You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Human Metabolome Database.

NOTICE: The ontology section is undergoing maintainance. If it is not visible on a metabocard page or does not include the expected information, please try again later! Thank you!

Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:51 UTC
Update Date2017-12-20 20:31:00 UTC
HMDB IDHMDB0015158
Secondary Accession Numbers
  • HMDB15158
Metabolite Identification
Common NameFelodipine
DescriptionFelodipine is a long-acting 1,4-dihydropyridine calcium channel blocker (CCB)b. It acts primarily on vascular smooth muscle cells by stabilizing voltage-gated L-type calcium channels in their inactive conformation. By inhibiting the influx of calcium in smooth muscle cells, felodipine prevents calcium-dependent myocyte contraction and vasoconstriction. Felodipine is the most potent CCB in use and is unique in that it exhibits fluorescent activity. In addition to binding to L-type calcium channels, felodipine binds to a number of calcium-binding proteins, exhibits competitive antagonism of the mineralcorticoid receptor, inhibits the activity of calmodulin-dependent cyclic nucleotide phosphodiesterase, and blocks calcium influx through voltage-gated T-type calcium channels. Felodipine is used to treat mild to moderate essential hypertension.
Structure
Thumb
Synonyms
ValueSource
(+-)-Ethyl methyl 4-(2,3-dichlorophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylateChEBI
3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylateChEBI
4-(2,3-Dichlorophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic acid ethyl methyl esterChEBI
FelodipinaChEBI
FelodipinumChEBI
(+-)-Ethyl methyl 4-(2,3-dichlorophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic acidGenerator
3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylic acidGenerator
4-(2,3-Dichlorophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate ethyl methyl esterGenerator
DL-FelodipineHMDB
1a Brand OF felodipineMeSH
Alpharma brand OF felodipineMeSH
AstraZeneca brand OF felodipineMeSH
Azupharma brand OF felodipineMeSH
felo BiochemieMeSH
felo PurenMeSH
FelobetaMeSH
FelodurMeSH
Heumann brand OF felodipineMeSH
Hoechst brand OF felodipineMeSH
Pharmacia spain brand OF felodipineMeSH
TheraPharm brand OF felodipineMeSH
felo-PurenMeSH
FelocorMeSH
Felodipin heumannMeSH
Felodipin stadaMeSH
Felodipin duraMeSH
MunobalMeSH
Pharmaceutica astra brand OF felodipineMeSH
Wörwag brand OF felodipineMeSH
CT Arzneimittel brand OF felodipineMeSH
CT-Arzneimittel brand OF felodipineMeSH
Aliud brand OF felodipineMeSH
Alphapharm brand OF felodipineMeSH
Astra brand OF felodipineMeSH
BC Brand OF felodipineMeSH
Felodipin alMeSH
Felodipin azuMeSH
Felodipin ratiopharmMeSH
Merck dura brand OF felodipineMeSH
PerfudalMeSH
PlendilMeSH
Promed brand OF felodipineMeSH
Stadapharm brand OF felodipineMeSH
Betapharm brand OF felodipineMeSH
Felodipin von CTMeSH
AbZ brand OF felodipineMeSH
AgonMeSH
Aventis brand OF felodipineMeSH
Felodipin 1a pharmaMeSH
Felodipin abzMeSH
Felodipin-ratiopharmMeSH
FelogammaMeSH
FenselMeSH
FlodilMeSH
Heumann, felodipinMeSH
Hexal brand OF felodipineMeSH
ModipMeSH
RenedilMeSH
Ratiopharm brand OF felodipineMeSH
Chemical FormulaC18H19Cl2NO4
Average Molecular Weight384.254
Monoisotopic Molecular Weight383.069113515
IUPAC Name3-ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate
Traditional Namefelodipine
CAS Registry Number72509-76-3
SMILES
CCOC(=O)C1=C(C)NC(C)=C(C1C1=C(Cl)C(Cl)=CC=C1)C(=O)OC
InChI Identifier
InChI=1S/C18H19Cl2NO4/c1-5-25-18(23)14-10(3)21-9(2)13(17(22)24-4)15(14)11-7-6-8-12(19)16(11)20/h6-8,15,21H,5H2,1-4H3
InChI KeyRZTAMFZIAATZDJ-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as dihydropyridinecarboxylic acids and derivatives. These are compounds containing a dihydropyridine moiety bearing a carboxylic acid group.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassPyridines and derivatives
Sub ClassHydropyridines
Direct ParentDihydropyridinecarboxylic acids and derivatives
Alternative Parents
Substituents
  • Dihydropyridinecarboxylic acid derivative
  • 1,2-dichlorobenzene
  • Chlorobenzene
  • Halobenzene
  • Aryl chloride
  • Aryl halide
  • Monocyclic benzene moiety
  • Dicarboxylic acid or derivatives
  • Benzenoid
  • Vinylogous amide
  • Alpha,beta-unsaturated carboxylic ester
  • Enoate ester
  • Methyl ester
  • Amino acid or derivatives
  • Carboxylic acid ester
  • Carboxylic acid derivative
  • Secondary aliphatic amine
  • Enamine
  • Secondary amine
  • Azacycle
  • Organonitrogen compound
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organic oxide
  • Amine
  • Organohalogen compound
  • Carbonyl group
  • Organopnictogen compound
  • Organic oxygen compound
  • Organic nitrogen compound
  • Organochloride
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Ontology
Process

