Details of the Drug

General Information of Drug (ID: DMLBVKQ)

Drug Name
Entacapone
Synonyms
Comtan; Comtess; Entacapona; Entacaponum; Novartis brand of entacapone; Orion brand of entacapone; KB475572; OR 611; COM-998; Comtan (TN); Entacapona [INN-Spanish]; Entacapone [USAN:INN]; Entacaponum [INN-Latin]; OR-611; Stalevo (TN); Entacapone (JAN/USAN/INN); N,N-diethyl-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl) acrylamide; (2E)-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)-N,N-diethylprop-2-enamide; (E)-2-Cyano-3-(3,4-dihydroxy-5-nitrophenyl)-N,N-diethyl-2-propenamide; (E)-2-cyano-3-(3,4-dihydroxy-5-nitro-phenyl)-N,N-diethyl-prop-2-enamide; (E)-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)-N,N-diethylprop-2-enamide; (E)-alpha-Cyano-N,N-diethyl-3,4-dihydroxy-5-nitrocinnamamide; 2-Cyano-N,N-diethyl-3-(3,4-dihydroxy-5-nitrophenyl)propenamide
Indication
Disease Entry ICD 11 Status REF
Parkinson disease 8A00.0 Approved [1]
Therapeutic Class
Antiparkinson Agents
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 305.29
Logarithm of the Partition Coefficient (xlogp) 2.1
Rotatable Bond Count (rotbonds) 4
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 6
ADMET Property
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [2]
Bioavailability
The bioavailability of drug is 35% []
Clearance
The clearance of drug is 850 mL/min []
Elimination
0.2% of drug is excreted from urine in the unchanged form [2]
Half-life
The concentration or amount of drug in body reduced by one-half in 0.4 - 0.7 hours [3]
Metabolism
The drug is metabolized via the isomerization to the cis-isomer, followed by direct glucuronidation of the parent and cis-isomer []
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 87.3486 micromolar/kg/day [4]
Unbound Fraction
The unbound fraction of drug in plasma is 0.02% [3]
Vd
The volume of distribution (Vd) of drug is 20 L []
Water Solubility
The ability of drug to dissolve in water is measured as 0.0166 mg/mL [2]
Chemical Identifiers
Formula
C14H15N3O5
IUPAC Name
(E)-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)-N,N-diethylprop-2-enamide
Canonical SMILES
CCN(CC)C(=O)/C(=C/C1=CC(=C(C(=C1)O)O)[N+](=O)[O-])/C#N
InChI
InChI=1S/C14H15N3O5/c1-3-16(4-2)14(20)10(8-15)5-9-6-11(17(21)22)13(19)12(18)7-9/h5-7,18-19H,3-4H2,1-2H3/b10-5+
InChIKey
JRURYQJSLYLRLN-BJMVGYQFSA-N
Cross-matching ID
PubChem CID
5281081
ChEBI ID
CHEBI:4798
CAS Number
130929-57-6
DrugBank ID
DB00494
TTD ID
D0J1VY
VARIDT ID
DR01275
INTEDE ID
DR0581
ACDINA ID
D00231
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Catechol-O-methyl-transferase (COMT) TTKWFB8 COMT_HUMAN Inhibitor [5]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [6]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [7]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
UDP-glucuronosyltransferase 1A9 (UGT1A9)
Main DME 		DE85D2P UD19_HUMAN Substrate [8]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Antileukoproteinase (SLPI) OTUNFUU8 SLPI_HUMAN Gene/Protein Processing [9]
Catechol O-methyltransferase (COMT) OTPWKTQG COMT_HUMAN Gene/Protein Processing [10]
Cystine/glutamate transporter (SLC7A11) OTKJ6PXW XCT_HUMAN Gene/Protein Processing [9]
Glycerol-3-phosphate acyltransferase 1, mitochondrial (GPAM) OTR1XD9B GPAT1_HUMAN Gene/Protein Processing [11]
Hepatocyte growth factor receptor (MET) OT7K55MU MET_HUMAN Gene/Protein Processing [9]
Interleukin-1 alpha (IL1A) OTPSGILV IL1A_HUMAN Gene/Protein Processing [9]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Gene/Protein Processing [9]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Gene/Protein Processing [9]
Proepiregulin (EREG) OTRM4NQY EREG_HUMAN Gene/Protein Processing [9]
Prostaglandin G/H synthase 2 (PTGS2) OT75U9M4 PGH2_HUMAN Gene/Protein Processing [9]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

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
Catechol-O-methyl-transferase (COMT) DTT COMT 9.24E-02 0.17 1.09
Breast cancer resistance protein (ABCG2) DTP BCRP 9.26E-01 -9.37E-02 -1.15E-01
Organic anion transporting polypeptide 1B1 (SLCO1B1) DTP OATP1B1 8.03E-01 8.37E-02 4.07E-01
