Carvedilol

Identification

Summary

Carvedilol is a non selective beta-adrenergic antagonist used to treat mild to severe chronic heart failure, hypertension, and left ventricular dysfunction following myocardial infarction in clinically stable patients.

Brand Names
Coreg
Generic Name
Carvedilol
DrugBank Accession Number
DB01136
Background

Carvedilol is a racemic mixture where the S(-) enantiomer is both a beta and alpha-1 adrenoceptor blocker, and the R(+) enantiomer is an alpha-1 adrenoceptor blocker.5,6 It is currently used to treat heart failure, left ventricular dysfunction, and hypertension.5,6 The dual action of carvedilol is advantageous in combination therapies as moderate doses of 2 drugs have a decreased incidence of adverse effects compared to high dose monotherapy in the treatment of moderate hypertension.4

Carvedilol was granted FDA approval on 14 September 1995.5

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 406.4742
Monoisotopic: 406.18925733
Chemical Formula
C24H26N2O4
Synonyms
  • (+-)-1-(Carbazol-4-yloxy)-3-((2-(o-methoxyphenoxy)ethyl)amino)-2-propanol
  • Carvedilol
  • Carvédilol
  • Carvedilolum
External IDs
  • SKF 105517

Pharmacology

Indication

Carvedilol is indicated to treat mild to severe heart failure, left ventricular dysfunction after myocardial infarction with ventricular ejection fraction ≤40%, or hypertension.5,6

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Management ofAtrial fibrillation••• •••••
Management ofChronic stable angina pectoris••• •••••
Management ofHypertension••••••••••••
Management ofLvef ≤40% left ventricular dysfunction••••••••••••
Management ofMild heart failure••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Carvedilol reduces tachycardia through beta adrenergic antagonism and lowers blood pressure through alpha-1 adrenergic antagonism.5,6 It has a long duration of action as it is generally taken once daily and has a broad therapeutic index as patients generally take 10-80mg daily.5,6 Patients taking carvedilol should not abruptly stop taking this medication as this may exacerbate coronary artery disease.5,6

Mechanism of action

Carvedilol inhibits exercise induce tachycardia through its inhibition of beta adrenoceptors.4 Carvedilol's action on alpha-1 adrenergic receptors relaxes smooth muscle in vasculature, leading to reduced peripheral vascular resistance and an overall reduction in blood pressure.1,4 At higher doses, calcium channel blocking and antioxidant activity can also be seen.1 The antioxidant activity of carvedilol prevents oxidation of low density lipoprotein and its uptake into coronary circulation.1

TargetActionsOrganism
ABeta-1 adrenergic receptor
antagonist
Humans
AAlpha-1A adrenergic receptor
antagonist
potentiator
Humans
AAlpha-1 adrenergic receptors
inhibitor
Humans
UNADH dehydrogenase [ubiquinone] 1 subunit C2
inhibitor
Humans
UBeta-2 adrenergic receptor
antagonist
Humans
UVascular endothelial growth factor A
other
Humans
UNatriuretic peptides B
other
Humans
UGap junction alpha-1 protein
other
Humans
UPotassium voltage-gated channel subfamily H member 2
inhibitor
Humans
UVascular cell adhesion protein 1
inhibitor
Humans
UAlpha-1D adrenergic receptor
antagonist
Humans
UAlpha-1B adrenergic receptor
antagonist
Humans
UAlpha-2C adrenergic receptor
antagonist
Humans
UAlpha-2B adrenergic receptor
antagonist
Humans
UAlpha-2A adrenergic receptor
antagonist
Humans
UE-selectin
inhibitor
Humans
UHypoxia-inducible factor 1-alpha
modulator
Humans
UInward rectifier potassium channel 4
inhibitor
Humans
UInward rectifier potassium channel 2
inhibitor
Humans
Absorption

Carvedilol has a bioavailability of 25-35%.4,5,6 Carvedilol has a Tmax of 1 to 2 hours.4 Taking carvedilol with a meal increases Tmax without increasing AUC.4 Carvedilol doses of 50mg lead to a Cmax of 122-262µg/L and an AUC of 717-1600µg/L*h.4 Carvedilol doses of 25mg lead to a Cmax of 24-151µg/L and an AUC of 272-947µg/L*h.4 Carvedilol doses of 12.5mg lead to a Cmax of 58-69µg/L and an AUC of 208-225µg/L*h.4

Volume of distribution

Carvedilol has a volume of distribution of 1.5-2L/kg4 or 115L.6

Protein binding

Carvedilol is 98% protein bound in plasma.5,6 95% of carvedilol is bound to serum albumin.4

Metabolism

Carvedilol can be hydroxlated at the 1 position by CYP2D6, CYP1A2, or CYP1A1 to form 1-hydroxypheylcarvedilol; at the 4 position by CYP2D6, CYP2E1, CYP2C9, or CYP3A4 to form 4'-hydroxyphenylcarvedilol; at the 5 position by CYP2D6, CYP2C9, or CYP3A4 to form 5'-hydroxyphenylcarvedilol; and at the 8 position by CYP1A2, CYP3A4, and CYP1A1 to form 8-hydroxycarbazolylcarvedilol.2 Carvedilol can also be demethylated by CYP2C9, CYP2D6, CYP1A2, or CYP2E1 to form O-desmethylcarvedilol.2 Carvedilol and its metabolites may undergo further sulfate conjugation or glucuronidation before elimination.2 Carvedilol can be O-glucuronidated by UGT1A1, UGT2B4, and UGT2B7 to form carvedilol glucuronide.3

Hover over products below to view reaction partners

Route of elimination

16% of carvedilol is excreted in the urine with <2% excreted as unmetabolized drug.4 Carvedilol is primarily excreted in the bile and feces.5,6

Half-life

The half life of carvedilol is between 7-10 hours, though significantly shorter half lives have also been reported.4,5,6

