Details of the Drug Metabolized by Drug-Metabolizing Enzyme (DME)

General Information of Drug (ID: DR0939)
Drug Name
Levodopa
Prodrug Info Levodopa is the prodrug of Dopamine
Synonyms
Larodopa; Levedopa; Levodopum; Levopa; Maipedopa; Pardopa; Prodopa; Syndopa; Veldopa; Bendopa; Brocadopa; Cidandopa; Deadopa; Dihydroxy-L-phenylalanine; Dopaflex; Dopaidan; Dopal-fher; Dopalina; Doparkine; Doparl; Dopasol; Dopaston; Dopastral; Doprin; Eldopal; Eldopar; Eldopatec; Eurodopa; Helfo-Dopa; Insulamina; L-dopa; L-o-Hydroxytyrosine; levodopa; (-)-Dopa; (2S)-2-amino-3-(3,4-dihydroxyphenyl)propanoic acid; 3,4-Dihydroxyphenylalanine; 3,4-dihydroxy-L-phenylalanine; 3-(3,4-Dihydroxyphenyl)-L-alanine; 3-Hydroxy-L-tyrosine; 59-92-7; Dopar
Indication Parkinsonism [ICD11: 8A00] Approved [1]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 197.19 Topological Polar Surface Area 104
Heavy Atom Count 14 Rotatable Bond Count 3
Hydrogen Bond Donor Count 4 Hydrogen Bond Acceptor Count 5
Cross-matching ID
PubChem CID
6047
PubChem SID
3648 ; 222573 ; 555833 ; 3136680 ; 7847127 ; 7886892 ; 7979689 ; 8001566 ; 8143351 ; 8150164 ; 8153771 ; 10321285 ; 11111115 ; 11112155 ; 11335627 ; 11360866 ; 11363348 ; 11365910 ; 11368472 ; 11374316 ; 11376634 ; 11461838 ; 11466045 ; 11467165 ; 11484127 ; 11485710 ; 11488312 ; 11492354 ; 11494268 ; 11532916 ; 11537951 ; 15120911 ; 15219946 ; 17405017 ; 24277914 ; 24863554 ; 26613179 ; 26679497 ; 26719283 ; 26746620 ; 26753566 ; 29225059 ; 46508120 ; 47216726 ; 47291084 ; 47440197 ; 47440198 ; 47736420 ; 47810699 ; 47959681
ChEBI ID
CHEBI:15765
CAS Number
59-92-7
TTD Drug ID
D08HVR
Formula
C9H11NO4
Canonical SMILES
C1=CC(=C(C=C1CC(C(=O)O)N)O)O
InChI
1S/C9H11NO4/c10-6(9(13)14)3-5-1-2-7(11)8(12)4-5/h1-2,4,6,11-12H,3,10H2,(H,13,14)/t6-/m0/s1
InChIKey
WTDRDQBEARUVNC-LURJTMIESA-N
The Metabolic Roadmap of This Drug
The Full List of Drug Metabolites (DM) of This Drug
DM Name DM ID PubChem ID Reaction DM Level REF
3-O-methyl-alpha-methyldopa DM000289
9307
Conjugation - Methylation 1 [9] , [10] , [11] , [12]
Dopamine DM000276
681
Oxidation - Decarboxylation 1 [4]
Levodopa Methylated metabolite DM000288 N. A. Conjugation - Methylation 1 [2]
3-MT DM000277
1669
Conjugation - O-Methylation 2 [2]
DHPA DM000279
119219
Oxidation - Oxidative Deamination 2 [2]
Dopamine 3-O-sulfate DM000286
122136
Conjugation - Sulfation 2 [2]
Dopamine 4-sulfate DM000287
123932
Conjugation - Sulfation 2 [2]
Dopamine glucuronide DM000285
3082490
Oxidation - N-Dealkylation 2 [2]
Dopamine-3-O-glucuronide DM000284 N. A. Oxidation - N-Dealkylation 2 [2]
Norepinephrine DM000282
439260
Oxidation - Hydroxylation 2 [2]
(3,4-Dihydroxyphenyl)acetic acid DM000280
547
Oxidation - Hydroxylation 3 [2]
3-methoxy-4-hydroxyacetaldehyde DM000278 N. A. Oxidation - Oxidative Deamination 3 [2]
DOPET DM000281
82755
Reduction - Reduction 3 [2]
Epinephrine DM000283
5816
Conjugation - Methylation 3 [2]
HVA DM003106
1738
Conjugation - O-Methylation 4 [2]
HVA DM003106
1738
Oxidation - Oxidation 4 [2]
⏷ Show the Full List of 16  DM(s)
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR001498 Levodopa Dopamine Oxidation - Decarboxylation DDC [4]
MR001499 Levodopa Levodopa Methylated metabolite Conjugation - Methylation Unclear [2]
MR001500 Levodopa 3-O-Methyldopa Conjugation - Methylation COMT [9], [10], [11], [12]
MR001485 Dopamine 3-Methoxytyramine Conjugation - O-Methylation COMT [2]
MR001486 Dopamine 3,4-Dihydroxyphenylacetaldehyde (DOPAL) Oxidation - Oxidative Deamination MAO [2]
MR001487 Dopamine Norepinephrine Oxidation - Hydroxylation DBH [2]
MR001488 Dopamine Dopamine-3-O-glucuronide Oxidation - N-Dealkylation Unclear [2]
MR001489 Dopamine Dopamine-4-O-glucuronide Oxidation - N-Dealkylation Unclear [2]
MR001490 Dopamine Dopamine-3-O-sulfate Conjugation - Sulfation SULT1A1 ... [2]