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Entacapone
DDI Drug Name DDI Drug ID Severity Mechanism Disease REF
Levodopa DMN3E57 Moderate Decreased metabolism of Entacapone caused by Levodopa mediated inhibition of non-CYP450 enzyme. Parkinsonism [8A00] [12]
Dopamine DMPGUCF Moderate Decreased metabolism of Entacapone caused by Dopamine mediated inhibition of non-CYP450 enzyme. Parkinsonism [8A00] [13]
Coadministration of a Drug Treating the Disease Different from Entacapone (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Epinephrine DM3KJBC Moderate Decreased metabolism of Entacapone caused by Epinephrine mediated inhibition of non-CYP450 enzyme. Allergic/hypersensitivity disorder [4A80-4A8Z] [13]
Memantine DMD9WSC Minor Additive dopaminergic effects by the combination of Entacapone and Memantine. Alzheimer disease [8A20] [14]
Isoproterenol DMK7MEY Moderate Decreased metabolism of Entacapone caused by Isoproterenol mediated inhibition of non-CYP450 enzyme. Conduction disorder [BC63] [13]
Olopatadine DMKMWQG Moderate Additive CNS depression effects by the combination of Entacapone and Olopatadine. Conjunctiva disorder [9A60] [15]
Ethanol DMDRQZU Moderate Additive CNS depression effects by the combination of Entacapone and Ethanol. Cystitis [GC00] [15]
OPC-34712 DMHG57U Moderate Additive hypotensive effects by the combination of Entacapone and OPC-34712. Depression [6A70-6A7Z] [16]
Amoxapine DMKITQE Moderate Antagonize the effect of Entacapone when combined with Amoxapine. Depression [6A70-6A7Z] [16]
Esketamine DMVU687 Moderate Additive CNS depression effects by the combination of Entacapone and Esketamine. Depression [6A70-6A7Z] [17]
Dobutamine DMD1B8Z Moderate Decreased metabolism of Entacapone caused by Dobutamine mediated inhibition of non-CYP450 enzyme. Heart failure [BD10-BD1Z] [13]
Methyldopa DM5I621 Moderate Decreased metabolism of Entacapone caused by Methyldopa mediated inhibition of non-CYP450 enzyme. Hypertension [BA00-BA04] [13]
Propiomazine DMKY8V1 Moderate Antagonize the effect of Entacapone when combined with Propiomazine. Insomnia [7A00-7A0Z] [16]
ITI-007 DMUQ1DO Moderate Antagonize the effect of Entacapone when combined with ITI-007. Insomnia [7A00-7A0Z] [16]
Iron DMAP8MV Moderate Decreased absorption of Entacapone due to formation of complexes caused by Iron. Iron deficiency anaemia [3A00] [18]
Allopregnanolone DMNLHAC Moderate Additive CNS depression effects by the combination of Entacapone and Allopregnanolone. Mental/behavioural/neurodevelopmental disorder [6E20-6E8Z] [19]
Lasmiditan DMXLVDT Moderate Additive CNS depression effects by the combination of Entacapone and Lasmiditan. Migraine [8A80] [20]
Flibanserin DM70DTN Moderate Additive CNS depression effects by the combination of Entacapone and Flibanserin. Mood disorder [6A60-6E23] [21]
Thalidomide DM70BU5 Moderate Additive CNS depression effects by the combination of Entacapone and Thalidomide. Multiple myeloma [2A83] [22]
Promethazine DM6I5GR Moderate Additive hypotensive effects by the combination of Entacapone and Promethazine. Nausea/vomiting [MD90] [16]
Metoclopramide DMFA5MY Moderate Additive CNS depression effects by the combination of Entacapone and Metoclopramide. Nausea/vomiting [MD90] [16]
Apraclonidine DMO4PVE Moderate Additive CNS depression effects by the combination of Entacapone and Apraclonidine. Optic nerve disorder [9C40] [23]
Dextropropoxyphene DM23HCX Major Additive CNS depression effects by the combination of Entacapone and Dextropropoxyphene. Pain [MG30-MG3Z] [24]
Levomepromazine DMIKFEL Moderate Antagonize the effect of Entacapone when combined with Levomepromazine. Psychotic disorder [6A20-6A25] [16]
Fluphenazine DMIT8LX Moderate Antagonize the effect of Entacapone when combined with Fluphenazine. Psychotic disorder [6A20-6A25] [16]
Triflupromazine DMKFQJP Moderate Additive hypotensive effects by the combination of Entacapone and Triflupromazine. Psychotic disorder [6A20-6A25] [16]
Quetiapine DM1N62C Moderate Antagonize the effect of Entacapone when combined with Quetiapine. Schizophrenia [6A20] [16]