Clearance

The plasma clearance of carvedilol has been reported as 0.52L/kg4 or 500-700mL/min.5,6

Adverse Effects
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Toxicity

Patients experiencing an overdose may present with hypotension, bradycardia, cardiac insufficiency, cardiogenic shock, and cardiac arrest.5,6 Patients should remain in a supine position and may be given atropine for bradycardia and glucagon followed by sympathomimetics to support cardiovascular function.5,6

Pathways
PathwayCategory
Carvedilol Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Beta-1 adrenergic receptor---(C;C) / (C;G) / (A;A)C Allele, homozygousEffect Directly StudiedPatients with this genotype in ADRB1 have an increased likelihood of responding to carvedilol for the treatment of increased blood pressure.Details
Cytochrome P450 2D6CYP2D6*3Not AvailableC alleleEffect InferredPoor drug metabolizer, increased dizziness.Details
Cytochrome P450 2D6CYP2D6*4Not AvailableC alleleEffect InferredPoor drug metabolizer, increased dizziness.Details
Cytochrome P450 2D6CYP2D6*5Not AvailableWhole-gene deletionEffect InferredPoor drug metabolizer, increased dizziness.Details
Cytochrome P450 2D6CYP2D6*6Not Available1707delTEffect InferredPoor drug metabolizer, increased dizziness.Details
Cytochrome P450 2D6CYP2D6*7Not Available2935A>CEffect InferredPoor drug metabolizer, increased dizziness.Details
Cytochrome P450 2D6CYP2D6*8Not Available1758G>TEffect InferredPoor drug metabolizer, increased dizziness.Details
Cytochrome P450 2D6CYP2D6*11Not Available883G>CEffect InferredPoor drug metabolizer, increased dizziness.Details
Cytochrome P450 2D6CYP2D6*12Not Available124G>AEffect InferredPoor drug metabolizer, increased dizziness.Details
Cytochrome P450 2D6CYP2D6*13Not AvailableCYP2D7/2D6 hybrid gene structureEffect InferredPoor drug metabolizer, increased dizziness.Details
Cytochrome P450 2D6CYP2D6*14ANot Available1758G>AEffect InferredPoor drug metabolizer, increased dizziness.Details
Cytochrome P450 2D6CYP2D6*15Not Available137insT, 137_138insTEffect InferredPoor drug metabolizer, increased dizziness.Details
Cytochrome P450 2D6CYP2D6*19Not Available2539_2542delAACTEffect InferredPoor drug metabolizer, increased dizziness.Details
Cytochrome P450 2D6CYP2D6*20Not Available1973_1974insGEffect InferredPoor drug metabolizer, increased dizziness.Details
Cytochrome P450 2D6CYP2D6*21Not Available2573insCEffect InferredPoor drug metabolizer, increased dizziness.Details
Cytochrome P450 2D6CYP2D6*31Not Available-1770G>A / -1584C>G  … show all Effect InferredPoor drug metabolizer, increased dizziness.Details
Cytochrome P450 2D6CYP2D6*36Not Available100C>T / -1426C>T  … show all Effect InferredPoor drug metabolizer, increased dizziness.Details
Cytochrome P450 2D6CYP2D6*38Not Available2587_2590delGACTEffect InferredPoor drug metabolizer, increased dizziness.Details
Cytochrome P450 2D6CYP2D6*40Not Available1863_1864ins(TTT CGC CCC)2Effect InferredPoor drug metabolizer, increased dizziness.Details
Cytochrome P450 2D6CYP2D6*42Not Available3259_3260insGTEffect InferredPoor drug metabolizer, increased dizziness.Details
Cytochrome P450 2D6CYP2D6*44Not Available2950G>CEffect InferredPoor drug metabolizer, increased dizziness.Details
Cytochrome P450 2D6CYP2D6*47Not Available100C>T / -1426C>T  … show all Effect InferredPoor drug metabolizer, increased dizziness.Details
Cytochrome P450 2D6CYP2D6*51Not Available-1584C>G / -1235A>G  … show all Effect InferredPoor drug metabolizer, increased dizziness.Details
Cytochrome P450 2D6CYP2D6*56Not Available3201C>TEffect InferredPoor drug metabolizer, increased dizziness.Details
Cytochrome P450 2D6CYP2D6*57Not Available100C>T / 310G>T  … show all Effect InferredPoor drug metabolizer, increased dizziness.Details
Cytochrome P450 2D6CYP2D6*62Not Available4044C>TEffect InferredPoor drug metabolizer, increased dizziness.Details
Cytochrome P450 2D6CYP2D6*68ANot Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer, increased dizziness.Details
Cytochrome P450 2D6CYP2D6*68BNot AvailableSimilar but not identical switch region compared to CYP2D6*68A. Found in tandem arrangement with CYP2D6*4.Effect InferredPoor drug metabolizer, increased dizziness.Details
Cytochrome P450 2D6CYP2D6*69Not Available2988G>A / -1426C>T  … show all Effect InferredPoor drug metabolizer, increased dizziness.Details
Cytochrome P450 2D6CYP2D6*92Not Available1995delCEffect InferredPoor drug metabolizer, increased dizziness.Details
Cytochrome P450 2D6CYP2D6*100Not Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer, increased dizziness.Details
Cytochrome P450 2D6CYP2D6*101Not Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer, increased dizziness.Details

