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Identification
- Summary
Felodipine is a calcium channel blocker used to treat hypertension.
- Brand Names
- Plendil
- Generic Name
- Felodipine
- DrugBank Accession Number
- DB01023
- Background
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.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Felodipine (DB01023)
- Weight
- Average: 384.254
Monoisotopic: 383.069113515 - Chemical Formula
- C18H19Cl2NO4
- Synonyms
- (±)-ethyl methyl 4-(2,3-dichlorophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate
- 3-ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylate
- 4-(2,3-dichlorophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic acid ethyl methyl ester
- Felodipina
- Felodipine
- Felodipino
- Felodipinum
Pharmacology
- Indication
For the treatment of mild to moderate essential hypertension.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Hypertension •••••••••••• ••••••• •••••••• ••••••• Used in combination to manage Hypertension Regimen in combination with: Ramipril (DB00178) ••• ••••• •••••••• •••••• ••••••••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Felodipine 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 action
Felodipine 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.
Target Actions Organism AVoltage-dependent L-type calcium channel subunit alpha-1C inhibitorHumans AVoltage-dependent calcium channel subunit alpha-2/delta-1 inhibitorHumans AVoltage-dependent L-type calcium channel subunit beta-2 inhibitorHumans AVoltage-dependent L-type calcium channel subunit alpha-1D inhibitorHumans AVoltage-dependent L-type calcium channel subunit alpha-1S inhibitorHumans UVoltage-dependent T-type calcium channel subunit alpha-1H inhibitorHumans UVoltage-dependent calcium channel subunit alpha-2/delta-2 inhibitorHumans UDual specificity calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B inhibitorHumans UDual specificity calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A inhibitorHumans UMineralocorticoid receptor antagonistHumans UTroponin C, skeletal muscle otherHumans UTroponin C, slow skeletal and cardiac muscles otherHumans UCalmodulin otherHumans - Absorption
Is 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 binding
99%, primarily to the albumin fraction.
- Metabolism
Hepatic metabolism primarily via cytochrome P450 3A4. Six metabolites with no appreciable vasodilatory effects have been identified.
Hover over products below to view reaction partners
- Route of elimination
Although 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-life
17.5-31.5 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]
- Adverse Effects
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Symptoms of overdose include excessive peripheral vasodilation with marked hypotension and possibly bradycardia. Oral rat LD50 is 1050 mg/kg.
- Pathways
Pathway Category Felodipine Metabolism Pathway Drug metabolism Felodipine Action Pathway Drug action - Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbaloparatide The risk or severity of adverse effects can be increased when Felodipine is combined with Abaloparatide. Abametapir The serum concentration of Felodipine can be increased when it is combined with Abametapir. Abatacept The metabolism of Felodipine can be increased when combined with Abatacept. Abrocitinib The metabolism of Abrocitinib can be decreased when combined with Felodipine. Acalabrutinib The metabolism of Felodipine can be decreased when combined with Acalabrutinib. - Food Interactions
- Avoid grapefruit products.
