during awake time on, or time asleep for all 30 minute time intervals in 24 hour diary cards for the 2 days preceding each visit of the study. The total number of awake hours spent on without TD per 24-hour period was the average across the 2 diary cards of the sum of awake hours spent on without TD in each 24-hour diary card. The percent change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values divided by BL values × 100. LS means, 95% CIs and P-values were estimated from MMRM." (NCT01494532)
Timeframe: Baseline and Week 4 of the Maintenance Period (Study Week 17)

Intervention"Percentage of on time in hours" (Least Squares Mean)
Treatment Group A: Placebo24.55
Treatment Group B: 4 mg/Day15.20
Treatment Group C: 8 mg/Day35.20
Treatment Group D: 12 mg/Day32.02
Treatment Group E: 16 mg/Day34.45
Treatment Group F: 24 mg/Day29.58

[back to top]
=1 Hour Reduction in Baseline Off Time at Week 4 of the Maintenance Period"-NCT01494532">

"Percentage of Participants With a >=1 Hour Reduction in Baseline Off Time at Week 4 of the Maintenance Period"

"The off time is defined as the state in which the participants' symptoms include lack of mobility (bradykinesia) with or without additional features such as tremor or rigidity. BL is defined as the last non-missing assessment measured on or before the first dose date. The percent change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values. Percentage of participants meeting the criterion (LS mean on inverse linked scale), odds ratio with 95% CI and p-value comparing against placebo were estimated by Generalized Estimating Equations (GEE) model. Baseline 'off-time', treatment, visit and treatment*visit are included in the model." (NCT01494532)
Timeframe: Baseline and Week 4 of the Maintenance Period (Study Week 17)

Interventionpercentage of participants (Least Squares Mean)
Treatment Group A: Placebo72.1
Treatment Group B: 4 mg/Day70.1
Treatment Group C: 8 mg/Day80.6
Treatment Group D: 12 mg/Day73.5
Treatment Group E: 16 mg/Day83.2
Treatment Group F: 24 mg/Day81.4

[back to top]
=2 Hours Reduction in Baseline Off Time at Week 4 of the Maintenance Period"-NCT01494532">

"Percentage of Participants With a >=2 Hours Reduction in Baseline Off Time at Week 4 of the Maintenance Period"

"The off time is defined as the state in which the participants' symptoms include lack of mobility (bradykinesia) with or without additional features such as tremor or rigidity. BL is defined as the last non-missing assessment measured on or before the first dose date. The percent change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values. Percentage of participants meeting the criterion (LS mean on inverse linked scale), odds ratio with 95% CI and p-value comparing against placebo were estimated by Generalized Estimating Equations (GEE) model. Baseline 'off-time', treatment, visit and treatment*visit are included in the model." (NCT01494532)
Timeframe: Baseline and Week 4 of the Maintenance Period (Study Week 17)

Interventionpercentage of participants (Least Squares Mean)
Treatment Group A: Placebo53.7
Treatment Group B: 4 mg/Day45.6
Treatment Group C: 8 mg/Day68.2
Treatment Group D: 12 mg/Day53.6
Treatment Group E: 16 mg/Day63.2
Treatment Group F: 24 mg/Day51.3

[back to top]

"Responder Rate Defined as the Percentage of Participants With a 20% Reduction in Baseline (BL) Off Time at Week-4 of Maintenance Period"

"The responder rate was defined as the percentage of par with greater than or equal to (>=) 20 percent (%) reduction in their individual BL off time at Week 4 of the Maintenance Period. The off time is defined as the state in which the participants' symptoms include lack of mobility (bradykinesia) with or without additional features such as tremor or rigidity. BL is defined as the last non-missing assessment measured on or before the first dose date. Responder Rate (Least Squares [LS] means on inverse linked scale), odds ratio with 95% CI and p-value comparing against placebo were estimated by Generalized Estimating Equations (GEE) model. Baseline total awake time 'Off', treatment, visit and treatment*visit are included in the model." (NCT01494532)
Timeframe: Week 4 of the Maintenance Period (Study Week 17)

Interventionpercentage of participants (Least Squares Mean)
Treatment Group A: Placebo65.4
Treatment Group B: 4 mg/Day68.0
Treatment Group C: 8 mg/Day75.4
Treatment Group D: 12 mg/Day64.3
Treatment Group E: 16 mg/Day77.9
Treatment Group F: 24 mg/Day72.0