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.
DrugInteraction
AbaloparatideThe risk or severity of adverse effects can be increased when Carvedilol is combined with Abaloparatide.
AbametapirThe serum concentration of Carvedilol can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Carvedilol can be increased when combined with Abatacept.
AbemaciclibThe serum concentration of Abemaciclib can be increased when it is combined with Carvedilol.
AbirateroneThe serum concentration of Carvedilol can be increased when it is combined with Abiraterone.
Food Interactions
  • Take with food. Food slows the absorption and reduces the incidence of adverse effects.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Carvedilol phosphateEQT531S367610309-89-2LHNYXTULDSJZRB-UHFFFAOYSA-N
Product Images
International/Other Brands
COREGCR
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
CarvedilolTablet6.25 mgOralPro Doc Limitee2009-06-12Not applicableCanada flag
CarvedilolTablet12.5 mgOralSivem Pharmaceuticals Ulc2004-04-06Not applicableCanada flag
CarvedilolTablet12.5 mgOralSanis Health Inc2011-06-10Not applicableCanada flag
CarvedilolTablet6.25 mgOralMeliapharm Inc2010-05-172014-06-25Canada flag
CarvedilolTablet25.0 mgOralPro Doc Limitee2009-06-12Not applicableCanada flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Apo-carvedilolTablet12.5 mgOralApotex Corporation2003-08-06Not applicableCanada flag
Apo-carvedilolTablet6.25 mgOralApotex Corporation2003-08-06Not applicableCanada flag
Apo-carvedilolTablet25 mgOralApotex Corporation2003-08-06Not applicableCanada flag
Apo-carvedilolTablet3.125 mgOralApotex Corporation2003-08-06Not applicableCanada flag
Auro-carvedilolTablet6.25 mgOralAuro Pharma Inc2014-02-06Not applicableCanada flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Co-Dilatrend 25 mg/12,5 mg - FilmtablettenCarvedilol (25 mg) + Hydrochlorothiazide (12.5 mg)Tablet, film coatedOralCheplapharm Arzneimittel Gmb H1998-06-18Not applicableAustria flag
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Hypertenevide-12.5Carvedilol (12.5 mg/1) + Arginine (60 mg/1)KitOralPhysician Therapeutics Llc2011-07-07Not applicableUS flag

Categories

ATC Codes
C07AG02 — CarvedilolC07FX06 — Carvedilol and ivabradine
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as carbazoles. These are compounds containing a three ring system containing a pyrrole ring fused on either side to a benzene ring.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Indoles and derivatives
Sub Class
Carbazoles
Direct Parent
Carbazoles
Alternative Parents
Indoles / Phenoxy compounds / Methoxybenzenes / Anisoles / Alkyl aryl ethers / Pyrroles / Heteroaromatic compounds / Secondary alcohols / 1,2-aminoalcohols / Dialkylamines
show 3 more
Substituents
1,2-aminoalcohol / Alcohol / Alkyl aryl ether / Amine / Anisole / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Carbazole / Ether
show 16 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
secondary alcohol, secondary amino compound, carbazoles (CHEBI:3441)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
0K47UL67F2
CAS number
72956-09-3
InChI Key
OGHNVEJMJSYVRP-UHFFFAOYSA-N
InChI
InChI=1S/C24H26N2O4/c1-28-21-10-4-5-11-22(21)29-14-13-25-15-17(27)16-30-23-12-6-9-20-24(23)18-7-2-3-8-19(18)26-20/h2-12,17,25-27H,13-16H2,1H3
IUPAC Name
1-(9H-carbazol-4-yloxy)-3-{[2-(2-methoxyphenoxy)ethyl]amino}propan-2-ol
SMILES
COC1=CC=CC=C1OCCNCC(O)COC1=CC=CC2=C1C1=CC=CC=C1N2

References

Synthesis Reference

Ilan Kor, "Crystalline solids of carvedilol and processes for their preparation." U.S. Patent US20030166702, issued September 04, 2003.

US20030166702
General References
  1. Vanderhoff BT, Ruppel HM, Amsterdam PB: Carvedilol: the new role of beta blockers in congestive heart failure. Am Fam Physician. 1998 Nov 1;58(7):1627-34, 1641-2. [Article]
  2. Oldham HG, Clarke SE: In vitro identification of the human cytochrome P450 enzymes involved in the metabolism of R(+)- and S(-)-carvedilol. Drug Metab Dispos. 1997 Aug;25(8):970-7. [Article]
  3. Takekuma Y, Yagisawa K, Sugawara M: Mutual inhibition between carvedilol enantiomers during racemate glucuronidation mediated by human liver and intestinal microsomes. Biol Pharm Bull. 2012;35(2):151-63. doi: 10.1248/bpb.35.151. [Article]
  4. Morgan T: Clinical pharmacokinetics and pharmacodynamics of carvedilol. Clin Pharmacokinet. 1994 May;26(5):335-46. doi: 10.2165/00003088-199426050-00002. [Article]
  5. FDA Approved Drug Products: Carvedilol Oral Tablets [Link]
  6. FDA Approved Drug Products: Carvedilol Oral Extended Release Capsules [Link]
Human Metabolome Database
HMDB0015267
KEGG Drug
D00255
KEGG Compound
C06875
PubChem Compound
2585
PubChem Substance
46505146
ChemSpider
2487
BindingDB
25759
RxNav
20352
ChEBI
3441
ChEMBL
CHEMBL723
Therapeutic Targets Database
DAP000135
PharmGKB
PA448817
Guide to Pharmacology
GtP Drug Page
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Carvedilol
FDA label
Download (1.25 MB)
MSDS
Download (32.9 KB)