- Take with or without food. The absorption is unaffected by food.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Images
- International/Other Brands
- Felodur ER / Felogard / Penedil / Plendil Depottab (AstraZeneca) / Plendil ER (AstraZeneca) / Plendil Retard (AstraZeneca) / Splendil
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Felodipine Tablet, extended release 10 mg/1 Oral Med Pharma Co., Ltd. 2011-06-07 2012-05-15 US 
Felodipine Tablet, extended release 5 mg/1 Oral Med Pharma Co., Ltd. 2011-06-07 2012-05-15 US Felodipine Tablet, extended release 2.5 mg/1 Oral Med Pharma Co., Ltd. 2011-06-07 2012-05-15 US Felodipineextended-release Tablets Tablet, extended release 10 mg/1 Oral Ranbaxy Inc. 2008-09-10 Not applicable US Felodipineextended-release Tablets Tablet, extended release 5 mg/1 Oral Ranbaxy Inc. 2008-09-10 Not applicable US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Apo-felodipine Tablet, extended release 2.5 mg Oral Apotex Corporation 2016-04-22 Not applicable Canada 
Apo-felodipine Tablet, extended release 10 mg Oral Apotex Corporation 2016-04-22 Not applicable Canada Apo-felodipine Tablet, extended release 5 mg Oral Apotex Corporation 2016-04-22 Not applicable Canada Felodipine Tablet, film coated, extended release 5 mg/1 Oral Av Kare, Inc. 2014-03-31 2016-01-13 US Felodipine Tablet, extended release 5 mg/1 Oral Yiling Pharmaceutical Inc. 2019-08-01 Not applicable US - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Altace Plus Felodipine 2.5mg + 2.5mg Felodipine (2.5 mg) + Ramipril (2.5 mg) Tablet Oral Sanofi Aventis 2006-06-27 2012-10-10 Canada Altace Plus Felodipine 5mg + 5mg Felodipine (5 mg) + Ramipril (5 mg) Tablet Oral Sanofi Aventis 2006-06-27 2012-10-15 Canada DELIX DUO 2.5 MG/2.5 MG TABLET, 30 ADET Felodipine (2.5 mg) + Ramipril (2.5 mg) Tablet Oral SANOFİ SAĞLIK ÜRÜNLERİ LTD. ŞTİ. 2015-02-03 2021-12-28 Turkey 
DELIX DUO 5 MG/5 MG FİLM KAPLI TABLET, 30 ADET Felodipine (5 mg) + Ramipril (5 mg) Tablet, coated SANOFİ SAĞLIK ÜRÜNLERİ LTD. ŞTİ. 2015-02-03 2021-12-28 Turkey DELMUNO 2.5/2.5MG Felodipine (2.5 mg) + Ramipril (2.5 mg) Tablet, extended release Oral 2016-07-01 Not applicable Germany 
Categories
- ATC Codes
- C07FB02 — Metoprolol and felodipine
- C07FB — Beta blocking agents and calcium channel blockers
- C07F — BETA BLOCKING AGENTS, OTHER COMBINATIONS
- C07 — BETA BLOCKING AGENTS
- C — CARDIOVASCULAR SYSTEM
- C08CA — Dihydropyridine derivatives
- C08C — SELECTIVE CALCIUM CHANNEL BLOCKERS WITH MAINLY VASCULAR EFFECTS
- C08 — CALCIUM CHANNEL BLOCKERS
- C — CARDIOVASCULAR SYSTEM
- Drug Categories
- ACE Inhibitors and Calcium Channel Blockers
- Agents causing hyperkalemia
- Antiarrhythmic agents
- Antihypertensive Agents
- Antihypertensive Agents Indicated for Hypertension
- Beta blocking agents and calcium channel blockers
- Bradycardia-Causing Agents
- BSEP/ABCB11 Substrates
- Calcium Channel Blockers
- Calcium Channel Blockers (Dihydropyridine)
- Calcium-Regulating Hormones and Agents
- Cardiovascular Agents
- Cytochrome P-450 CYP2C8 Inhibitors
- Cytochrome P-450 CYP2C8 Inhibitors (strong)
- Cytochrome P-450 CYP2C9 Inhibitors
- Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A5 Substrates
- Cytochrome P-450 CYP3A7 Substrates
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Dihydropyridine Derivatives
- Dihydropyridines
- Hypotensive Agents
- Membrane Transport Modulators
- P-glycoprotein inhibitors
- Potential QTc-Prolonging Agents
- Pyridines
- QTc Prolonging Agents
- Selective Calcium Channel Blockers With Mainly Vascular Effects
- Vasodilating Agents
- Chemical TaxonomyProvided by Classyfire
- Description
- This 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.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Pyridines and derivatives
- Sub Class
- Hydropyridines
- Direct Parent
- Dihydropyridinecarboxylic acids and derivatives
- Alternative Parents
- Dichlorobenzenes / Dicarboxylic acids and derivatives / Aryl chlorides / Vinylogous amides / Methyl esters / Enoate esters / Amino acids and derivatives / Enamines / Dialkylamines / Azacyclic compounds show 5 more
- Substituents
- 1,2-dichlorobenzene / Alpha,beta-unsaturated carboxylic ester / Amine / Amino acid or derivatives / Aromatic heteromonocyclic compound / Aryl chloride / Aryl halide / Azacycle / Benzenoid / Carbonyl group show 22 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- ethyl ester, dichlorobenzene, methyl ester, dihydropyridine (CHEBI:585948)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- OL961R6O2C
- CAS number
- 72509-76-3
- InChI Key
- RZTAMFZIAATZDJ-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
References
- Synthesis Reference
Vinay Sharma, "Preparation of micron-size felodipine particles by microfluidization." U.S. Patent US20020086061, issued July 04, 2002.