[back to top]

Change From Baseline for Total Sleep Time During the Night Time Hours of Sleep at Week 4 of the Maintenance Period

"Par. were asked to record awake time off, awake time on, TD during awake time on, or time asleep for all 30 minute time intervals in 24 hour diary cards for the 2 days preceding each visit of the study. The total sleep hours during the night time hours of sleep was the average across the 2 diary cards of the sum of time (hours) asleep during night time in each 24-hour diary card. BL is defined as the last non-missing assessment measured on or before the first dose date. The change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values. LS means, 95% CIs and P-values were estimated from MMRM." (NCT01494532)
Timeframe: Baseline and Week 4 of the Maintenance Period (Study Week 17)

InterventionHours (Least Squares Mean)
Treatment Group A: Placebo0.22
Treatment Group B: 4 mg/Day0.86
Treatment Group C: 8 mg/Day0.22
Treatment Group D: 12 mg/Day0.15
Treatment Group E: 16 mg/Day0.14
Treatment Group F: 24 mg/Day0.04

[back to top]

Change From Baseline in Total Sleep Time During the Night Time Hours of Sleep as a Percentage of a 24-hour Day, at Week 4 of the Maintenance Period

"Par were asked to record awake time off, awake time on, TD during awake time on, or time asleep for all 30 minute time intervals in 24 hour diary cards for the 2 days preceding each visit of the study. The total sleep hours during the night time hours of sleep was the average across the 2 diary cards of the sum of time (hours) asleep during night time in each 24-hour diary card. The percentage of a 24-hour day spent asleep during the night time hours = Total sleep hours during the night time hours of sleep divided by 24 × 100. BL is defined as the last non-missing assessment measured on or before the first dose date. The change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values. LS means, 95% CIs and P-values were estimated from MMRM." (NCT01494532)
Timeframe: Baseline and Week 4 of the Maintenance Period (Study Week 17)

InterventionPercentage of time in hours (Least Squares Mean)
Treatment Group A: Placebo0.91
Treatment Group B: 4 mg/Day3.57
Treatment Group C: 8 mg/Day0.92
Treatment Group D: 12 mg/Day0.63
Treatment Group E: 16 mg/Day0.58
Treatment Group F: 24 mg/Day0.18

[back to top]

Percent Change From Baseline in Total Sleep Time During the Night Time Hours of Sleep, at Week 4 of the Maintenance Period

"Par. were asked to record awake time off, awake time on, TD during awake time on, or time asleep for all 30 minute time intervals in 24 hour diary cards for the 2 days preceding each visit of the study. The total sleep hours during the night time hours of sleep was the average across the 2 diary cards of the sum of time (hours) asleep during night time in each 24-hour diary card. BL is defined as the last non-missing assessment measured on or before the first dose date. The percent change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values divided by BL value × 100. LS means, 95% CIs and P-values were estimated from MMRM." (NCT01494532)
Timeframe: Baseline and Week 4 of the Maintenance Period (Study Week 17)

InterventionPercentage of total sleep time in hours (Least Squares Mean)
Treatment Group A: Placebo3.99
Treatment Group B: 4 mg/Day10.79
Treatment Group C: 8 mg/Day4.94
Treatment Group D: 12 mg/Day3.41
Treatment Group E: 16 mg/Day3.60
Treatment Group F: 24 mg/Day0.91

[back to top]

Percentage of Participants Withdrawn From the Study Due to Lack of Efficacy

The percentage of participants who withdrew from the study due to lack of efficacy as defined by either the participant or the investigator is presented here. All participants with a non-missing efficacy observation at Baseline and at least one post-Baseline efficacy assessment at any time during the study were analyzed. (NCT01494532)
Timeframe: From start of study treatment until end of treatment (assessed up to 18 weeks)

InterventionPercentage of participants (Number)
Treatment Group A: Placebo0
Treatment Group B: 4 mg/Day0
Treatment Group C: 8 mg/Day0
Treatment Group D: 12 mg/Day0
Treatment Group E: 16 mg/Day3
Treatment Group F: 24 mg/Day0

[back to top]

Responder Rate According to the Clinical Global Impression-global Improvement (CGI-I) Scale at Week 4 of the Maintenance Period