Clinical Trials

Clinical Trials

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Actavis Group
  • Advantage Dose LLC
  • Amerisource Health Services Corp.
  • Apotex Inc.
  • A-S Medication Solutions LLC
  • Atlantic Biologicals Corporation
  • Aurobindo Pharma Ltd.
  • Bryant Ranch Prepack
  • Cadila Healthcare Ltd.
  • Caraco Pharmaceutical Labs
  • Cardinal Health
  • Caremark LLC
  • Dept Health Central Pharmacy
  • DHHS Program Support Center Supply Service Center
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Doctor Reddys Laboratories Ltd.
  • GlaxoSmithKline Inc.
  • Glenmark Generics Ltd.
  • Hikma Pharmaceuticals
  • Kaiser Foundation Hospital
  • Lupin Pharmaceuticals Inc.
  • Major Pharmaceuticals
  • Mckesson Corp.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mylan
  • Ohm Laboratories Inc.
  • Patheon Inc.
  • PD-Rx Pharmaceuticals Inc.
  • Physicians Total Care Inc.
  • Prepak Systems Inc.
  • Ranbaxy Laboratories
  • Rebel Distributors Corp.
  • Remedy Repack
  • Resource Optimization and Innovation LLC
  • Sandoz
  • Shasun Chemicals & Drugs Ltd.
  • Solco Healthcare US LLC
  • Southwood Pharmaceuticals
  • Taro Pharmaceuticals USA
  • Teva Pharmaceutical Industries Ltd.
  • UDL Laboratories
  • Vangard Labs Inc.
  • West-Ward Pharmaceuticals
  • Zydus Pharmaceuticals
Dosage Forms
FormRouteStrength
TabletOral
TabletOral25.000 mg
TabletOral1250000 mg
TabletOral2500000 mg
Tablet, film coatedOral
Tablet, film coatedOral12.5 MG
Tablet, film coatedOral25 MG
Tablet, film coatedOral6.25 MG
TabletOral12.5 mg/1
TabletOral25 mg/1
TabletOral25.0 mg
TabletOral3.125 mg/1
TabletOral6.25 mg/1
Tablet, coatedOral12.5 mg/1
Tablet, coatedOral25 mg/1
Tablet, coatedOral3.125 mg/1
Tablet, coatedOral6.25 mg/1
Tablet, film coatedOral12.5 mg/301
Tablet, film coatedOral12.5 mg/1
Tablet, film coatedOral25 mg/1
Tablet, film coatedOral3.125 mg/1
Tablet, film coatedOral6.25 mg/1
TabletOral
Tablet, film coatedOral
Tablet, coatedOral12.5 mg
Tablet, coatedOral2500000 mg
Tablet, coatedOral6.25 mg
Tablet, film coatedOral3.125 MG
TabletOral3125 MG
Tablet, film coatedOral3125 MG
TabletOral25 MG
Capsule, extended releaseOral10 mg/1
Capsule, extended releaseOral20 mg/1
Capsule, extended releaseOral40 mg/1
Capsule, extended releaseOral80 mg/1
TabletOral50 mg
TabletOral625000 mg
KitOral
TabletOral3.125 mg
Tablet, coatedOral25 mg
Tablet, film coatedOral12.500 mg
Tablet, film coatedOral25.000 mg
Tablet, film coatedOral6.250 mg
TabletOral12.5 mg
TabletOral6.25 mg
Prices
Unit descriptionCostUnit
Coreg CR 10 mg 24 Hour Capsule4.77USD capsule
Coreg CR 20 mg 24 Hour Capsule4.77USD capsule
Coreg CR 40 mg 24 Hour Capsule4.77USD capsule
Coreg CR 80 mg 24 Hour Capsule4.77USD capsule
Coreg cr 10 mg capsule4.59USD capsule
Coreg cr 20 mg capsule4.59USD capsule
Coreg cr 40 mg capsule4.59USD capsule
Coreg cr 80 mg capsule4.59USD capsule
Coreg 12.5 mg tablet2.54USD tablet
Coreg 25 mg tablet2.54USD tablet
Coreg 3.125 mg tablet2.54USD tablet
Coreg 6.25 mg tablet2.54USD tablet
Carvedilol 12.5 mg tablet2.18USD tablet
Carvedilol 25 mg tablet2.18USD tablet
Carvedilol 3.125 mg tablet2.18USD tablet
Carvedilol 6.25 mg tablet2.18USD tablet
Apo-Carvedilol 12.5 mg Tablet0.84USD tablet
Apo-Carvedilol 25 mg Tablet0.84USD tablet
Apo-Carvedilol 3.125 mg Tablet0.84USD tablet
Apo-Carvedilol 6.25 mg Tablet0.84USD tablet
Phl-Carvedilol 12.5 mg Tablet0.79USD tablet
Phl-Carvedilol 3.125 mg Tablet0.79USD tablet
Phl-Carvedilol 6.25 mg Tablet0.79USD tablet
Pms-Carvedilol 12.5 mg Tablet0.79USD tablet
Pms-Carvedilol 25 mg Tablet0.79USD tablet
Pms-Carvedilol 3.125 mg Tablet0.79USD tablet
Pms-Carvedilol 6.25 mg Tablet0.79USD tablet
Ran-Carvedilol 12.5 mg Tablet0.79USD tablet
Ran-Carvedilol 25 mg Tablet0.79USD tablet
Ran-Carvedilol 3.125 mg Tablet0.79USD tablet
Ran-Carvedilol 6.25 mg Tablet0.79USD tablet
Ratio-Carvedilol 12.5 mg Tablet0.79USD tablet
Ratio-Carvedilol 25 mg Tablet0.79USD tablet
Ratio-Carvedilol 3.125 mg Tablet0.79USD tablet
Ratio-Carvedilol 6.25 mg Tablet0.79USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US7268156Yes2007-09-112023-12-27US flag
US8101209Yes2012-01-242026-03-11US flag
US6022562Yes2000-02-082016-04-17US flag
USRE40000Yes2008-01-082015-12-07US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)114.5 °Chttp://www.chemspider.com/Chemical-Structure.2487.html
water solubility88mg/mLhttp://www.chemspider.com/Chemical-Structure.2487.html
logP3.8https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361727/
Predicted Properties
PropertyValueSource
Water Solubility0.00444 mg/mLALOGPS
logP3.05ALOGPS
logP3.42Chemaxon
logS-5ALOGPS
pKa (Strongest Acidic)14.03Chemaxon
pKa (Strongest Basic)8.74Chemaxon
Physiological Charge1Chemaxon
Hydrogen Acceptor Count5Chemaxon
Hydrogen Donor Count3Chemaxon
Polar Surface Area75.74 Å2Chemaxon
Rotatable Bond Count10Chemaxon
Refractivity115.64 m3·mol-1Chemaxon
Polarizability45.03 Å3Chemaxon
Number of Rings4Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleYesChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9706
Blood Brain Barrier-0.6814
Caco-2 permeable-0.6308
P-glycoprotein substrateSubstrate0.8552
P-glycoprotein inhibitor INon-inhibitor0.8729
P-glycoprotein inhibitor IINon-inhibitor0.6521
Renal organic cation transporterNon-inhibitor0.5405
CYP450 2C9 substrateNon-substrate0.7517
CYP450 2D6 substrateSubstrate0.8918
CYP450 3A4 substrateSubstrate0.5408
CYP450 1A2 substrateInhibitor0.524
CYP450 2C9 inhibitorNon-inhibitor0.8496
CYP450 2D6 inhibitorNon-inhibitor0.7274
CYP450 2C19 inhibitorNon-inhibitor0.5676
CYP450 3A4 inhibitorNon-inhibitor0.6352
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6048
Ames testNon AMES toxic0.8261
CarcinogenicityNon-carcinogens0.9692
BiodegradationNot ready biodegradable0.963
Rat acute toxicity2.4566 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.5725
hERG inhibition (predictor II)Inhibitor0.8889
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-001j-2930000000-265c376e802c07cf1f2d
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0a4i-1662900000-f901a62f255da92e9a09
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0a4i-0220900000-5821022307fc5077033b
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0540-0191400000-6ca107cb7cfb8a8df480
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-001i-1920100000-260ea815e32284b67e6e
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0uyi-0692100000-94603f19885f76f25d91
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-001i-0910000000-fdc780b7f84ab5fc815b
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0c0r-3921000000-87acb72afee99d28a2e1
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-001i-0900000000-6537a5cf26732e4e5abf
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-198.3687664
predicted
DarkChem Lite v0.1.0
[M-H]-183.00732
predicted
DeepCCS 1.0 (2019)
[M+H]+198.7501664
predicted
DarkChem Lite v0.1.0
[M+H]+185.36533
predicted
DeepCCS 1.0 (2019)
[M+Na]+198.3830664
predicted
DarkChem Lite v0.1.0
[M+Na]+193.39514
predicted
DeepCCS 1.0 (2019)