Mesoridazine DM2ZGAN Moderate Antagonize the effect of Entacapone when combined with Mesoridazine. Schizophrenia [6A20] [16]
Thioridazine DM35M8J Moderate Antagonize the effect of Entacapone when combined with Thioridazine. Schizophrenia [6A20] [16]
Aripiprazole DM3NUMH Moderate Antagonize the effect of Entacapone when combined with Aripiprazole. Schizophrenia [6A20] [16]
Iloperidone DM6AUFY Moderate Antagonize the effect of Entacapone when combined with Iloperidone. Schizophrenia [6A20] [16]
Paliperidone DM7NPJS Moderate Additive CNS depression effects by the combination of Entacapone and Paliperidone. Schizophrenia [6A20] [16]
Haloperidol DM96SE0 Moderate Antagonize the effect of Entacapone when combined with Haloperidol. Schizophrenia [6A20] [16]
Perphenazine DMA4MRX Moderate Additive CNS depression effects by the combination of Entacapone and Perphenazine. Schizophrenia [6A20] [16]
Molindone DMAH70G Moderate Antagonize the effect of Entacapone when combined with Molindone. Schizophrenia [6A20] [16]
Thiothixene DMDINC4 Moderate Antagonize the effect of Entacapone when combined with Thiothixene. Schizophrenia [6A20] [16]
Trifluoperazine DMKBYWI Moderate Antagonize the effect of Entacapone when combined with Trifluoperazine. Schizophrenia [6A20] [16]
Risperidone DMN6DXL Moderate Antagonize the effect of Entacapone when combined with Risperidone. Schizophrenia [6A20] [16]
Amisulpride DMSJVAM Moderate Antagonize the effect of Entacapone when combined with Amisulpride. Schizophrenia [6A20] [16]
Asenapine DMSQZE2 Moderate Antagonize the effect of Entacapone when combined with Asenapine. Schizophrenia [6A20] [16]
Tizanidine DMR2IQ4 Moderate Additive CNS depression effects by the combination of Entacapone and Tizanidine. Tonus and reflex abnormality [MB47] [25]
Methdilazine DMAUHQX Moderate Antagonize the effect of Entacapone when combined with Methdilazine. Vasomotor/allergic rhinitis [CA08] [16]
Trimeprazine DMEMV9D Moderate Antagonize the effect of Entacapone when combined with Trimeprazine. Vasomotor/allergic rhinitis [CA08] [26]
⏷ Show the Full List of 41 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG
DIG Name DIG ID PubChem CID Functional Classification
Mannitol E00103 6251 Diluent; Flavoring agent; Lyophilization aid; Plasticizing agent; Tonicity agent
Quinoline yellow WS E00309 24671 Colorant
Sucralose E00370 71485 Flavoring agent
Sunset yellow FCF E00255 17730 Colorant
Carmellose sodium E00625 Not Available Disintegrant
Eisenoxyd E00585 56841934 Colorant
Ferric hydroxide oxide yellow E00539 23320441 Colorant
Glycerin E00026 753 Antimicrobial preservative; Emollient; Flavoring agent; Humectant; Lubricant; Plasticizing agent; Solvent; Suppository base; Tonicity agent; Viscosity-controlling agent
Hydrogenated polyoxyl 40 castor oil E00662 Not Available Emulsifying agent; Solubilizing agent; Surfactant
Lactose monohydrate E00393 104938 Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate E00208 11177 lubricant
Polysorbate 80 E00665 Not Available Dispersing agent; Emollient; Emulsifying agent; Plasticizing agent; Solubilizing agent; Surfactant; Suspending agent
Povidone E00667 Not Available Binding agent; Coating agent; Disintegrant; Film/membrane-forming agent; Solubilizing agent; Suspending agent
Propylene glycol E00040 1030 Antimicrobial preservative; Humectant; Plasticizing agent; Solvent
Saccharose E00091 5988 Binding agent; Coating agent; Cryoprotectant; Diluent; Flavoring agent; Suspending agent; Viscosity-controlling agent
Silicon dioxide E00670 Not Available Anticaking agent; Opacifying agent; Viscosity-controlling agent
Talc E00520 16211421 Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide E00322 26042 Coating agent; Colorant; Opacifying agent
Triacetin E00080 5541 Humectant; Plasticizing agent; Solvent
Water E00035 962 Solvent
⏷ Show the Full List of 20 Pharmaceutical Excipients of This Drug
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Entacapone 200 mg tablet 200 mg Oral Tablet Oral
Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6647).