"The CGI-I scale allows the investigator to rate the participant's total improvement since the beginning of treatment (Baseline). Baseline is defined as the last non-missing assessment measured on or before the first dose date. The scale is rated from 1-7 where 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. The responder rate is defined as the percentage of participants with a score of 1 or 2. The Generalized Estimating Equations (GEE) model was used to determine CGI responder rate with treatment, visit, and treatment by visit interaction included in the model. Only scheduled visits were included." (NCT01494532)
Timeframe: Week 4 of the Maintenance Period (Study Week 17)

InterventionPercentage of participants (Number)
Treatment Group A: Placebo35
Treatment Group B: 4 mg/Day28
Treatment Group C: 8 mg/Day39
Treatment Group D: 12 mg/Day42
Treatment Group E: 16 mg/Day46
Treatment Group F: 24 mg/Day56

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"Change From Baseline in the Percent Awake Time Spent on at Week 4 of the Maintenance Period"

"Par. were asked to record awake time off, awake time on, TD during awake time on, or time asleep for all 30 minute time intervals in 24 hour diary cards for the 2 days preceding each visit of the study. The total number of awake hours spent on per 24-hour period was the average across the 2 diary cards of the sum of awake hours spent on in each 24-hour diary card. The percentage of awake time spent on= Awake time spent on divided by (Awake time spent on + Awake time spent off) × 100. BL is defined as the last non-missing assessment measured on or before the first dose date. The change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values. LS means, 95% CIs and P-values were estimated from MMRM." (NCT01494532)
Timeframe: Baseline and Week 4 of the Maintenance Period (Study Week 17)

Intervention"Percentage of on time in hours" (Least Squares Mean)
Treatment Group A: Placebo12.43
Treatment Group B: 4 mg/Day11.60
Treatment Group C: 8 mg/Day18.41
Treatment Group D: 12 mg/Day15.36
Treatment Group E: 16 mg/Day17.81
Treatment Group F: 24 mg/Day15.01

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"Change From Baseline (BL) in Total Awake Time Spent Off at Week 4 of Maintenance Period"

"Off time is defined as the state in which the participants(par) symptoms include lack of mobility(bradykinesia) with or without additional features such as tremor or rigidity. Par were asked to record awake time off , awake time on, troublesome dyskinesias(TD) during awake time on, or time asleep for 30 minute intervals in 24 hr diary cards for 2 days preceding visits. Total number of awake hrs spent off per 24-hr period was the average of the 2 diary cards of the sum of awake hours spent off in each 24-hr diary card. BL is the last non-missing assessment measured on or before the first dose, change from BL was calculated by subtracting the BL values from the MP Week 4 values. Mixed Model Repeated Measures (MMRM) model used BL total awake time 'Off', treatment, visit and treatment by visit" (NCT01494532)
Timeframe: Baseline and Week 4 of the Maintenance Period (Study Week 17)

InterventionHours (Least Squares Mean)
Treatment Group A: Placebo-1.91
Treatment Group B: 4 mg/Day-2.04
Treatment Group C: 8 mg/Day-2.92
Treatment Group D: 12 mg/Day-2.34
Treatment Group E: 16 mg/Day-2.80
Treatment Group F: 24 mg/Day-2.37

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"Change From Baseline in Absolute Awake Time Spent on at Week 4 of the Maintenance Period"

"Par were asked to record awake time off, awake time on, TD during awake time on, or time asleep for all 30 minute time intervals in 24 hour diary cards for the 2 days preceding each visit of the study. The total number of awake hours spent on per 24-hour period was the average across the 2 diary cards of the sum of the awake hours spent on in each 24 hour diary card. BL is defined as the last non-missing assessment measured on or before the first dose date. The change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values. LS means, 95% CIs and P-values were estimated from MMRM." (NCT01494532)
Timeframe: Baseline and Week 4 of the Maintenance Period (Study Week 17)

InterventionHours (Least Squares Mean)
Treatment Group A: Placebo1.70
Treatment Group B: 4 mg/Day1.20
Treatment Group C: 8 mg/Day2.69
Treatment Group D: 12 mg/Day2.23
Treatment Group E: 16 mg/Day2.62
Treatment Group F: 24 mg/Day2.34

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"Change From Baseline in Absolute Awake Time Spent on Without Troublesome Dyskinesia (TD) at Week 4 of the Maintenance Period"