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Receptor signaling protein activity
Specific Function
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately e...
Gene Name
ADRB1
Uniprot ID
P08588
Uniprot Name
Beta-1 adrenergic receptor
Molecular Weight
51322.1 Da
References
  1. Nichols AJ, Gellai M, Ruffolo RR Jr: Studies on the mechanism of arterial vasodilation produced by the novel antihypertensive agent, carvedilol. Fundam Clin Pharmacol. 1991;5(1):25-38. [Article]
  2. Nichols AJ, Sulpizio AC, Ashton DJ, Hieble JP, Ruffolo RR Jr: In vitro pharmacologic profile of the novel beta-adrenoceptor antagonist and vasodilator, carvedilol. Pharmacology. 1989;39(5):327-36. [Article]
  3. Nichols AJ, Sulpizio AC, Ashton DJ, Hieble JP, Ruffolo RR Jr: The interaction of the enantiomers of carvedilol with alpha 1- and beta 1-adrenoceptors. Chirality. 1989;1(4):265-70. [Article]
  4. de Mey C, Breithaupt K, Schloos J, Neugebauer G, Palm D, Belz GG: Dose-effect and pharmacokinetic-pharmacodynamic relationships of the beta 1-adrenergic receptor blocking properties of various doses of carvedilol in healthy humans. Clin Pharmacol Ther. 1994 Mar;55(3):329-37. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
Potentiator
Curator comments
This drug is a non-selective alpha antagonist.
General Function
Protein heterodimerization activity
Specific Function
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
Gene Name
ADRA1A
Uniprot ID
P35348
Uniprot Name
Alpha-1A adrenergic receptor
Molecular Weight
51486.005 Da
References
  1. O'Connell TD, Jensen BC, Baker AJ, Simpson PC: Cardiac alpha1-adrenergic receptors: novel aspects of expression, signaling mechanisms, physiologic function, and clinical importance. Pharmacol Rev. 2013 Dec 24;66(1):308-33. doi: 10.1124/pr.112.007203. Print 2014. [Article]
  2. Jensen BC, Swigart PM, De Marco T, Hoopes C, Simpson PC: {alpha}1-Adrenergic receptor subtypes in nonfailing and failing human myocardium. Circ Heart Fail. 2009 Nov;2(6):654-63. doi: 10.1161/CIRCHEARTFAILURE.108.846212. Epub 2009 Aug 6. [Article]
Kind
Protein group
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Protein heterodimerization activity
Specific Function
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...