Naturally occurring process:

  Biological process:

    Biochemical pathway:

Disposition

Biological location:

  Subcellular:

  Biofluid and excreta:

Role

Industrial application:

  Pharmaceutical industry:

    Cardiovascular drug:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point145 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.0072 g/LNot Available
LogP3.8Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0072 g/LALOGPS
logP4.36ALOGPS
logP3.44ChemAxon
logS-4.7ALOGPS
pKa (Strongest Basic)5.39ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area64.63 ŲChemAxon
Rotatable Bond Count6ChemAxon
Refractivity99.2 m³·mol⁻¹ChemAxon
Polarizability38.04 ųChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-01t9-3009000000-5b611cdc2d075de69610View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-000j-0922000000-9b26b987caa87b8a13afView in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0udu-0139000000-085071c20c5d0c134d8fView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-001r-0019000000-33bf0db3bf36f29993fbView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0fe0-0095000000-c27a529dc8d62e0c3663View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-004i-0490000000-b027fd5c39a74d5a8983View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-001i-0009000000-74fea585f5eab97e301dView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-01q9-0029000000-611d97581685b1d82833View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0wbc-1095000000-178af93061f6d2ad0db1View in MoNA
Biological Properties
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
Pathways
NameSMPDB/PathwhizKEGG
Felodipine Action PathwayPw000392Pw000392 greyscalePw000392 simpleNot Available
Felodipine Metabolism PathwayPw000595Pw000595 greyscalePw000595 simpleNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01023 details
UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01023 details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB01023
Phenol Explorer Compound IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID3216
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkFelodipine
METLIN IDNot Available
PubChem Compound3333
PDB IDNot Available
ChEBI ID585948
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Dunselman PH, Edgar B: Felodipine clinical pharmacokinetics. Clin Pharmacokinet. 1991 Dec;21(6):418-30. [PubMed:1782737 ]

Only showing the first 10 proteins. There are 20 proteins in total.