MR001491 Dopamine Dopamine-4-O-sulfate Conjugation - Sulfation SULT1A1 ... [2]
MR001494 3,4-Dihydroxyphenylacetaldehyde (DOPAL) 3,4-dihydroxyphenylacetic acid Oxidation - Hydroxylation Unclear [2]
MR001495 3,4-Dihydroxyphenylacetaldehyde (DOPAL) 3,4-dihydroxyphenylethanol Reduction - Reduction Unclear [2]
MR001492 3-Methoxytyramine 3-methoxy-4-hydroxyacetaldehyde Oxidation - Oxidative Deamination MAO [2]
MR001497 Norepinephrine Epinephrine E Conjugation - Methylation PNMT [2]
MR001496 3,4-dihydroxyphenylacetic acid Homovanillic acid Conjugation - O-Methylation COMT [2]
MR001493 3-methoxy-4-hydroxyacetaldehyde Homovanillic acid Oxidation - Oxidation Unclear [2]
⏷ Show the Full List of 16 MR(s)
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Catechol O-methyltransferase (COMT) DME0043 Homo sapiens
COMT_HUMAN
2.1.1.6
[2]
Cytochrome P450 2D6 (CYP2D6) DME0009 Homo sapiens
CP2D6_HUMAN
1.14.14.1
[3]
DOPA decarboxylase (DDC) DME0125 Homo sapiens
DDC_HUMAN
4.1.1.28
[4]
Dopamine beta-hydroxylase (DBH) DMEN008 Homo sapiens
DOPO_HUMAN
7.1.1.9
[2]
Phenylethanolamine N-methyltransferase (PNMT) DME0543 Homo sapiens
PNMT_HUMAN
2.1.1.28
[2]
Sulfotransferase 1A1 (SULT1A1) DME0008 Homo sapiens
ST1A1_HUMAN
2.8.2.1
[2]
Sulfotransferase 1A2 (SULT1A2) DME0062 Homo sapiens
ST1A2_HUMAN
2.8.2.1
[2]
Sulfotransferase 1A3 (SULT1A3) DME0063 Homo sapiens
ST1A3_HUMAN
2.8.2.1
[2]
Sulfotransferase 1A4 (SULT1A4) DMEN007 Homo sapiens
ST1A4_HUMAN
1.14.13.39
[2]
Thiopurine methyltransferase (TPMT) DME0014 Homo sapiens
TPMT_HUMAN
2.1.1.67
[5]
Tyrosine decarboxylase (tdc) DME1061 Enterococcus faecalis
TYRDC_ENTFA
4.1.1.25
[6] , [7]
Tyrosine decarboxylase (tdc) DME1553 Lactobacillus brevis
TYRDC_LACBR
4.1.1.25
[7]
Unclear metabolic mechanism (DME-unclear) DME1430 Helicobacter pylori Not Available Not Available [8]
⏷ Show the Full List of 13  DME(s)
References
1 Levodopa was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 DrugBank(Pharmacology-Metabolism)Levodopa
3 Multiple cytochrome P450 enzymes responsible for the oxidative metabolism of the substituted (S)-3-phenylpiperidine, (S,S)-3-[3-(methylsulfonyl)phenyl]-1-propylpiperidine hydrochloride, in human liver microsomes. Drug Metab Dispos. 2002 Dec;30(12):1372-7.
4 Complexity of dopamine metabolism. Cell Commun Signal. 2013 May 17;11(1):34.
5 Reduced 3-O-methyl-dopa levels in OCD patients and their unaffected parents is associated with the low activity M158 COMT allele. Am J Med Genet B Neuropsychiatr Genet. 2010 Mar 5;153B(2):542-548.
6 Discovery and inhibition of an interspecies gut bacterial pathway for Levodopa metabolism. Science. 2019 Jun 14;364(6445). pii: eaau6323.
7 Gut bacterial tyrosine decarboxylases restrict levels of levodopa in the treatment of Parkinson's disease. Nat Commun. 2019 Jan 18;10(1):310.
8 Drug metabolism by the host and gut microbiota: a partnership or rivalry? Drug Metab Dispos. 2015 Oct;43(10):1499-504.
9 Motor complications, levodopa metabolism and progression of Parkinson's disease Expert Opin Drug Metab Toxicol. 2011 Jul;7(7):847-55. doi: 10.1517/17425255.2011.575779.
10 Impact of the catechol-O-methyltransferase Val158Met polymorphism on the pharmacokinetics of L-dopa and its metabolite 3-O-methyldopa in combination with entacapone. J Neural Transm (Vienna). 2021 Jan;128(1):27-36. doi: 10.1007/s00702-020-02267-y.
11 Mass spectrometry imaging identifies abnormally elevated brain l-DOPA levels and extrastriatal monoaminergic dysregulation in l-DOPA-induced dyskinesia. Sci Adv. 2021 Jan 6;7(2):eabe5948. doi: 10.1126/sciadv.abe5948. Print 2021 Jan.
12 Pharmacokinetics of Levodopa and 3-O-Methyldopa in Parkinsonian Patients Treated with Levodopa and Ropinirole and in Patients with Motor Complications. Pharmaceutics. 2021 Sep 3;13(9):1395. doi: 10.3390/pharmaceutics13091395.

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