Components:
References
  1. O'Connell TD, Jensen BC, Baker AJ, Simpson PC: Cardiac alpha1-adrenergic receptors: novel aspects of expression, signaling mechanisms, physiologic function, and clinical importance. Pharmacol Rev. 2013 Dec 24;66(1):308-33. doi: 10.1124/pr.112.007203. Print 2014. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Nadh dehydrogenase (ubiquinone) activity
Specific Function
Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons ...
Gene Name
NDUFC2
Uniprot ID
O95298
Uniprot Name
NADH dehydrogenase [ubiquinone] 1 subunit C2
Molecular Weight
14187.33 Da
References
  1. Oliveira PJ, Santos DJ, Moreno AJ: Carvedilol inhibits the exogenous NADH dehydrogenase in rat heart mitochondria. Arch Biochem Biophys. 2000 Feb 15;374(2):279-85. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
General Function
Protein homodimerization activity
Specific Function
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately ...
Gene Name
ADRB2
Uniprot ID
P07550
Uniprot Name
Beta-2 adrenergic receptor
Molecular Weight
46458.32 Da
References
  1. Irodova NL, Krasnikova TL, Masenko VP, Kochetov AG, Chazova IE: [Carvedilol in treating primary pulmonary hypertension patients: effect on severity of cardiac failure, degree of pulmonary hypertension, concentration of catecholamines in blood plasma and dependence of cyclic AMP synthesis in lymphocytes on beta-adrenergic receptors]. Ter Arkh. 2002;74(8):30-4. [Article]
  2. Maebara C, Ohtani H, Sugahara H, Mine K, Kubo C, Sawada Y: Nightmares and panic disorder associated with carvedilol overdose. Ann Pharmacother. 2002 Nov;36(11):1736-40. [Article]
  3. Okajima K, Harada N, Uchiba M, Isobe H: Activation of capsaicin-sensitive sensory neurons by carvedilol, a nonselective beta-blocker, in spontaneous hypertensive rats. J Pharmacol Exp Ther. 2004 May;309(2):684-91. Epub 2004 Feb 5. [Article]
  4. Nichols AJ, Gellai M, Ruffolo RR Jr: Studies on the mechanism of arterial vasodilation produced by the novel antihypertensive agent, carvedilol. Fundam Clin Pharmacol. 1991;5(1):25-38. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Other
General Function
Vascular endothelial growth factor receptor binding
Specific Function
Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilization of...
Gene Name
VEGFA
Uniprot ID
P15692
Uniprot Name
Vascular endothelial growth factor A
Molecular Weight
27042.205 Da
References
  1. de Boer RA, Siebelink HJ, Tio RA, Boomsma F, van Veldhuisen DJ: Carvedilol increases plasma vascular endothelial growth factor (VEGF) in patients with chronic heart failure. Eur J Heart Fail. 2001 Jun;3(3):331-3. [Article]
  2. Saijonmaa O, Nyman T, Fyhrquist F: Carvedilol inhibits basal and stimulated ACE production in human endothelial cells. J Cardiovasc Pharmacol. 2004 May;43(5):616-21. [Article]
  3. Shyu KG, Lu MJ, Chang H, Sun HY, Wang BW, Kuan P: Carvedilol modulates the expression of hypoxia-inducible factor-1alpha and vascular endothelial growth factor in a rat model of volume-overload heart failure. J Card Fail. 2005 Mar;11(2):152-9. [Article]
  4. Shyu KG, Liou JY, Wang BW, Fang WJ, Chang H: Carvedilol prevents cardiac hypertrophy and overexpression of hypoxia-inducible factor-1alpha and vascular endothelial growth factor in pressure-overloaded rat heart. J Biomed Sci. 2005;12(2):409-20. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Other
General Function
Receptor binding
Specific Function
Cardiac hormone which may function as a paracrine antifibrotic factor in the heart. Also plays a key role in cardiovascular homeostasis through natriuresis, diuresis, vasorelaxation, and inhibition...
Gene Name
NPPB
Uniprot ID
P16860
Uniprot Name
Natriuretic peptides B
Molecular Weight
14725.825 Da
References
  1. Ohta Y, Watanabe K, Nakazawa M, Yamamoto T, Ma M, Fuse K, Ito M, Hirono S, Tanabe T, Hanawa H, Kato K, Kodama M, Aizawa Y: Carvedilol enhances atrial and brain natriuretic peptide mRNA expression and release in rat heart. J Cardiovasc Pharmacol. 2000;36 Suppl 2:S19-23. [Article]
  2. Richards AM, Doughty R, Nicholls MG, MacMahon S, Sharpe N, Murphy J, Espiner EA, Frampton C, Yandle TG: Plasma N-terminal pro-brain natriuretic peptide and adrenomedullin: prognostic utility and prediction of benefit from carvedilol in chronic ischemic left ventricular dysfunction. Australia-New Zealand Heart Failure Group. J Am Coll Cardiol. 2001 Jun 1;37(7):1781-7. [Article]
  3. Konishi H, Nishio S, Tsutamoto T, Minouchi T, Yamaji A: Serum carvedilol concentration and its relation to change in plasma brain natriuretic peptide level in the treatment of heart failure: a preliminary study. Int J Clin Pharmacol Ther. 2003 Dec;41(12):578-86. [Article]
  4. Takeda Y, Fukutomi T, Suzuki S, Yamamoto K, Ogata M, Kondo H, Sugiura M, Shigeyama J, Itoh M: Effects of carvedilol on plasma B-type natriuretic peptide concentration and symptoms in patients with heart failure and preserved ejection fraction. Am J Cardiol. 2004 Aug 15;94(4):448-53. [Article]
  5. Frantz RP, Olson LJ, Grill D, Moualla SK, Nelson SM, Nobrega TP, Hanna RD, Backes RJ, Mookadam F, Heublein D, Bailey KR, Burnett JC: Carvedilol therapy is associated with a sustained decline in brain natriuretic peptide levels in patients with congestive heart failure. Am Heart J. 2005 Mar;149(3):541-7. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Other
General Function
Signal transducer activity
Specific Function
Gap junction protein that acts as a regulator of bladder capacity. A gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of ...
Gene Name
GJA1
Uniprot ID
P17302
Uniprot Name
Gap junction alpha-1 protein
