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Identification
NameFelodipine
Accession NumberDB01023  (APRD00374)
Typesmall molecule
Groupsapproved, investigational
Description

Felodipine 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
SynonymLanguageCode
FelodipinaSpanishINN
FelodipineNot AvailableINN, BAN, USAN
FelodipinumLatinINN
SaltsNot Available
Brand names
NameCompany
Felodur ERNot Available
FelogardNot Available
PenedilNot Available
PlendilAstraZeneca
Plendil DepottabAstraZeneca
Plendil ERAstraZeneca
Plendil RetardAstraZeneca
RenedilSanofi-Aventis
SplendilNot Available
Brand mixtures
Brand NameIngredients
Lexxelfelodipine + enalapril maleate
Categories
CAS number72509-76-3
WeightAverage: 384.254
Monoisotopic: 383.069113515
Chemical FormulaC18H19Cl2NO4
InChI KeyRZTAMFZIAATZDJ-UHFFFAOYSA-N
InChI
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
IUPAC Name
3-ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate
SMILES
CCOC(=O)C1=C(C)NC(C)=C(C1C1=C(Cl)C(Cl)=CC=C1)C(=O)OC
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassPyridines and Derivatives
SubclassHydropyridines
Direct parentDihydropyridinecarboxylic Acids and Derivatives
Alternative parentsDichlorobenzenes; Aryl Chlorides; Dicarboxylic Acids and Derivatives; Carboxylic Acid Esters; Enamines; Enolates; Polyamines; Ethers; Organochlorides
Substituents1,2-dichlorobenzene; chlorobenzene; aryl halide; benzene; dicarboxylic acid derivative; aryl chloride; carboxylic acid ester; enamine; carboxylic acid derivative; polyamine; ether; enolate; organochloride; organonitrogen compound; organohalogen
Classification descriptionThis compound belongs to the dihydropyridinecarboxylic acids and derivatives. These are compounds containing a dihydropyridine moiety bearing a carboxylic acid group.
Pharmacology
IndicationFor the treatment of mild to moderate essential hypertension.
PharmacodynamicsFelodipine belongs to the dihydropyridine (DHP) class of calcium channel blockers (CCBs), the most widely used class of CCBs. There are at least five different types of calcium channels in Homo sapiens: L-, N-, P/Q-, R- and T-type. It was widely accepted that CCBs target L-type calcium channels, the major channel in muscle cells that mediates contraction; however, some studies have shown that felodipine also binds to and inhibits T-type calcium channels. T-type calcium channels are most commonly found on neurons, cells with pacemaker activity and on osteocytes. The pharmacologic significance of T-type calcium channel blockade is unknown. Felodipine also binds to calmodulin and inhibits calmodulin-dependent calcium release from the sarcoplasmic reticulum. The effect of this interaction appears to be minor. Another study demonstrated that felodipine attenuates the activity of calmodulin-dependent cyclic nucleotide phosphodiesterase (CaMPDE) by binding to the PDE-1B1 and PDE-1A2 enzyme subunits. CaMPDE is one of the key enzymes involved in cyclic nucleotides and calcium second messenger systems. Felodipine also acts as an antagonist to the mineralcorticoid receptor by competing with aldosterone for binding and blocking aldosterone-induced coactivator recruitment of the mineralcorticoid receptor. Felodipine is able to bind to skeletal and cardiac muscle isoforms of troponin C, one of the key regulatory proteins in muscle contraction. Though felodipine exhibits binding to many endogenous molecules, its vasodilatory effects are still thought to be brought about primarily through inhibition of voltage-gated L-type calcium channels. Similar to other DHP CCBs, felodipine binds directly to inactive calcium channels stabilizing their inactive conformation. Since arterial smooth muscle depolarizations are longer in duration than cardiac muscle depolarizations, inactive channels are more prevalent in smooth muscle cells. Alternative splicing of the alpha-1 subunit of the channel gives felodipine additional arterial selectivity. At therapeutic sub-toxic concentrations, felodipine has little effect on cardiac myocytes and conduction cells.
Mechanism of actionFelodipine decreases arterial smooth muscle contractility and subsequent vasoconstriction by inhibiting the influx of calcium ions through voltage-gated L-type calcium channels. It reversibly competes against nitrendipine and other DHP CCBs for DHP binding sites in vascular smooth muscle and cultured rabbit atrial cells. Calcium ions entering the cell through these channels bind to calmodulin. Calcium-bound calmodulin then binds to and activates myosin light chain kinase (MLCK). Activated MLCK catalyzes the phosphorylation of the regulatory light chain subunit of myosin, a key step in muscle contraction. Signal amplification is achieved by calcium-induced calcium release from the sarcoplasmic reticulum through ryanodine receptors. Inhibition of the initial influx of calcium decreases the contractile activity of arterial smooth muscle cells and results in vasodilation. The vasodilatory effects of felodipine result in an overall decrease in blood pressure. Felodipine may be used to treat mild to moderate essential hypertension.
AbsorptionIs completely absorbed from the gastrointestinal tract; however, extensive first-pass metabolism through the portal circulation results in a low systemic availability of 15%. Bioavailability is unaffected by food.
Volume of distribution
  • 10 L/kg
Protein binding99%, primarily to the albumin fraction.
Metabolism