"Dyskinesias are involuntary twisting, turning movements caused by medication during on time in Parkinson's Disease (PD). TD is defined as those movements that interfere with function and cause meaningful discomfort. Par were asked to record awake time off, awake time on, TD during awake time on, or time asleep for all 30 minute time intervals in 24 hour diary cards for the 2 days preceding each visit. The total number of awake hours spent on without TD per 24-hour period was the average across the 2 diary cards of the sum of awake hours spent on without TD in each 24 hour diary card. The change from BL was calculated by subtracting the BL values from the MP Week 4 values. LS means, 95% CIs and P-values were estimated from Mixed Model Repeated Measures (MMRM). Par with a non-missing efficacy observation at BL and during the MP were analyzed." (NCT01494532)
Timeframe: Baseline and Week 4 of the Maintenance Period (Study Week 17)

InterventionHours (Least Squares Mean)
Treatment Group A: Placebo1.76
Treatment Group B: 4 mg/Day1.21
Treatment Group C: 8 mg/Day2.69
Treatment Group D: 12 mg/Day2.16
Treatment Group E: 16 mg/Day2.49
Treatment Group F: 24 mg/Day2.24

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"Change From Baseline in the Percent Awake Time Spent Off at Week 4 of the Maintenance Period"

"The off state is defined as the state in which the participants' symptoms include lack of mobility(bradykinesia), with or without additional features such as tremor or rigidity. Par were asked to record awake time off, awake time on, TD during awake time on, or time asleep for all 30 minute time intervals in 24 hour diary cards for the 2 days preceding each visit of the study. The total number of awake hours spent off per 24-hour period was the average across the 2 diary cards of the sum of awake hours spent off in each 24-hour diary card. The percentage of awake time spent off= Awake time spent off divided by (Awake time spent off + Awake time spent on) × 100. BL is defined as the last non-missing assessment measured on or before the first dose date. The change from BL was calculated by subtracting the BL values from the MP Week 4 values. LS means, 95% CIs and P-values were estimated from MMRM." (NCT01494532)
Timeframe: Baseline and Week 4 of the Maintenance Period (Study Week 17)

Intervention"Percentage of off time in hours" (Least Squares Mean)
Treatment Group A: Placebo-12.43
Treatment Group B: 4 mg/Day-11.60
Treatment Group C: 8 mg/Day-18.41
Treatment Group D: 12 mg/Day-15.36
Treatment Group E: 16 mg/Day-17.81
Treatment Group F: 24 mg/Day-15.01

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Change From Baseline in UPDRS Part I at Week 4 of the Maintenance Period

"The UPDRS Part I scores mentation, behavior and mood as determined by a physician and par. were tested during the on phase of PD. This component of the UPDRS is the total score for 4 items (the items 1 to 4 include intellectual impairment, thought disorder, motivation / initiative, and depression) and may have a value ranging from 0 to 16 as determined by a physician. The higher score (16) indicates the maximum score and the worse condition. All 4 items have to be present for a total score to be calculated. If one or more items are missing, the total score for the component would also be missing. BL is defined as the last non-missing assessment measured on or before the first dose date. The change from BL was calculated by subtracting the BL values from the individual post-randomization values. LS means, 95% CIs and P-values were estimated from MMRM." (NCT01494532)
Timeframe: Baseline (BL) and Week 4 of the Maintenance Period (Study Week 17)

InterventionScore on scale (Least Squares Mean)
Treatment Group A: Placebo-0.24
Treatment Group B: 4 mg/Day-0.44
Treatment Group C: 8 mg/Day-0.33
Treatment Group D: 12 mg/Day-0.24
Treatment Group E: 16 mg/Day-0.47
Treatment Group F: 24 mg/Day-0.45

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"Change From Baseline in the Percent Awake Time Spent on Without TD at Week 4 of the Maintenance Period"

"Dyskinesias are involuntary twisting, turning movements caused by medication during on time in PD. TD is defined as those movements that interfere with function and cause meaningful discomfort. Par were asked to record awake time off, awake time on, TD during awake time on, or time asleep for all 30 minute time intervals in 24 hr diary cards for the 2 days preceding each visit of the study. The total number of awake hr spent on without TD per 24-hr period was the average across the 2 diary cards of the sum of awake hr spent on without TD in each 24-hr diary card. Percentage of awake time spent onwithout TD= Awake time spent on without TD divided by(Awake time spent on + Awake time spent off) × 100. BL is defined as the last non-missing assessment measured on or before the first dose date, change from BL was calculated by subtracting BL values from MP Week 4 values. LS means, 95% CIs and P-values were estimated from MMRM." (NCT01494532)
Timeframe: Baseline and Week 4 of the Maintenance Period (Study Week 17)