Molecular Weight
43008.005 Da
References
  1. Yeh HI, Lee PY, Su CH, Tian TY, Ko YS, Tsai CH: Reduced expression of endothelial connexins 43 and 37 in hypertensive rats is rectified after 7-day carvedilol treatment. Am J Hypertens. 2006 Feb;19(2):129-35. [Article]
  2. Fan SY, Ke YN, Zeng YJ, Wang Y, Cheng WL, Yang JR: [Effects and the mechanism of carvedilol on gap junctional intercellular communication in rat myocardium]. Zhonghua Xin Xue Guan Bing Za Zhi. 2005 Dec;33(12):1141-5. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization
Specific Function
Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the ...
Gene Name
KCNH2
Uniprot ID
Q12809
Uniprot Name
Potassium voltage-gated channel subfamily H member 2
Molecular Weight
126653.52 Da
References
  1. Karle CA, Kreye VA, Thomas D, Rockl K, Kathofer S, Zhang W, Kiehn J: Antiarrhythmic drug carvedilol inhibits HERG potassium channels. Cardiovasc Res. 2001 Feb 1;49(2):361-70. [Article]
  2. Kawakami K, Nagatomo T, Abe H, Kikuchi K, Takemasa H, Anson BD, Delisle BP, January CT, Nakashima Y: Comparison of HERG channel blocking effects of various beta-blockers-- implication for clinical strategy. Br J Pharmacol. 2006 Mar;147(6):642-52. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Primary amine oxidase activity
Specific Function
Important in cell-cell recognition. Appears to function in leukocyte-endothelial cell adhesion. Interacts with integrin alpha-4/beta-1 (ITGA4/ITGB1) on leukocytes, and mediates both adhesion and si...
Gene Name
VCAM1
Uniprot ID
P19320
Uniprot Name
Vascular cell adhesion protein 1
Molecular Weight
81275.43 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
  3. Chen JW, Lin FY, Chen YH, Wu TC, Chen YL, Lin SJ: Carvedilol inhibits tumor necrosis factor-alpha-induced endothelial transcription factor activation, adhesion molecule expression, and adhesiveness to human mononuclear cells. Arterioscler Thromb Vasc Biol. 2004 Nov;24(11):2075-81. Epub 2004 Sep 16. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
General Function
Alpha1-adrenergic receptor activity
Specific Function
This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium.
Gene Name
ADRA1D
Uniprot ID
P25100
Uniprot Name
Alpha-1D adrenergic receptor
Molecular Weight
60462.205 Da
References
  1. Koshimizu TA, Tsujimoto G, Hirasawa A, Kitagawa Y, Tanoue A: Carvedilol selectively inhibits oscillatory intracellular calcium changes evoked by human alpha1D- and alpha1B-adrenergic receptors. Cardiovasc Res. 2004 Sep 1;63(4):662-72. [Article]
  2. Van Tassell BW, Rondina MT, Huggins F, Gilbert EM, Munger MA: Carvedilol increases blood pressure response to phenylephrine infusion in heart failure subjects with systolic dysfunction: evidence of improved vascular alpha1-adrenoreceptor signal transduction. Am Heart J. 2008 Aug;156(2):315-21. doi: 10.1016/j.ahj.2008.04.004. Epub 2008 Jun 20. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
General Function
Protein heterodimerization activity
Specific Function
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
Gene Name
ADRA1B
Uniprot ID
P35368
Uniprot Name
Alpha-1B adrenergic receptor
Molecular Weight
56835.375 Da
References
  1. Koshimizu TA, Tsujimoto G, Hirasawa A, Kitagawa Y, Tanoue A: Carvedilol selectively inhibits oscillatory intracellular calcium changes evoked by human alpha1D- and alpha1B-adrenergic receptors. Cardiovasc Res. 2004 Sep 1;63(4):662-72. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
General Function
Protein homodimerization activity
Specific Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins.
Gene Name
ADRA2C
Uniprot ID
P18825
Uniprot Name
Alpha-2C adrenergic receptor
Molecular Weight
49521.585 Da
References
  1. Koshimizu TA, Tsujimoto G, Hirasawa A, Kitagawa Y, Tanoue A: Carvedilol selectively inhibits oscillatory intracellular calcium changes evoked by human alpha1D- and alpha1B-adrenergic receptors. Cardiovasc Res. 2004 Sep 1;63(4):662-72. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
General Function
Epinephrine binding
Specific Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is clonidine...
Gene Name
ADRA2B
Uniprot ID
P18089
Uniprot Name
Alpha-2B adrenergic receptor
Molecular Weight
49565.8 Da
References
  1. Koshimizu TA, Tsujimoto G, Hirasawa A, Kitagawa Y, Tanoue A: Carvedilol selectively inhibits oscillatory intracellular calcium changes evoked by human alpha1D- and alpha1B-adrenergic receptors. Cardiovasc Res. 2004 Sep 1;63(4):662-72. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
General Function
Thioesterase binding
Specific Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazo...
Gene Name
ADRA2A
Uniprot ID
P08913
Uniprot Name
Alpha-2A adrenergic receptor
Molecular Weight
48956.275 Da
References
  1. Koshimizu TA, Tsujimoto G, Hirasawa A, Kitagawa Y, Tanoue A: Carvedilol selectively inhibits oscillatory intracellular calcium changes evoked by human alpha1D- and alpha1B-adrenergic receptors. Cardiovasc Res. 2004 Sep 1;63(4):662-72. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transmembrane signaling receptor activity
Specific Function
Cell-surface glycoprotein having a role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with PSGL1/SELPLG. May have a role in ...
Gene Name
SELE
Uniprot ID
P16581
Uniprot Name
E-selectin
Molecular Weight
66654.575 Da
References
  1. Chen JW, Lin FY, Chen YH, Wu TC, Chen YL, Lin SJ: Carvedilol inhibits tumor necrosis factor-alpha-induced endothelial transcription factor activation, adhesion molecule expression, and adhesiveness to human mononuclear cells. Arterioscler Thromb Vasc Biol. 2004 Nov;24(11):2075-81. Epub 2004 Sep 16. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Modulator