Hepatic metabolism primarily via cytochrome P450 3A4. Six metabolites with no appreciable vasodilatory effects have been identified.

SubstrateEnzymesProduct
Felodipine
dehydrofelodipineDetails
Route of eliminationAlthough higher concentrations of the metabolites are present in the plasma due to decreased urinary excretion, these are inactive. Animal studies have demonstrated that felodipine crosses the blood-brain barrier and the placenta.
Half life17.5-31.5 hours in hypertensive patients; 19.1-35.9 hours in elderly hypertensive patients; 8.5-19.7 in healthy volunteers.
Clearance
  • 0.8 L/min [Young healthy subjects]
ToxicitySymptoms of overdose include excessive peripheral vasodilation with marked hypotension and possibly bradycardia. Oral rat LD50 is 1050 mg/kg.
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Felodipine Action PathwayDrug actionSMP00377
Felodipine Metabolism PathwayDrug metabolismSMP00619
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9878
Blood Brain Barrier - 0.83
Caco-2 permeable + 0.8867
P-glycoprotein substrate Substrate 0.5149
P-glycoprotein inhibitor I Inhibitor 0.8563
P-glycoprotein inhibitor II Non-inhibitor 0.8383
Renal organic cation transporter Non-inhibitor 0.8664
CYP450 2C9 substrate Non-substrate 0.8357
CYP450 2D6 substrate Non-substrate 0.9116
CYP450 3A4 substrate Substrate 0.6954
CYP450 1A2 substrate Inhibitor 0.9106
CYP450 2C9 substrate Inhibitor 0.8948
CYP450 2D6 substrate Non-inhibitor 0.9232
CYP450 2C19 substrate Inhibitor 0.8994
CYP450 3A4 substrate Inhibitor 0.7959
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.9304
Ames test Non AMES toxic 0.7849
Carcinogenicity Non-carcinogens 0.7511
Biodegradation Not ready biodegradable 0.9527
Rat acute toxicity 2.4526 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9455
hERG inhibition (predictor II) Non-inhibitor 0.8734
Pharmacoeconomics
Manufacturers
  • Mutual pharmaceutical co inc
  • Mylan pharmaceuticals inc
  • Astrazeneca pharmaceuticals lp
Packagers
Dosage forms
FormRouteStrength
Tablet, extended releaseOral10 mg
Tablet, extended releaseOral2.5 mg
Tablet, extended releaseOral5 mg
Prices
Unit descriptionCostUnit
Plendil 10 mg 24 Hour tablet3.17USDtablet
Plendil er 10 mg tablet3.05USDtablet
Plendil 10 mg tablet sa2.96USDtablet
Felodipine 10 mg 24 Hour tablet2.95USDtablet
Plendil er 2.5 mg tablet2.94USDtablet
Felodipine er 10 mg tablet2.72USDtablet
Plendil er 5 mg tablet2.6USDtablet
Plendil 5 mg 24 Hour tablet1.77USDtablet
Plendil 2.5 mg 24 Hour tablet1.76USDtablet
Felodipine 5 mg 24 Hour tablet1.67USDtablet
Plendil 2.5 mg tablet sa1.65USDtablet
Plendil 5 mg tablet sa1.65USDtablet
Felodipine 2.5 mg 24 Hour tablet1.57USDtablet
Felodipine er 2.5 mg tablet1.51USDtablet
Felodipine er 5 mg tablet1.51USDtablet
Renedil 10 mg Extended-Release Tablet1.22USDtablet
Plendil 10 mg Extended-Release Tablet1.15USDtablet
Renedil 5 mg Extended-Release Tablet0.81USDtablet
Plendil 5 mg Extended-Release Tablet0.77USDtablet
Sandoz Felodipine 10 mg Extended-Release Tablet0.73USDtablet
Renedil 2.5 mg Extended-Release Tablet0.6USDtablet
Plendil 2.5 mg Extended-Release Tablet0.57USDtablet
Sandoz Felodipine 5 mg Extended-Release Tablet0.48USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point145 ┬░CNot Available
water solubility19.7 mg/LNot Available
logP3.86SANGSTER (1994)
Caco2 permeability-4.64ADME Research, USCD
Predicted Properties
PropertyValueSource
water solubility7.15e-03 g/lALOGPS
logP4.36ALOGPS
logP3.44ChemAxon
logS-4.7ALOGPS
pKa (strongest basic)5.39ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count3ChemAxon
hydrogen donor count1ChemAxon
polar surface area64.63ChemAxon
rotatable bond count6ChemAxon
refractivity99.2ChemAxon
polarizability38.04ChemAxon
number of rings2ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Vinay Sharma, “Preparation of micron-size felodipine particles by microfluidization.” U.S. Patent US20020086061, issued July 04, 2002.