Intervention"Percentage of on time in hours" (Least Squares Mean)
Treatment Group A: Placebo12.89
Treatment Group B: 4 mg/Day11.58
Treatment Group C: 8 mg/Day18.34
Treatment Group D: 12 mg/Day14.99
Treatment Group E: 16 mg/Day17.05
Treatment Group F: 24 mg/Day14.56

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"Change From Baseline in the Percent of a 24- Hour Day Spent on Without TD at Week 4 of the Maintenance Period"

"Dyskinesias are involuntary twisting, turning movements caused by medication during on time in PD. TD is defined as those movements that interfere with function and cause meaningful discomfort. Par were asked to record awake time off, awake time on, TD during awake time on, or time asleep for all 30 minute time intervals in 24 hr diary cards for the 2 days preceding each visit. The total number of day awake hr spent on without TD per 24-hr period was the average across the 2 diary cards of the sum of awake hours spent on without TD in each 24-hour diary card. The percentage of 24 hr day spent on without TD= awake time spent on without TD divided by 24 × 100. BL is defined as the last non-missing assessment measured on or before the first dose date, change from BL was calculated by subtracting the BL values from the MP Week 4 values. LS means, 95% CIs and P-values were estimated from MMRM." (NCT01494532)
Timeframe: Baseline and Week 4 of the Maintenance Period (Study Week 17)

Intervention"Percentage of on time in hours" (Least Squares Mean)
Treatment Group A: Placebo7.32
Treatment Group B: 4 mg/Day5.03
Treatment Group C: 8 mg/Day11.19
Treatment Group D: 12 mg/Day8.99
Treatment Group E: 16 mg/Day10.40
Treatment Group F: 24 mg/Day9.34

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"Change From Baseline in the Percent of a 24-hour Day Spent Off at Week 4 of the Maintenance Period"

"The off state is defined as the state in which the participants' symptoms include lack of mobility (bradykinesia), with or without additional features such as tremor or rigidity. Par were asked to record awake time off, awake time on, TD during awake time on, or time asleep for all 30 minute time intervals in 24 hour diary cards for the 2 days preceding each visit of the study. The total number of day awake hours spent off per 24-hour period was the average across the 2 diary cards of the sum of awake hours spent off in each 24-hour diary card. The percentage of 24 hour day spent off= awake time spent off divided by 24 x 100. BL is defined as the last non-missing assessment measured on or before the first dose date. The change from BL was calculated by subtracting the BL values from the MP Week 4 values. LS means, 95% CIs and P-values were estimated from MMRM." (NCT01494532)
Timeframe: Baseline and Week 4 of the Maintenance Period (Study Week 17)

Intervention"Percentage of off time in hours" (Least Squares Mean)
Treatment Group A: Placebo-7.94
Treatment Group B: 4 mg/Day-8.50
Treatment Group C: 8 mg/Day-12.17
Treatment Group D: 12 mg/Day-9.75
Treatment Group E: 16 mg/Day-11.65
Treatment Group F: 24 mg/Day-9.86

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"Change From Baseline in the Percent of a 24-hour Day Spent on at Week 4 of the Maintenance Period"

"Par. were asked to record awake time off, awake time on, TD during awake time on, or time asleep for all 30 minute time intervals in 24 hour diary cards for the 2 days preceding each visit of the study. The total number of day awake hours spent on per 24-hour period was the average across the 2 diary cards of the sum of awake hours spent on in each 24-hour diary card. The percentage of a 24-hour day spent on = Awake time spent on divided by 24 × 100. BL is defined as the last non-missing assessment measured on or before the first dose date. The change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values. LS means, 95% CIs and P-values were estimated from MMRM." (NCT01494532)
Timeframe: Baseline and Week 4 of the Maintenance Period (Study Week 17)

Intervention"Percentage of on time in hours" (Least Squares Mean)
Treatment Group A: Placebo7.08
Treatment Group B: 4 mg/Day4.99
Treatment Group C: 8 mg/Day11.20
Treatment Group D: 12 mg/Day9.28
Treatment Group E: 16 mg/Day10.94
Treatment Group F: 24 mg/Day9.76