US20020086061- General References
- Dunselman PH, Edgar B: Felodipine clinical pharmacokinetics. Clin Pharmacokinet. 1991 Dec;21(6):418-30. [Article]
- External Links
- Human Metabolome Database
- HMDB0015158
- KEGG Drug
- D00319
- PubChem Compound
- 3333
- PubChem Substance
- 46506968
- ChemSpider
- 3216
- BindingDB
- 189379
- 4316
- ChEBI
- 585948
- ChEMBL
- CHEMBL1480
- Therapeutic Targets Database
- DAP000487
- PharmGKB
- PA449591
- Guide to Pharmacology
- GtP Drug Page
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- PDRhealth
- PDRhealth Drug Page
- Wikipedia
- Felodipine
- FDA label
- Download (228 KB)
- MSDS
- Download (55.4 KB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Completed Not Available Coronavirus Disease 2019 (COVID‑19) / COVID / Hypertension 1 somestatus stop reason just information to hide Not Available Completed Not Available Healthy Volunteers (HV) 2 somestatus stop reason just information to hide Not Available Completed Not Available Hypertension 1 somestatus stop reason just information to hide Not Available Completed Treatment Hypertension 2 somestatus stop reason just information to hide Not Available Unknown Status Basic Science Hypertension / Microcirculation / Resistance, Insulin 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- A-S Medication Solutions LLC
- AstraZeneca Inc.
- Atlantic Biologicals Corporation
- Bryant Ranch Prepack
- Cardinal Health
- Heartland Repack Services LLC
- Lake Erie Medical and Surgical Supply
- Liberty Pharmaceuticals
- Merck & Co.
- Murfreesboro Pharmaceutical Nursing Supply
- Mutual Pharmaceutical Co.
- Mylan
- Nucare Pharmaceuticals Inc.
- PD-Rx Pharmaceuticals Inc.
- Physicians Total Care Inc.
- Preferred Pharmaceuticals Inc.
- Prepackage Specialists
- Prepak Systems Inc.
- Prescript Pharmaceuticals
- Ranbaxy Laboratories
- Resource Optimization and Innovation LLC
- Richmond Pharmacy
- Sandhills Packaging Inc.
- UDL Laboratories
- Va Cmop Dallas
- Vangard Labs Inc.