US20020086061
General Reference
  1. Dunselman PH, Edgar B: Felodipine clinical pharmacokinetics. Clin Pharmacokinet. 1991 Dec;21(6):418-30. Pubmed
External Links
ResourceLink
KEGG DrugD00319
PubChem Compound3333
PubChem Substance46506968
ChemSpider3216
BindingDB50017710
ChEBI585948
ChEMBLCHEMBL1480
Therapeutic Targets DatabaseDAP000487
PharmGKBPA449591
IUPHAR4190
Guide to Pharmacology4190
Drug Product Database2222000
RxListhttp://www.rxlist.com/cgi/generic2/felo.htm
Drugs.comhttp://www.drugs.com/cdi/felodipine.html
PDRhealthhttp://www.pdrhealth.com/drugs/rx/rx-mono.aspx?contentFileName=ple1339.html&contentName=Plendil&contentId=593
WikipediaFelodipine
ATC CodesC08CA02
AHFS Codes
  • 24:28.08
PDB EntriesNot Available
FDA labelshow(228 KB)
MSDSshow(55.4 KB)
Interactions
Drug Interactions
Drug
AmobarbitalThe barbiturate, amobarbital, decreases the effect of felodipine.
AprobarbitalThe barbiturate, aprobarbital, decreases the effect of felodipine.
ButabarbitalThe barbiturate, butabarbital, decreases the effect of felodipine.
ButalbitalThe barbiturate, butalbital, decreases the effect of felodipine.
ButethalThe barbiturate, butethal, decreases the effect of felodipine.
CarbamazepineCarbamazepine may increase the metabolism of felodipine. Monitor for changes in the therapeutic and adverse effects of felodipine if carbamazepine is initiated, discontinued or dose changed.
Dihydroquinidine barbiturateThe barbiturate, dihydroquinidine barbiturate, decreases the effect of felodipine.
ErythromycinErythromycin increases the effect of felodipine
EthotoinThe hydantoin decreases the effect of felodipine
FosphenytoinThe hydantoin decreases the effect of felodipine
HeptabarbitalThe barbiturate, heptabarbital, decreases the effect of felodipine.
HexobarbitalThe barbiturate, hexobarbital, decreases the effect of felodipine.
ItraconazoleItraconazole may increase the therapeutic and adverse effects of felodipine.
JosamycinErythromycin increases the effect of felodipine
MephenytoinThe hydantoin decreases the effect of felodipine
MethohexitalThe barbiturate, methohexital, decreases the effect of felodipine.
MethylphenobarbitalThe barbiturate, methylphenobarbital, decreases the effect of felodipine.
NelfinavirNelfinavir increases the effect and toxicity of felodipine
OxcarbazepineOxcarbazepine decreases the levels of felodipine
PentobarbitalThe barbiturate, pentobarbital, decreases the effect of felodipine.
PhenobarbitalThe barbiturate, phenobarbital, decreases the effect of felodipine.
PhenytoinThe hydantoin decreases the effect of felodipine
PrimidoneThe barbiturate, primidone, decreases the effect of felodipine.
Quinidine barbiturateThe barbiturate, quinidine barbiturate, decreases the effect of felodipine.
QuinupristinThis combination presents an increased risk of toxicity
SecobarbitalThe barbiturate, secobarbital, decreases the effect of felodipine.
TacrolimusFelodipine increases tacrolimus levels
TalbutalThe barbiturate, talbutal, decreases the effect of felodipine.
TelithromycinTelithromycin may reduce clearance of Felodipine. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Felodipine if Telithromycin is initiated, discontinued or dose changed.
ThiopentalThe CYP3A4 inducer, Thiopental, may increase the metabolism and clearance of Felodipine, a CYP3A4 substrate. Monitor for changes in the therapeutic/adverse effects of Felodipine if Thiopental is initiated, discontinued or dose changed.
TipranavirTipranavir, co-administered with Ritonavir, may alter the concentration of Felopidine. Monitor for efficacy and adverse/toxic effects of Felopidine.
TreprostinilAdditive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
TretinoinThe moderate CYP2C8 inhibitor, Felopidine, may decrease the metabolism and clearance of oral Tretinoin. Monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Felopidine is initiated, discontinued to dose changed.
VoriconazoleVoriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of felodipine by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of felodipine if voriconazole is initiated, discontinued or dose changed.
Food Interactions
  • Grapefruit down regulates post-translational expression of CYP3A4, the major metabolizing enzyme of nifedipine. Grapefruit, in all forms (e.g. whole fruit, juice and rind), can significantly increase serum levels of nifedipine and may cause toxicity. Avoid grapefruit products while on this medication.
  • Take without regard to meals.