Enzymes

General function:
Involved in catalytic activity
Specific function:
Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes. Has a higher affinity for cGMP than for cAMP.
Gene Name:
PDE1A
Uniprot ID:
P54750
Molecular weight:
61251.38
References
  1. Lamers JM, Cysouw KJ, Verdouw PD: Slow calcium channel blockers and calmodulin. Effect of felodipine, nifedipine, prenylamine and bepridil on cardiac sarcolemmal calcium pumping ATPase. Biochem Pharmacol. 1985 Nov 1;34(21):3837-43. [PubMed:2933041 ]
  2. Sharma RK, Wang JH, Wu Z: Mechanisms of inhibition of calmodulin-stimulated cyclic nucleotide phosphodiesterase by dihydropyridine calcium antagonists. J Neurochem. 1997 Aug;69(2):845-50. [PubMed:9231746 ]
General function:
Involved in catalytic activity
Specific function:
Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes. Has a preference for cGMP as a substrate.
Gene Name:
PDE1B
Uniprot ID:
Q01064
Molecular weight:
61379.235
References
  1. Lamers JM, Cysouw KJ, Verdouw PD: Slow calcium channel blockers and calmodulin. Effect of felodipine, nifedipine, prenylamine and bepridil on cardiac sarcolemmal calcium pumping ATPase. Biochem Pharmacol. 1985 Nov 1;34(21):3837-43. [PubMed:2933041 ]
  2. Sharma RK, Wang JH, Wu Z: Mechanisms of inhibition of calmodulin-stimulated cyclic nucleotide phosphodiesterase by dihydropyridine calcium antagonists. J Neurochem. 1997 Aug;69(2):845-50. [PubMed:9231746 ]
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular weight:
57255.585
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
  2. Galetin A, Clarke SE, Houston JB: Quinidine and haloperidol as modifiers of CYP3A4 activity: multisite kinetic model approach. Drug Metab Dispos. 2002 Dec;30(12):1512-22. [PubMed:12433827 ]
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular weight:
55627.365
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
General function:
Involved in monooxygenase activity
Specific function:
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular weight:
55768.94
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP3A5
Uniprot ID:
P20815
Molecular weight:
57108.065
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP3A7
Uniprot ID:
P24462
Molecular weight:
57525.03
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti-cancer drug paclitaxel (taxol).
Gene Name:
CYP2C8
Uniprot ID:
P10632
Molecular weight:
55824.275
References
  1. Schoch GA, Yano JK, Sansen S, Dansette PM, Stout CD, Johnson EF: Determinants of cytochrome P450 2C8 substrate binding: structures of complexes with montelukast, troglitazone, felodipine, and 9-cis-retinoic acid. J Biol Chem. 2008 Jun 20;283(25):17227-37. doi: 10.1074/jbc.M802180200. Epub 2008 Apr 15. [PubMed:18413310 ]
  2. Walsky RL, Gaman EA, Obach RS: Examination of 209 drugs for inhibition of cytochrome P450 2C8. J Clin Pharmacol. 2005 Jan;45(1):68-78. [PubMed:15601807 ]
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
General function:
Involved in calcium ion binding
Specific function:
Calmodulin mediates the control of a large number of enzymes and other proteins by Ca(2+). Among the enzymes to be stimulated by the calmodulin-Ca(2+) complex are a number of protein kinases and phosphatases. Together with CEP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis
Gene Name:
CALM1
Uniprot ID:
P62158
Molecular weight:
16837.5
References
  1. Bostrom SL, Westerlund C, Rochester S, Vogel HJ: Binding of a dihydropyridine felodipine-analogue to calmodulin and related calcium-binding proteins. Biochem Pharmacol. 1988 Oct 1;37(19):3723-8. [PubMed:3178884 ]
  2. Johnson JD, Andrews CT, Khabbaza EJ, Mills JS: The interaction of felodipine with calcium-binding proteins. J Cardiovasc Pharmacol. 1987;10 Suppl 1:S53-9. [PubMed:2442519 ]
  3. Lamers JM, Cysouw KJ, Verdouw PD: Slow calcium channel blockers and calmodulin. Effect of felodipine, nifedipine, prenylamine and bepridil on cardiac sarcolemmal calcium pumping ATPase. Biochem Pharmacol. 1985 Nov 1;34(21):3837-43. [PubMed:2933041 ]
  4. Lamers JM, Verdouw PD, Mas-Oliva J: The effects of felodipine and bepridil on calcium-stimulated calmodulin binding and calcium pumping ATPase of cardiac sarcolemma before and after removal of endogenous calmodulin. Mol Cell Biochem. 1987 Dec;78(2):169-76. [PubMed:2964559 ]
  5. Mills JS, Bailey BL, Johnson JD: Cooperativity among calmodulin's drug binding sites. Biochemistry. 1985 Aug 27;24(18):4897-902. [PubMed:4074665 ]
  6. Walsh MP, Sutherland C, Scott-Woo GC: Effects of felodipine (a dihydropyridine calcium channel blocker) and analogues on calmodulin-dependent enzymes. Biochem Pharmacol. 1988 Apr 15;37(8):1569-80. [PubMed:2833901 ]
General function:
Involved in ion channel activity
Specific function:
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1D gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin- GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA)
Gene Name:
CACNA1D
Uniprot ID:
Q01668
Molecular weight:
245138.8
References
  1. Sinnegger-Brauns MJ, Huber IG, Koschak A, Wild C, Obermair GJ, Einzinger U, Hoda JC, Sartori SB, Striessnig J: Expression and 1,4-dihydropyridine-binding properties of brain L-type calcium channel isoforms. Mol Pharmacol. 2009 Feb;75(2):407-14. doi: 10.1124/mol.108.049981. Epub 2008 Nov 24. [PubMed:19029287 ]

Transporters

General function:
Involved in ATP binding
Specific function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular weight:
141477.3
References
  1. Wang EJ, Casciano CN, Clement RP, Johnson WW: Active transport of fluorescent P-glycoprotein substrates: evaluation as markers and interaction with inhibitors. Biochem Biophys Res Commun. 2001 Nov 30;289(2):580-5. [PubMed:11716514 ]

Only showing the first 10 proteins. There are 20 proteins in total.