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Number of Suspicious Lesions Identified by 18F FDOPA PET

The number of suspicious lesions will be identified by uptake of F18 FDOPA radiopharmaceutical using a positron emission tomography (PET) scan. Uptake of F-18 FDOPA is a measure of amino acid uptake and metabolism in tumors. Suspicious lesions will be visually identified by a board certified nuclear medicine physician. (NCT02175745)
Timeframe: Up to 30 minutes after injection of F18 FDOPA

Interventionsuspicious lesion(s) (Number)
Diagnostic (FDOPA-PET/CT or PET/MRI)1

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Percent Agreement of 18F FDOPA PET With Pathology

For the subset of lesions where pathology is available (mainly biopsied lesions), the accuracy of 18F FDOPA PET as percent agreement with pathology will be calculated. If the number of biopsy positive lesions is at least 10, an estimate of sensitivity will be calculate; if the number of biopsy negative lesions is at least 10 an estimate of specificity will be calculated. (NCT02175745)
Timeframe: Up to 30 minutes post-injection (at time of scan)

Interventionpercentage of agreement (sensitivity) (Number)
Diagnostic (FDOPA-PET/CT or PET/MRI)100

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"Assessment of Time to ON as Evaluated by Subject Self-assessment"

"Subjects were asked to provide self-assessments at 15, 30, 45, 60, 90, 120, and 240 minutes post-dose as to whether they considered themselves to be ON." (NCT03541356)
Timeframe: 4 hours

Interventionminutes (Median)
Placebo40.0
L-dopa 35 mg240.0
L-dopa 70 mg39.0
L-dopa 140 mg30.0
L-dopa 70 mg/Carbidopa 7 mg232.5

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"Subjective Time to ON as Evaluated by the Investigator"

"Investigators will evaluate subjects' fluctuations in motor functions at 15, 30, 45, 60, 90, 120, and 240 minutes post-dose to determine if they are ON." (NCT03541356)
Timeframe: 4 hours

Interventionminutes (Median)
Placebo45.0
L-dopa 35 mg240.0
L-dopa 70 mg30.0
L-dopa 140 mg30.0
L-dopa 70 mg/Carbidopa 7 mg240.0

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AUC0-2h for Carbidopa

Area under the concentration time curve for carbidopa (NCT03541356)
Timeframe: Plasma samples were taken at pre-dose, 5, 10, 15, 30, 45, 60, 90 and 120 minutes post-dose and AUC calculated from these from time 0 to 120 minutes.

Interventionhours*ng/mL (Mean)
L-dopa 70 mg/Carbidopa 7 mg114.80

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Cmax of Carbidopa

Maximum concentration of carbidopa (NCT03541356)
Timeframe: For L-dopa 70 mg/carbidopa 7 mg, plasma samples were taken at pre-dose, 5, 10, 15, 30, 45, 60, 90 and 120 minutes post-dose.

Interventionng/mL (Mean)
L-dopa 70 mg/Carbidopa 7 mg80.23

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Cmax of L-dopa

Maximum Observed Plasma Concentration of L-dopa from Time = 0 to Time = 2 hours post dose. For the L-dopa 35 mg, L-dopa 70 mg, L-dopa 140 mg plasma samples were taken at pre-dose, 30, 60, 90 and 120 minutes post-dose. For the L-dopa 70 mg/carbidopa 7 mg treatment arm, plasma samples were taken at pre-dose, 5, 10, 15, 30, 45, 60, 90 and 120 minutes post-dose. (NCT03541356)
Timeframe: For L-dopa 35 mg, 70 mg, 140 mg plasma samples were taken at pre-dose, 30, 60, 90 and 120 minutes post-dose. For L-dopa 70 mg/carbidopa 7 mg, plasma samples were taken at pre-dose, 5, 10, 15, 30, 45, 60, 90 and 120 minutes post-dose.

Interventionng/mL (Mean)
L-dopa 35 mg185.80
L-dopa 70 mg362.68
L-dopa 140 mg643.65
L-dopa 70 mg/Carbidopa 7 mg445.75

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Duration of Response, Where Response is Defined as an Improvement of 30% in MDS-UPDRS Part III Score From Baseline.