Targets

1. Voltage-dependent L-type calcium channel subunit alpha-1C

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Voltage-dependent L-type calcium channel subunit alpha-1C Q13936 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Furukawa T, Yamakawa T, Midera T, Sagawa T, Mori Y, Nukada T: Selectivities of dihydropyridine derivatives in blocking Ca(2+) channel subtypes expressed in Xenopus oocytes. J Pharmacol Exp Ther. 1999 Nov;291(2):464-73. Pubmed
  3. Striessnig, J. (2004). Ca 2+ channel blockers. In S. Offermanns, & W. Rosenthal (Eds.). Encyclopedic reference of molecular pharmacology (pp. 201-207). Berlin, Germany: Springer.
  4. Zahradnikova A, Minarovic I, Zahradnik I: Competitive and cooperative effects of Bay K8644 on the L-type calcium channel current inhibition by calcium channel antagonists. J Pharmacol Exp Ther. 2007 Aug;322(2):638-45. Epub 2007 May 2. Pubmed

2. Voltage-dependent calcium channel subunit alpha-2/delta-1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Voltage-dependent calcium channel subunit alpha-2/delta-1 P54289 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Furukawa T, Yamakawa T, Midera T, Sagawa T, Mori Y, Nukada T: Selectivities of dihydropyridine derivatives in blocking Ca(2+) channel subtypes expressed in Xenopus oocytes. J Pharmacol Exp Ther. 1999 Nov;291(2):464-73. Pubmed
  3. Striessnig, J. (2004). Ca 2+ channel blockers. In S. Offermanns, & W. Rosenthal (Eds.). Encyclopedic reference of molecular pharmacology (pp. 201-207). Berlin, Germany: Springer.
  4. Zahradnikova A, Minarovic I, Zahradnik I: Competitive and cooperative effects of Bay K8644 on the L-type calcium channel current inhibition by calcium channel antagonists. J Pharmacol Exp Ther. 2007 Aug;322(2):638-45. Epub 2007 May 2. Pubmed

3. Voltage-dependent L-type calcium channel subunit beta-2

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Voltage-dependent L-type calcium channel subunit beta-2 Q08289 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Furukawa T, Yamakawa T, Midera T, Sagawa T, Mori Y, Nukada T: Selectivities of dihydropyridine derivatives in blocking Ca(2+) channel subtypes expressed in Xenopus oocytes. J Pharmacol Exp Ther. 1999 Nov;291(2):464-73. Pubmed
  3. Striessnig, J. (2004). Ca 2+ channel blockers. In S. Offermanns, & W. Rosenthal (Eds.). Encyclopedic reference of molecular pharmacology (pp. 201-207). Berlin, Germany: Springer.
  4. Zahradnikova A, Minarovic I, Zahradnik I: Competitive and cooperative effects of Bay K8644 on the L-type calcium channel current inhibition by calcium channel antagonists. J Pharmacol Exp Ther. 2007 Aug;322(2):638-45. Epub 2007 May 2. Pubmed