- Dosage Forms
Form Route Strength Tablet Oral Tablet, coated Tablet Oral 5.0000 mg Tablet, delayed release Oral 10 mg Tablet, delayed release Oral 5 mg Tablet Oral 5 MG Tablet, extended release Oral Tablet, film coated Oral 10 mg Tablet, film coated Oral 10 mg/1 Tablet, film coated Oral 2.5 mg/1 Tablet, film coated Oral 5 mg/1 Tablet, film coated, extended release Oral 10 mg/1 Tablet, film coated, extended release Oral 2.5 mg/1 Tablet, film coated, extended release Oral 5 mg/1 Tablet, extended release Oral 10 mg/1 Tablet, extended release Oral 2.5 mg/1 Tablet, extended release Oral 5 mg/1 Tablet Oral 5.000 mg Tablet Oral 5.00 mg Tablet, extended release Oral Tablet Oral 10 MG Tablet, extended release Oral 10 mg / tab Tablet, extended release Oral 2.5 mg / srt Tablet, extended release Oral 5 mg / tab Tablet, film coated Oral Tablet, extended release Oral 10 mg Tablet, extended release Oral 5 mg Tablet, extended release Oral 2.5 mg Tablet, film coated Oral 2.5 mg Tablet, film coated Oral 5 mg - Prices
Unit description Cost Unit Plendil 10 mg 24 Hour tablet 3.17USD tablet Plendil er 10 mg tablet 3.05USD tablet Plendil 10 mg tablet sa 2.96USD tablet Felodipine 10 mg 24 Hour tablet 2.95USD tablet Plendil er 2.5 mg tablet 2.94USD tablet Felodipine er 10 mg tablet 2.72USD tablet Plendil er 5 mg tablet 2.6USD tablet Plendil 5 mg 24 Hour tablet 1.77USD tablet Plendil 2.5 mg 24 Hour tablet 1.76USD tablet Felodipine 5 mg 24 Hour tablet 1.67USD tablet Plendil 2.5 mg tablet sa 1.65USD tablet Plendil 5 mg tablet sa 1.65USD tablet Felodipine 2.5 mg 24 Hour tablet 1.57USD tablet Felodipine er 2.5 mg tablet 1.51USD tablet Felodipine er 5 mg tablet 1.51USD tablet Renedil 10 mg Extended-Release Tablet 1.22USD tablet Plendil 10 mg Extended-Release Tablet 1.15USD tablet Renedil 5 mg Extended-Release Tablet 0.81USD tablet Plendil 5 mg Extended-Release Tablet 0.77USD tablet Sandoz Felodipine 10 mg Extended-Release Tablet 0.73USD tablet Renedil 2.5 mg Extended-Release Tablet 0.6USD tablet Plendil 2.5 mg Extended-Release Tablet 0.57USD tablet Sandoz Felodipine 5 mg Extended-Release Tablet 0.48USD tablet DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 145 °C Not Available water solubility 19.7 mg/L Not Available logP 3.86 SANGSTER (1994) Caco2 permeability -4.64 ADME Research, USCD - Predicted Properties
Property Value Source Water Solubility 0.00715 mg/mL ALOGPS logP 4.36 ALOGPS logP 3.44 Chemaxon logS -4.7 ALOGPS pKa (Strongest Acidic) 19.46 Chemaxon pKa (Strongest Basic) -6.6 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 64.63 Å2 Chemaxon Rotatable Bond Count 6 Chemaxon Refractivity 99.2 m3·mol-1 Chemaxon Polarizability 37.96 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - 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 inhibitor Inhibitor 0.8948 CYP450 2D6 inhibitor Non-inhibitor 0.9232 CYP450 2C19 inhibitor Inhibitor 0.8994 CYP450 3A4 inhibitor 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
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 190.0924001 predictedDarkChem Lite v0.1.0 [M-H]- 196.47217 predictedDeepCCS 1.0 (2019) [M+H]+ 190.3810001 predictedDarkChem Lite v0.1.0 [M+H]+ 199.05714 predictedDeepCCS 1.0 (2019) [M+Na]+ 190.2508001 predictedDarkChem Lite v0.1.0 [M+Na]+ 207.75827 predictedDeepCCS 1.0 (2019)
Targets
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Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Pore-forming, alpha-1C subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents (PubMed:11741969, PubMed:12176756, PubMed:12181424, PubMed:15454078, PubMed:15863612, PubMed:16299511, PubMed:17071743, PubMed:17224476, PubMed:20953164, PubMed:23677916, PubMed:24728418, PubMed:26253506, PubMed:27218670, PubMed:29078335, PubMed:29742403, PubMed:30023270, PubMed:30172029, PubMed:34163037, PubMed:7737988, PubMed:8099908, PubMed:8392192, PubMed:9013606, PubMed:9087614, PubMed:9607315). Mediates influx of calcium ions into the cytoplasm, and thereby triggers calcium release from the sarcoplasm (By similarity). Plays an important role in excitation-contraction coupling in the heart. Required for normal heart development and normal regulation of heart rhythm (PubMed:15454078, PubMed:15863612, PubMed:17224476, PubMed:24728418, PubMed:26253506). Required for normal contraction of smooth muscle cells in blood vessels and in the intestine. Essential for normal blood pressure regulation via its role in the contraction of arterial smooth muscle cells (PubMed:28119464). Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group (Probable)
- Specific Function
- Alpha-actinin binding
- Gene Name
- CACNA1C
- Uniprot ID
- Q13936
- Uniprot Name