MDS-UPDRS is a clinimetric assessment of subjective and objective symptoms and signs of Parkinson's disease created by the Movement Disorder Society with high internal consistency. MDS-UPDRS retains the four-scale structure with a reorganization of the various subscales. The subscale used in this study is Part III, motor examination (18 items). The subscale has 0-4 ratings, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. Maximum score is 132, minimum is zero. High score means worse outcome. (NCT03541356)
Timeframe: 2 hours

Interventionminutes (Mean)
Placebo66.9
L-dopa 35 mg23.3
L-dopa 70 mg57.3
L-dopa 140 mg37.5
L-dopa 70 mg/Carbidopa 7 mg15.0

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Mean Maximum Change From Baseline in MDS-UPDRS Part III Score

MDS-UPDRS is a clinimetric assessment of subjective and objective symptoms and signs of Parkinson's disease created by the Movement Disorder Society with high internal consistency. MDS-UPDRS retains the four-scale structure with a reorganization of the various subscales. The subscale used in this study is Part III, motor examination (18 items). The subscale now has 0-4 ratings, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. The total of the subscales has a maximum value of 132 and a minimum value of zero. Lower scores indicate better motor function. A negative change from baseline indicates improved motor function. (NCT03541356)
Timeframe: From time = 0 to 2 hours post-dose

Interventionscore on a scale (Mean)
Placebo-15.5
L-dopa 35 mg-14.0
L-dopa 70 mg-20.3
L-dopa 140 mg-15.3
L-dopa 70 mg/Carbidopa 7 mg-7.5

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Number of Participants With Treatment Emergent Adverse Events

Assessment of treatment emergent adverse events after single dosing with INP103 (L-dopa or L-dopa/carbidopa) (NCT03541356)
Timeframe: 7 days

InterventionParticipants (Count of Participants)
Placebo5
L-dopa 35 mg5
L-dopa 70 mg3
L-dopa 140 mg4
L-dopa 70 mg/Carbidopa 7 mg5

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Time to Response (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline)

MDS-UPDRS is a clinimetric assessment of subjective and objective symptoms and signs of Parkinson's disease created by the Movement Disorder Society with high internal consistency. MDS-UPDRS retains the four-scale structure with a reorganization of the various subscales. The subscale used in this study is Part III, motor examination (18 items). The subscale now has 0-4 ratings, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. (NCT03541356)
Timeframe: 2 hours

Interventionminutes (Median)
Placebo45.0
L-dopa 35 mgNA
L-dopa 70 mg54.0
L-dopa 140 mg30.0
L-dopa 70 mg/Carbidopa 7 mgNA

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Tmax of Carbidopa

Time to reach the maximum concentration of carbidopa (NCT03541356)
Timeframe: For L-dopa 70 mg/carbidopa 7 mg, plasma samples were taken at pre-dose, 5, 10, 15, 30, 45, 60, 90 and 120 minutes post-dose.

Interventionminutes (Mean)
L-dopa 70 mg/Carbidopa 7 mg44.50

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Tmax of L-dopa

Time to Reach the Maximum Plasma Concentration (Cmax) of L-dopa (NCT03541356)
Timeframe: For L-dopa 35 mg, 70 mg, 140 mg plasma samples were taken at pre-dose, 30, 60, 90 and 120 minutes post-dose. For L-dopa 70 mg/carbidopa 7 mg, plasma samples were taken at pre-dose, 5, 10, 15, 30, 45, 60, 90 and 120 minutes post-dose.

Interventionminutes (Mean)
L-dopa 35 mg60.17
L-dopa 70 mg66.00
L-dopa 140 mg70.00
L-dopa 70 mg/Carbidopa 7 mg92.00

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Area Under the Curve (AUC) of Change From Baseline in MDS-UPDRS Part III Scores

MDS-UPDRS is a clinimetric assessment of subjective and objective symptoms and signs of Parkinson's disease created by the Movement Disorder Society with high internal consistency. MDS-UPDRS retains the four-scale structure with a reorganization of the various subscales. The subscale used in this study is Part III, motor examination (18 items). The subscale now has 0-4 ratings, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. (NCT03541356)
Timeframe: For L-dopa 35 mg, 70 mg, 140 mg, assessments were made at pre-dose, 15, 30, 45, 60, 90, 120 minutes post-dose. For L-dopa 70 mg/carbidopa 7 mg, assessments were made at pre-dose, 50, 60, 90, 120 minutes post-dose.