4. Voltage-dependent L-type calcium channel subunit alpha-1D

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Voltage-dependent L-type calcium channel subunit alpha-1D Q01668 Details

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. Epub 2008 Nov 24. Pubmed

5. Voltage-dependent L-type calcium channel subunit alpha-1S

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Voltage-dependent L-type calcium channel subunit alpha-1S Q13698 Details

References:

  1. Peterson BZ, Catterall WA: Allosteric interactions required for high-affinity binding of dihydropyridine antagonists to Ca(V)1.1 Channels are modulated by calcium in the pore. Mol Pharmacol. 2006 Aug;70(2):667-75. Epub 2006 May 4. Pubmed

6. Voltage-dependent T-type calcium channel subunit alpha-1H

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Voltage-dependent T-type calcium channel subunit alpha-1H O95180 Details

References:

  1. Cohen CJ, Spires S, Van Skiver D: Block of T-type Ca channels in guinea pig atrial cells by antiarrhythmic agents and Ca channel antagonists. J Gen Physiol. 1992 Oct;100(4):703-28. Pubmed
  2. Perez-Reyes E, Van Deusen AL, Vitko I: Molecular pharmacology of human Cav3.2 T-type Ca2+ channels: block by antihypertensives, antiarrhythmics, and their analogs. J Pharmacol Exp Ther. 2009 Feb;328(2):621-7. Epub 2008 Oct 30. Pubmed

7. Voltage-dependent calcium channel subunit alpha-2/delta-2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Voltage-dependent calcium channel subunit alpha-2/delta-2 Q9NY47 Details

References:

  1. Cohen CJ, Spires S, Van Skiver D: Block of T-type Ca channels in guinea pig atrial cells by antiarrhythmic agents and Ca channel antagonists. J Gen Physiol. 1992 Oct;100(4):703-28. Pubmed
  2. Perez-Reyes E, Van Deusen AL, Vitko I: Molecular pharmacology of human Cav3.2 T-type Ca2+ channels: block by antihypertensives, antiarrhythmics, and their analogs. J Pharmacol Exp Ther. 2009 Feb;328(2):621-7. Epub 2008 Oct 30. Pubmed

8. Calmodulin

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: other

Components

Name UniProt ID Details
Calmodulin P62158 Details

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
  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
  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
  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
  5. Mills JS, Bailey BL, Johnson JD: Cooperativity among calmodulin’s drug binding sites. Biochemistry. 1985 Aug 27;24(18):4897-902. Pubmed
  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

9. Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B Q01064 Details

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
  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

10. Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A P54750 Details

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
  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

11. Mineralocorticoid receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Mineralocorticoid receptor P08235 Details

References:

  1. Dietz JD, Du S, Bolten CW, Payne MA, Xia C, Blinn JR, Funder JW, Hu X: A number of marketed dihydropyridine calcium channel blockers have mineralocorticoid receptor antagonist activity. Hypertension. 2008 Mar;51(3):742-8. Epub 2008 Feb 4. Pubmed

12. Troponin C, skeletal muscle

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: other

Components

Name UniProt ID Details
Troponin C, skeletal muscle P02585 Details

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
  2. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

13. Troponin C, slow skeletal and cardiac muscles

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: other

Components

Name UniProt ID Details
Troponin C, slow skeletal and cardiac muscles P63316 Details

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

Enzymes

1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. AstraZeneca LP. Plendil® (felodipine) extended-release tablets prescribing information. Wilmington, DE; 2003 Nov.
  2. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  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. Epub 2009 Nov 24. Pubmed
  4. 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

2. Cytochrome P450 3A5

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A5 P20815 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.

3. Cytochrome P450 3A7

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A7 P24462 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.

4. Cytochrome P450 2C8

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C8 P10632 Details

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. Epub 2008 Apr 15. Pubmed
  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
  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. Epub 2009 Nov 24. Pubmed

5. Cytochrome P450 2C9

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C9 P11712 Details

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. Epub 2009 Nov 24. Pubmed

6. Cytochrome P450 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

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. Epub 2009 Nov 24. Pubmed

Transporters

1. Multidrug resistance protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

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

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Drug created on June 13, 2005 07:24 / Updated on January 15, 2014 09:42