Details of the Drug

General Information of Drug (ID: DMN3E57)

• Drug Name: Levodopa
• Synonyms: Levodopa (optimized formulation, Parkinson's disease); More effective levodopa (Parkinson's disease), Orion; Levodopa (optimized formulation, Parkinson's disease), Orion

Indication

Disease Entry	ICD 11	Status	REF
Parkinson disease	8A00.0	Approved	[1]
Parkinsonian disorder	N.A.	Approved	[2]
Postencephalitic Parkinson disease	N.A.	Approved	[2]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 1:
  Molecular Weight (mw); 197.19
  Logarithm of the Partition Coefficient (xlogp); -2.7
  Rotatable Bond Count (rotbonds); 3
  Hydrogen Bond Donor Count (hbonddonor); 4
  Hydrogen Bond Acceptor Count (hbondacc); 5
• ADMET Property:
  Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 0.98 mcg/L [3]
  Absorption Tmax: The time to maximum plasma concentration (Tmax) is 2.2 +/- 1.9 h [3]
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [4]
  Clearance: The clearance of drug is 14.2 mL/min/kg in elderly patients [5]
  Elimination: 0.17% of an orally administered dose is recovered in stool, 0.28% is exhaled, and 78.4% is recovered in urine [6]
  Half-life: The concentration or amount of drug in body reduced by one-half in 2.3 hours []
  Metabolism: The drug is metabolized via the aromatic-L-amino-acid decarboxylase or O-methylated to 3-O-methyldopa by catechol-O-methyltransferase [7]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 674.46844 micromolar/kg/day [8]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.76% [9]
  Vd: The volume of distribution (Vd) of drug is 168 L []
  Water Solubility: The ability of drug to dissolve in water is measured as 1.65 mg/mL [4]

Adverse Drug Reaction (ADR)

ADR Term	Variation	Related DOT	DOT ID	REF
Adverse drug reaction	Not Available	FOS	OTJBUVWS	[10]
Dyskinesias and movement disorders NEC	Not Available	PARK2	OTJBN41W	[10]
Parkinson's disease	Not Available	OGFR	OTROS6RJ	[10]

• Chemical Identifiers:
  Formula: C9H11NO4
  IUPAC Name: (2S)-2-amino-3-(3,4-dihydroxyphenyl)propanoic acid
  Canonical SMILES: C1=CC(=C(C=C1C[C@@H](C(=O)O)N)O)O
  InChI: 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
• Cross-matching ID:
  PubChem CID: 6047
  ChEBI ID: CHEBI:15765
  CAS Number: 59-92-7
  DrugBank ID: DB01235
  TTD ID: D08HVR
  VARIDT ID: DR00125
  INTEDE ID: DR0939
• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Dopamine D2 receptor (D2R)	TTEX248	DRD2_HUMAN	Modulator	[1]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
L-type amino acid transporter 1 (SLC7A5)	DT48T0N	LAT1_HUMAN	Substrate	[11]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[12]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Substrate	[13]
DOPA decarboxylase (DDC)	DETK9CN	DDC_HUMAN	Substrate	[14]
Thiopurine methyltransferase (TPMT)	DEFQ8VO	TPMT_HUMAN	Substrate	[15]
Tyrosine decarboxylase (tdc)	DE3HL9N	TYRDC_ENTFA	Substrate	[16], [17]
Tyrosine decarboxylase (tdc)	DEX2ZLF	TYRDC_LACBR	Substrate	[17]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Aromatic-L-amino-acid decarboxylase (DDC)	OT0TSW09	DDC_HUMAN	Drug Response	[18]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Gene/Protein Processing	[19]
Catechol O-methyltransferase (COMT)	OTPWKTQG	COMT_HUMAN	Biotransformations	[20]
Dopamine beta-hydroxylase (DBH)	OTC6I2SP	DOPO_HUMAN	Gene/Protein Processing	[21]
E3 ubiquitin-protein ligase parkin (PRKN)	OTJBN41W	PRKN_HUMAN	Drug Response	[10]
Homer protein homolog 1 (HOMER1)	OTWFD3SI	HOME1_HUMAN	Drug Response	[22]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Post-Translational Modifications	[23]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Post-Translational Modifications	[23]
Mitogen-activated protein kinase kinase kinase 5 (MAP3K5)	OTQR6ENW	M3K5_HUMAN	Gene/Protein Processing	[19]
Opioid growth factor receptor (OGFR)	OTROS6RJ	OGFR_HUMAN	Drug Response	[10]

Molecular Expression Atlas of This Drug

• The Studied Disease: Parkinson disease
• ICD Disease Classification: 8A00.0

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Dopamine D2 receptor (D2R)	DTT	DRD2	2.50E-02	-0.08	-0.49
P-glycoprotein 1 (ABCB1)	DTP	P-GP	9.39E-02	1.07E-01	2.80E-01
L-type amino acid transporter 1 (SLC7A5)	DTP	LAT1	2.99E-01	1.73E-01	3.72E-01
DOPA decarboxylase (DDC)	DME	DDC	1.35E-03	-7.92E-02	-4.01E-01
Thiopurine methyltransferase (TPMT)	DME	TPMT	1.32E-01	-6.42E-02	-2.31E-01
Cytochrome P450 2D6 (CYP2D6)	DME	CYP2D6	7.30E-01	-1.91E-02	-1.41E-01