- Voltage-dependent L-type calcium channel subunit alpha-1C
- Molecular Weight
- 248974.1 Da
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- 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. [Article]
- 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. [Article]
- Striessnig, J. (2004). Ca 2+ channel blockers. In Encyclopedic reference of molecular pharmacology (pp. 201-207). Berlin: Springer. [ISBN:9783540298328]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel (PubMed:35293990). Plays an important role in excitation-contraction coupling (By similarity)
- Specific Function
- Metal ion binding
- Gene Name
- CACNA2D1
- Uniprot ID
- P54289
- Uniprot Name
- Voltage-dependent calcium channel subunit alpha-2/delta-1
- Molecular Weight
- 124566.93 Da
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- 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. [Article]
- 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. [Article]
- Striessnig, J. (2004). Ca 2+ channel blockers. In Encyclopedic reference of molecular pharmacology (pp. 201-207). Berlin: Springer. [ISBN:9783540298328]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Beta subunit of voltage-dependent calcium channels which contributes to the function of the calcium channel by increasing peak calcium current (By similarity). Plays a role in shifting voltage dependencies of activation and inactivation of the channel (By similarity). May modulate G protein inhibition (By similarity). May contribute to beta-adrenergic augmentation of Ca(2+) influx in cardiomyocytes, thereby regulating increases in heart rate and contractile force (PubMed:36424916). Involved in membrane targeting of the alpha-1 subunit CACNA1C (PubMed:17525370)
- Specific Function
- Actin filament binding
- Gene Name
- CACNB2
- Uniprot ID
- Q08289
- Uniprot Name
- Voltage-dependent L-type calcium channel subunit beta-2
- Molecular Weight
- 73579.925 Da
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- 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. [Article]
- 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. [Article]
- Striessnig, J. (2004). Ca 2+ channel blockers. In Encyclopedic reference of molecular pharmacology (pp. 201-207). Berlin: Springer. [ISBN:9783540298328]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General 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, and by benzothiazepines
- Specific Function
- Alpha-actinin binding
- Gene Name
- CACNA1D
- Uniprot ID
- Q01668
- Uniprot Name
- Voltage-dependent L-type calcium channel subunit alpha-1D
- Molecular Weight
- 245138.75 Da
References
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Pore-forming, alpha-1S subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents in skeletal muscle. Calcium channels containing the alpha-1S subunit play an important role in excitation-contraction coupling in skeletal muscle via their interaction with RYR1, which triggers Ca(2+) release from the sarcoplasmic reticulum and ultimately results in muscle contraction. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group
- Specific Function
- Calmodulin binding
- Gene Name
- CACNA1S
- Uniprot ID
- Q13698
- Uniprot Name
- Voltage-dependent L-type calcium channel subunit alpha-1S
- Molecular Weight
- 212348.1 Da
References
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Voltage-sensitive calcium channel that gives rise to T-type calcium currents. T-type calcium channels belong to the 'low-voltage activated (LVA)' group. A particularity of this type of channel is an opening at quite negative potentials, and a voltage-dependent inactivation (PubMed:27149520, PubMed:9670923, PubMed:9930755). T-type channels serve pacemaking functions in both central neurons and cardiac nodal cells and support calcium signaling in secretory cells and vascular smooth muscle (Probable). They may also be involved in the modulation of firing patterns of neurons (PubMed:15048902). In the adrenal zona glomerulosa, participates in the signaling pathway leading to aldosterone production in response to either AGT/angiotensin II, or hyperkalemia (PubMed:25907736, PubMed:27729216)
- Specific Function
- High voltage-gated calcium channel activity
- Gene Name
- CACNA1H
- Uniprot ID
- O95180
- Uniprot Name
- Voltage-dependent T-type calcium channel subunit alpha-1H
- Molecular Weight
- 259160.2 Da
References
- 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. [Article]
- 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. doi: 10.1124/jpet.108.145672. Epub 2008 Oct 30. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Acts as a regulatory subunit for P/Q-type calcium channel (CACNA1A), N-type (CACNA1B), L-type (CACNA1C OR CACNA1D) and possibly T-type (CACNA1G) (PubMed:15111129, PubMed:23339110). Overexpression induces apoptosis