2 BDDCS applied to over 900 drugs
3 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
4 Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
5 Entacapone: a catechol-O-methyltransferase inhibitor for the adjunctive treatment of Parkinson's disease. Clin Ther. 2001 Jun;23(6):802-32; discussion 771.
6 Elucidation of the Impact of P-glycoprotein and Breast Cancer Resistance Protein on the Brain Distribution of Catechol-O-Methyltransferase Inhibitors. Drug Metab Dispos. 2017 Dec;45(12):1282-1291.
7 Organic Anion Transporter 2-Mediated Hepatic Uptake Contributes to the Clearance of High-Permeability-Low-Molecular-Weight Acid and Zwitterion Drugs: Evaluation Using 25 Drugs. J Pharmacol Exp Ther. 2018 Nov;367(2):322-334.
8 Kinetic characterization of the 1A subfamily of recombinant human UDP-glucuronosyltransferases. Drug Metab Dispos. 2005 Jul;33(7):1017-26.
9 An in vitro coculture system of human peripheral blood mononuclear cells with hepatocellular carcinoma-derived cells for predicting drug-induced liver injury. Arch Toxicol. 2021 Jan;95(1):149-168. doi: 10.1007/s00204-020-02882-4. Epub 2020 Aug 20.
10 Beneficial effects of natural phenolics on levodopa methylation and oxidative neurodegeneration. Brain Res. 2013 Feb 25;1497:1-14. doi: 10.1016/j.brainres.2012.11.043. Epub 2012 Dec 1.
11 Effect of the Catechol-O-Methyltransferase Inhibitors Tolcapone and Entacapone on Fatty Acid Metabolism in HepaRG Cells. Toxicol Sci. 2018 Aug 1;164(2):477-488.
12 Dingemanse J, Jorga K, Zurcher G, Schmitt M, Sedek G, Da Prada M, Van Brummelen P "Pharmacokinetic-pharmacodynamic interaction between the COMT inhibitor tolcapone and single-dose levodopa." Br J Clin Pharmacol 40 (1995): 253-62. [PMID: 8527287]
13 Illi A, Sundberg S, Ojala-Karlsson P, Korhonen P, Scheinin M, Gordin A "The effect of entacapone on the disposition and hemodynamic effects of intravenous isoproterenol and epinephrine." Clin Pharmacol Ther 58 (1995): 221-7. [PMID: 7648772]
14 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
15 Warrington SJ, Ankier SI, Turner P "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology 15 (1986): 31-7. [PMID: 3725002]
16 Mims RB, Scott CL, Modebe O, Bethune JE "Inhibition of L-dopa-induced growth hormone stimulation by pyridoxine and chlorpromazine." J Clin Endocrinol Metab 40 (1975): 256-9. [PMID: 1117978]
17 Cerner Multum, Inc. "Australian Product Information.".
18 Product Information. Comtan (entacapone) Novartis Pharmaceuticals, East Hanover, NJ.
19 Product Information. Zulresso (brexanolone). Sage Therapeutics, Inc., Cambridge, MA.
20 Product Information. Reyvow (lasmiditan). Lilly, Eli and Company, Indianapolis, IN.
21 Product Information. Addyi (flibanserin). Sprout Pharmaceuticals, Raleigh, NC.
22 Product Information. Thalomid (thalidomide). Celgene Corporation, Warren, NJ.
23 Product Information. Alphagan (brimonidine ophthalmic). Allergan Inc, Irvine, CA.
24 Hansen BS, Dam M, Brandt J, et al "Influence of dextropropoxyphene on steady state serum levels and protein binding of three anti-epileptic drugs in man." Acta Neurol Scand 61 (1980): 357-67. [PMID: 6998251]
25 Product Information. Zanaflex (tizanidine). Acorda Therapeutics, Hawthorne, NY.
26 Product Information. Norprolac (quinagolide). Ferring Inc, North York, IA.