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Levodopa

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Disease	REF
Opicapone	DM1BKA6	Moderate	Decreased metabolism of Levodopa caused by Opicapone mediated inhibition of non-CYP450 enzyme.	Parkinsonism [8A00]	[24]
Rasagiline	DM3WKQ4	Moderate	Additive dopaminergic effects by the combination of Levodopa and Rasagiline.	Parkinsonism [8A00]	[25]

Coadministration of a Drug Treating the Disease Different from Levodopa (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Sodium bicarbonate	DMMU6BJ	Minor	Decreased absorption of Levodopa due to altered gastric pH caused by Sodium bicarbonate.	Acidosis [5C73]	[26]
Methylene blue	DMJAPE7	Major	Additive hypertensive effects by the combination of Levodopa and Methylene blue.	Acquired methaemoglobinaemia [3A93]	[27]
Citicoline	DMI4XBM	Minor	Additive dopaminergic effects by the combination of Levodopa and Citicoline.	Cerebral ischaemia [8B1Z]	[28]
Isocarboxazid	DMAF1NB	Major	Additive hypertensive effects by the combination of Levodopa and Isocarboxazid.	Depression [6A70-6A7Z]	[27]
OPC-34712	DMHG57U	Moderate	Additive CNS depression effects by the combination of Levodopa and OPC-34712.	Depression [6A70-6A7Z]	[29]
Clomipramine	DMINRKW	Minor	Altered absorption of Levodopa due to GI dynamics variation caused by Clomipramine.	Depression [6A70-6A7Z]	[30]
Esketamine	DMVU687	Moderate	Additive CNS depression effects by the combination of Levodopa and Esketamine.	Depression [6A70-6A7Z]	[31]
Mepenzolate	DM8YU2F	Moderate	Altered absorption of Levodopa due to GI dynamics variation caused by Mepenzolate.	Digestive system disease [DE2Z]	[32]
Tetrabenazine	DMYWQ0O	Moderate	Antagonize the effect of Levodopa when combined with Tetrabenazine.	Dissociative neurological symptom disorder [6B60]	[33]
Solifenacin	DMG592Q	Moderate	Altered absorption of Levodopa due to GI dynamics variation caused by Solifenacin.	Functional bladder disorder [GC50]	[32]
Brentuximab vedotin	DMWLC57	Moderate	Increased risk of peripheral neuropathy by the combination of Levodopa and Brentuximab vedotin.	Hodgkin lymphoma [2B30]	[34]
Belladonna	DM2RBWK	Moderate	Altered absorption of Levodopa due to GI dynamics variation caused by Belladonna.	Infectious gastroenteritis/colitis [1A40]	[32]
ITI-007	DMUQ1DO	Moderate	Antagonize the effect of Levodopa when combined with ITI-007.	Insomnia [7A00-7A0Z]	[29]
Iron	DMAP8MV	Moderate	Decreased absorption of Levodopa due to formation of complexes caused by Iron.	Iron deficiency anaemia [3A00]	[35]
Allopregnanolone	DMNLHAC	Moderate	Additive CNS depression effects by the combination of Levodopa and Allopregnanolone.	Mental/behavioural/neurodevelopmental disorder [6E20-6E8Z]	[36]
Lasmiditan	DMXLVDT	Moderate	Additive CNS depression effects by the combination of Levodopa and Lasmiditan.	Migraine [8A80]	[37]
Flibanserin	DM70DTN	Moderate	Additive CNS depression effects by the combination of Levodopa and Flibanserin.	Mood disorder [6A60-6E23]	[38]
Ozanimod	DMT6AM2	Major	Additive hypertensive effects by the combination of Levodopa and Ozanimod.	Multiple sclerosis [8A40]	[27]
Methylscopolamine	DM5VWOB	Moderate	Altered absorption of Levodopa due to GI dynamics variation caused by Methylscopolamine.	Peptic ulcer [DA61]	[32]
Levomepromazine	DMIKFEL	Moderate	Antagonize the effect of Levodopa when combined with Levomepromazine.	Psychotic disorder [6A20-6A25]	[29]
Aripiprazole	DM3NUMH	Moderate	Additive hypotensive effects by the combination of Levodopa and Aripiprazole.	Schizophrenia [6A20]	[29]
Iloperidone	DM6AUFY	Moderate	Antagonize the effect of Levodopa when combined with Iloperidone.	Schizophrenia [6A20]	[29]
Paliperidone	DM7NPJS	Moderate	Antagonize the effect of Levodopa when combined with Paliperidone.	Schizophrenia [6A20]	[29]
Molindone	DMAH70G	Moderate	Antagonize the effect of Levodopa when combined with Molindone.	Schizophrenia [6A20]	[29]
Thiothixene	DMDINC4	Moderate	Antagonize the effect of Levodopa when combined with Thiothixene.	Schizophrenia [6A20]	[29]
Amisulpride	DMSJVAM	Major	Antagonize the effect of Levodopa when combined with Amisulpride.	Schizophrenia [6A20]	[31]
Asenapine	DMSQZE2	Moderate	Antagonize the effect of Levodopa when combined with Asenapine.	Schizophrenia [6A20]	[29]
Trimeprazine	DMEMV9D	Moderate	Antagonize the effect of Levodopa when combined with Trimeprazine.	Vasomotor/allergic rhinitis [CA08]	[39]

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