- Specific Function
- Metal ion binding
- Gene Name
- CACNA2D2
- Uniprot ID
- Q9NY47
- Uniprot Name
- Voltage-dependent calcium channel subunit alpha-2/delta-2
- Molecular Weight
- 129816.095 Da
References
- 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. [Article]
- 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. doi: 10.1124/jpet.108.145672. Epub 2008 Oct 30. [Article]
Details8. Dual specificity calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Cyclic nucleotide phosphodiesterase with a dual specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes (PubMed:15260978, PubMed:8855339, PubMed:9419816). Has a preference for cGMP as a substrate (PubMed:9419816)
- Specific Function
- 3',5'-cyclic-amp phosphodiesterase activity
- Gene Name
- PDE1B
- Uniprot ID
- Q01064
- Uniprot Name
- Dual specificity calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B
- Molecular Weight
- 61379.235 Da
References
- 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. [Article]
- 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. [Article]
Details9. Dual specificity calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Calcium/calmodulin-dependent cyclic nucleotide phosphodiesterase with a dual specificity for the second messengers cGMP and cAMP, which are key regulators of many important physiological processes. Has a higher efficiency with cGMP compared to cAMP
- Specific Function
- Calmodulin binding
- Gene Name
- PDE1A
- Uniprot ID
- P54750
- Uniprot Name
- Dual specificity calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A
- Molecular Weight
- 61251.38 Da
References
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol. Binds to mineralocorticoid response elements (MRE) and transactivates target genes. The effect of MC is to increase ion and water transport and thus raise extracellular fluid volume and blood pressure and lower potassium levels
- Specific Function
- Dna-binding transcription factor activity
- Gene Name
- NR3C2
- Uniprot ID
- P08235
- Uniprot Name
- Mineralocorticoid receptor
- Molecular Weight
- 107080.615 Da
References
- 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. doi: 10.1161/HYPERTENSIONAHA.107.103580. Epub 2008 Feb 4. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Other
- General Function
- Troponin is the central regulatory protein of striated muscle contraction. Tn consists of three components: Tn-I which is the inhibitor of actomyosin ATPase, Tn-T which contains the binding site for tropomyosin and Tn-C. The binding of calcium to Tn-C abolishes the inhibitory action of Tn on actin filaments
- Specific Function
- Calcium ion binding
- Gene Name
- TNNC2
- Uniprot ID
- P02585
- Uniprot Name
- Troponin C, skeletal muscle
- Molecular Weight
- 18121.895 Da
References
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Other
- General Function
- Troponin is the central regulatory protein of striated muscle contraction. Tn consists of three components: Tn-I which is the inhibitor of actomyosin ATPase, Tn-T which contains the binding site for tropomyosin and Tn-C. The binding of calcium to Tn-C abolishes the inhibitory action of Tn on actin filaments
- Specific Function
- Actin filament binding
- Gene Name
- TNNC1
- Uniprot ID
- P63316
- Uniprot Name
- Troponin C, slow skeletal and cardiac muscles
- Molecular Weight
- 18402.36 Da
References
- 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. [Article]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Other
- General Function
- Calmodulin acts as part of a calcium signal transduction pathway by mediating the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding (PubMed:16760425, PubMed:23893133, PubMed:26969752, PubMed:27165696, PubMed:28890335, PubMed:31454269, PubMed:35568036). Calcium-binding is required for the activation of calmodulin (PubMed:16760425, PubMed:23893133, PubMed:26969752, PubMed:27165696, PubMed:28890335, PubMed:31454269, PubMed:35568036). Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases, such as myosin light-chain kinases and calmodulin-dependent protein kinase type II (CaMK2), and phosphatases (PubMed:16760425, PubMed:23893133, PubMed:26969752, PubMed:27165696, PubMed:28890335, PubMed:31454269, PubMed:35568036). Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis (PubMed:16760425). Is a regulator of voltage-dependent L-type calcium channels (PubMed:31454269). Mediates calcium-dependent inactivation of CACNA1C (PubMed:26969752). Positively regulates calcium-activated potassium channel activity of KCNN2 (PubMed:27165696). Forms a potassium channel complex with KCNQ1 and regulates electrophysiological activity of the channel via calcium-binding (PubMed:25441029). Acts as a sensor to modulate the endoplasmic reticulum contacts with other organelles mediated by VMP1:ATP2A2 (PubMed:28890335)