,,,,
Interventionchange in score*minutes (Mean)
15 minutes30 minutes45 minutes60 minutes90 minutes120 minutes
L-dopa 140 mg-67.50-232.83-426.83-630.58-968.08-1210.58
L-dopa 35 mg-33.50-138.58-201.92-296.50-575.17-903.67
L-dopa 70 mg7.00-50.50-210.50-424.25-896.67-1324.83
L-dopa 70 mg/Carbidopa 7 mgNA-230.08NA-295.25-362.75-465.25
Placebo-26.25-237.63-264.92-573.88-919.75-1215.75

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Cumulative Number of Responders (Defined as Improvement of 30% in MDS-UPDRS Part III Score From Baseline)

MDS-UPDRS is a clinimetric assessment of subjective and objective symptoms and signs of Parkinson's disease created by the Movement Disorder Society with high internal consistency. MDS-UPDRS retains the four-scale structure with a reorganization of the various subscales. The subscale used in this study is Part III, motor examination (18 items). The subscale now has 0-4 ratings, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. (NCT03541356)
Timeframe: From time = 0 to 2 hours post-dose

,,,,
InterventionParticipants (Count of Participants)
15 minutes30 minutes45 minutes60 minutes90 minutes120 minutes
L-dopa 140 mg255555
L-dopa 35 mg011122
L-dopa 70 mg113455
L-dopa 70 mg/Carbidopa 7 mgNA1NA233
Placebo034666

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AUC0-2hr for L-dopa

Area under the Plasma Concentration-time Curve for L-dopa from Time = 0 to Time = 2 hours post dose. For the L-dopa 35 mg, L-dopa 70 mg, L-dopa 140 mg plasma samples were taken at pre-dose, 30, 60, 90 and 120 minutes post-dose. For the L-dopa 70 mg/carbidopa 7 mg treatment arm, plasma samples were taken at pre-dose, 5, 10, 15, 30, 45, 60, 90 and 120 minutes post-dose. (NCT03541356)
Timeframe: For L-dopa 35 mg, 70 mg, 140 mg plasma samples were taken at pre-dose, 30, 60, 90 and 120 minutes post-dose. For L-dopa 70 mg/carbidopa 7 mg, plasma samples were taken at pre-dose, 5, 10, 15, 30, 45, 60, 90 and 120 min

Interventionhours*ng/mL (Mean)
L-dopa 35 mg240.71
L-dopa 70 mg463.49
L-dopa 140 mg725.29
L-dopa 70 mg/Carbidopa 7 mg552.75

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Mean Change From Baseline in MDS-UPDRS Score Over 2 Hours for C1, C2, C3 and Change From Baseline at 30, 60, 90, 120 Minutes for C4, in MDS-UPDRS Part III Score

MDS-UPDRS is a clinimetric assessment of subjective and objective symptoms and signs of Parkinson's disease created by the Movement Disorder Society with high internal consistency. MDS-UPDRS retains the four-scale structure with a reorganization of the various subscales. The subscale used in this study is Part III, motor examination (18 items). The subscale has 0-4 ratings, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. Maximum score is 132, minimum is zero. High score means worse outcome. For the L-dopa 35 mg, L-dopa 70 mg, L-dopa 140 mg treatment groups, assessment occurred at pre-dose, 15, 30, 45, 60, 90 and 120 minutes post-dose. For the L-dopa 70 mg/carbidopa 7 mg treatment arm, assessment occurred at pre-dose, 30, 60, 90 and 120 minutes post-dose. (NCT03541356)
Timeframe: For L-dopa 35 mg, 70 mg, 140 mg, assessment occurred at pre-dose, 15, 30, 45, 60, 90 and 120 minutes post-dose. For L-dopa 70 mg/carbidopa 7 mg, assessment occurred at pre-dose, 30, 60, 90 and 120 minutes post-dose.

,,,,
Interventionscore on a scale (Mean)
15 minutes30 minutes45 minutes60 minutes90 minutes120 minutes
L-dopa 140 mg-9.0-12.7-13.7-13.5-9.0-7.2
L-dopa 35 mg-4.5-6.7-4.7-6.8-10.3-11.0
L-dopa 70 mg0.8-8.5-12.8-15.7-15.5-13.8
L-dopa 70 mg/Carbidopa 7 mgNA-3.7NA-0.8-3.7-3.2
Placebo-3.5-8.5-13.5-12.5-10.8-8.8

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