- Specific Function
- Adenylate cyclase activator activity
Components:
| Name | UniProt ID |
|---|---|
| Calmodulin-1 | P0DP23 |
| Calmodulin-2 | P0DP24 |
| Calmodulin-3 | P0DP25 |
References
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Mills JS, Bailey BL, Johnson JD: Cooperativity among calmodulin's drug binding sites. Biochemistry. 1985 Aug 27;24(18):4897-902. [Article]
- 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. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- 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. [Article]
- Lown KS, Bailey DG, Fontana RJ, Janardan SK, Adair CH, Fortlage LA, Brown MB, Guo W, Watkins PB: Grapefruit juice increases felodipine oral availability in humans by decreasing intestinal CYP3A protein expression. J Clin Invest. 1997 May 15;99(10):2545-53. doi: 10.1172/JCI119439. [Article]
- Mitsui T, Nemoto T, Miyake T, Nagao S, Ogawa K, Kato M, Ishigai M, Yamada H: A useful model capable of predicting the clearance of cytochrome 3A4 (CYP3A4) substrates in humans: validity of CYP3A4 transgenic mice lacking their own Cyp3a enzymes. Drug Metab Dispos. 2014 Sep;42(9):1540-7. doi: 10.1124/dmd.114.057935. Epub 2014 Jul 8. [Article]
- Flockhart Table of Drug Interactions [Link]
- Felodipine - LiverTox - NIH [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of steroid hormones and vitamins (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Exhibits high catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes 6beta-hydroxylation of the steroid hormones testosterone, progesterone, and androstenedione (PubMed:2732228). Catalyzes the oxidative conversion of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes all trans-retinoic acid (atRA) to 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Also involved in the oxidative metabolism of xenobiotics, including calcium channel blocking drug nifedipine and immunosuppressive drug cyclosporine (PubMed:2732228)
- Specific Function
- Aromatase activity
- Gene Name
- CYP3A5
- Uniprot ID
- P20815
- Uniprot Name
- Cytochrome P450 3A5
- Molecular Weight
- 57108.065 Da
References
- Flockhart Table of Drug Interactions [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of steroid hormones and vitamins during embryogenesis (PubMed:11093772, PubMed:12865317, PubMed:14559847, PubMed:17178770, PubMed:9555064). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:11093772, PubMed:12865317, PubMed:14559847, PubMed:17178770, PubMed:9555064). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes 3beta-hydroxyandrost-5-en-17-one (dehydroepiandrosterone, DHEA), a precursor in the biosynthesis of androgen and estrogen steroid hormones (PubMed:17178770, PubMed:9555064). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1), particularly D-ring hydroxylated estrone at the C16-alpha position (PubMed:12865317, PubMed:14559847). Mainly hydroxylates all trans-retinoic acid (atRA) to 4-hydroxyretinoate and may play a role in atRA clearance during fetal development (PubMed:11093772). Also involved in the oxidative metabolism of xenobiotics including anticonvulsants (PubMed:9555064)
- Specific Function
- All-trans retinoic acid 18-hydroxylase activity
- Gene Name
- CYP3A7
- Uniprot ID
- P24462
- Uniprot Name
- Cytochrome P450 3A7
- Molecular Weight
- 57469.95 Da
References
- Flockhart Table of Drug Interactions [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Primarily catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) with a preference for the last double bond (PubMed:15766564, PubMed:19965576, PubMed:7574697). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes all trans-retinoic acid toward its 4-hydroxylated form (PubMed:11093772). Displays 16-alpha hydroxylase activity toward estrogen steroid hormones, 17beta-estradiol (E2) and estrone (E1) (PubMed:14559847). Plays a role in the oxidative metabolism of xenobiotics. It is the principal enzyme responsible for the metabolism of the anti-cancer drug paclitaxel (taxol) (PubMed:26427316)
- Specific Function
- Arachidonic acid epoxygenase activity
- Gene Name
- CYP2C8
- Uniprot ID
- P10632
- Uniprot Name
- Cytochrome P450 2C8
- Molecular Weight
- 55824.275 Da
References
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Enzyme inhibition data obtained from an in vitro study using felodipine at supratherapeutic concentrations.
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids and steroids (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:15766564, PubMed:19965576, PubMed:7574697, PubMed:9866708). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Exhibits low catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes bisallylic hydroxylation and hydroxylation with double-bond migration of polyunsaturated fatty acids (PUFA) (PubMed:9435160, PubMed:9866708). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan (PubMed:25994031)
- Specific Function
- (r)-limonene 6-monooxygenase activity
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- Ma B, Prueksaritanont T, Lin JH: Drug interactions with calcium channel blockers: possible involvement of metabolite-intermediate complexation with CYP3A. Drug Metab Dispos. 2000 Feb;28(2):125-30. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of fatty acids, steroids and retinoids (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:19965576, PubMed:20972997). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:18698000, PubMed:21289075). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Catalyzes the oxidative transformations of all-trans retinol to all-trans retinal, a precursor for the active form all-trans-retinoic acid (PubMed:10681376). Also involved in the oxidative metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants
- Specific Function
- Anandamide 11,12 epoxidase activity
- Gene Name
- CYP2D6
- Uniprot ID
- P10635
- Uniprot Name
- Cytochrome P450 2D6
- Molecular Weight
- 55768.94 Da
References
- Ma B, Prueksaritanont T, Lin JH: Drug interactions with calcium channel blockers: possible involvement of metabolite-intermediate complexation with CYP3A. Drug Metab Dispos. 2000 Feb;28(2):125-30. [Article]
- Snyder BD, Rowland A, Polasek TM, Miners JO, Doogue MP: Evaluation of felodipine as a potential perpetrator of pharmacokinetic drug-drug interactions. Eur J Clin Pharmacol. 2014 Sep;70(9):1115-22. doi: 10.1007/s00228-014-1716-8. Epub 2014 Jul 17. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218)
- Specific Function
- Abc-type xenobiotic transporter activity
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- ATP-dependent translocase ABCB1
- Molecular Weight
- 141477.255 Da
References
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Catalyzes the transport of the major hydrophobic bile salts, such as taurine and glycine-conjugated cholic acid across the canalicular membrane of hepatocytes in an ATP-dependent manner, therefore participates in hepatic bile acid homeostasis and consequently to lipid homeostasis through regulation of biliary lipid secretion in a bile salts dependent manner (PubMed:15791618, PubMed:16332456, PubMed:18985798, PubMed:19228692, PubMed:20010382, PubMed:20398791, PubMed:22262466, PubMed:24711118, PubMed:29507376, PubMed:32203132). Transports taurine-conjugated bile salts more rapidly than glycine-conjugated bile salts (PubMed:16332456). Also transports non-bile acid compounds, such as pravastatin and fexofenadine in an ATP-dependent manner and may be involved in their biliary excretion (PubMed:15901796, PubMed:18245269)
- Specific Function
- Abc-type bile acid transporter activity
- Gene Name
- ABCB11
- Uniprot ID
- O95342
- Uniprot Name
- Bile salt export pump
- Molecular Weight
- 146405.83 Da
References
- Pedersen JM, Matsson P, Bergstrom CA, Hoogstraate J, Noren A, LeCluyse EL, Artursson P: Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43. doi: 10.1093/toxsci/kft197. Epub 2013 Sep 6. [Article]
Drug created at June 13, 2005 13:24 / Updated at September 16, 2024 01:06