General Function
Ubiquitin protein ligase binding
Specific Function
Functions as a master transcriptional regulator of the adaptive response to hypoxia. Under hypoxic conditions, activates the transcription of over 40 genes, including erythropoietin, glucose transp...
Gene Name
HIF1A
Uniprot ID
Q16665
Uniprot Name
Hypoxia-inducible factor 1-alpha
Molecular Weight
92669.595 Da
References
  1. Shyu KG, Lu MJ, Chang H, Sun HY, Wang BW, Kuan P: Carvedilol modulates the expression of hypoxia-inducible factor-1alpha and vascular endothelial growth factor in a rat model of volume-overload heart failure. J Card Fail. 2005 Mar;11(2):152-9. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Pdz domain binding
Specific Function
Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentratio...
Gene Name
KCNJ4
Uniprot ID
P48050
Uniprot Name
Inward rectifier potassium channel 4
Molecular Weight
49499.61 Da
References
  1. Ferrer T, Ponce-Balbuena D, Lopez-Izquierdo A, Arechiga-Figueroa IA, de Boer TP, van der Heyden MA, Sanchez-Chapula JA: Carvedilol inhibits Kir2.3 channels by interference with PIP(2)-channel interaction. Eur J Pharmacol. 2011 Oct 1;668(1-2):72-7. doi: 10.1016/j.ejphar.2011.05.067. Epub 2011 Jun 6. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Probably participates in establishing action potential waveform and excitability of neuronal and muscle tissues. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by extracellular barium or cesium.
Specific Function
Identical protein binding
Gene Name
KCNJ2
Uniprot ID
P63252
Uniprot Name
Inward rectifier potassium channel 2
Molecular Weight
48287.82 Da
References
  1. Ferrer T, Ponce-Balbuena D, Lopez-Izquierdo A, Arechiga-Figueroa IA, de Boer TP, van der Heyden MA, Sanchez-Chapula JA: Carvedilol inhibits Kir2.3 channels by interference with PIP(2)-channel interaction. Eur J Pharmacol. 2011 Oct 1;668(1-2):72-7. doi: 10.1016/j.ejphar.2011.05.067. Epub 2011 Jun 6. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
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 un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Oldham HG, Clarke SE: In vitro identification of the human cytochrome P450 enzymes involved in the metabolism of R(+)- and S(-)-carvedilol. Drug Metab Dispos. 1997 Aug;25(8):970-7. [Article]
  2. Parker BM, Rogers SL, Lymperopoulos A: Clinical pharmacogenomics of carvedilol: the stereo-selective metabolism angle. Pharmacogenomics. 2018 Sep 1;19(14):1089-1093. doi: 10.2217/pgs-2018-0115. Epub 2018 Aug 8. [Article]
  3. Abrudan MB, Popa DS, Muntean DM, Gheldiu AM, Vlase L: Pharmacokinetic interactions study between carvedilol and some antidepressants in rat liver microsomes - a comparative study. Med Pharm Rep. 2019 Apr;92(2):158-164. doi: 10.15386/mpr-1225. Epub 2019 Apr 25. [Article]
  4. FDA label, Carvedilol [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase 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 react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Wang Z, Wang L, Xu RA, Zhan YY, Huang CK, Dai DP, Cai JP, Hu GX: Role of cytochrome P450 2D6 genetic polymorphism in carvedilol hydroxylation in vitro. Drug Des Devel Ther. 2016 Jun 8;10:1909-16. doi: 10.2147/DDDT.S106175. eCollection 2016. [Article]
  2. Oldham HG, Clarke SE: In vitro identification of the human cytochrome P450 enzymes involved in the metabolism of R(+)- and S(-)-carvedilol. Drug Metab Dispos. 1997 Aug;25(8):970-7. [Article]
  3. Carvedilol Therapy and CYP2D6 Genotype [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d 24-hydroxylase 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 un...
Gene Name
CYP1A1
Uniprot ID
P04798
Uniprot Name
Cytochrome P450 1A1
Molecular Weight
58164.815 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
Gene Name
CYP2E1
Uniprot ID
P05181
Uniprot Name
Cytochrome P450 2E1
Molecular Weight
56848.42 Da
References
  1. Oldham HG, Clarke SE: In vitro identification of the human cytochrome P450 enzymes involved in the metabolism of R(+)- and S(-)-carvedilol. Drug Metab Dispos. 1997 Aug;25(8):970-7. [Article]
  2. Carvedilol Therapy and CYP2D6 Genotype [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Steroid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A1
Uniprot ID
P22309
Uniprot Name
UDP-glucuronosyltransferase 1-1
Molecular Weight
59590.91 Da
References
  1. Williams JA, Hyland R, Jones BC, Smith DA, Hurst S, Goosen TC, Peterkin V, Koup JR, Ball SE: Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos. 2004 Nov;32(11):1201-8. doi: 10.1124/dmd.104.000794. Epub 2004 Aug 10. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Glucuronosyltransferase activity
Specific Function
UDPGTs are of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isozyme is active on polyhydroxylated estrogens (such as...
Gene Name
UGT2B4
Uniprot ID
P06133
Uniprot Name
UDP-glucuronosyltransferase 2B4
Molecular Weight
60512.035 Da
References
  1. Williams JA, Hyland R, Jones BC, Smith DA, Hurst S, Goosen TC, Peterkin V, Koup JR, Ball SE: Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos. 2004 Nov;32(11):1201-8. doi: 10.1124/dmd.104.000794. Epub 2004 Aug 10. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Glucuronosyltransferase activity
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.Its unique specificity for 3,4-catechol estrogens and estriol su...
Gene Name
UGT2B7
Uniprot ID
P16662
Uniprot Name
UDP-glucuronosyltransferase 2B7
Molecular Weight
60694.12 Da
References
  1. Williams JA, Hyland R, Jones BC, Smith DA, Hurst S, Goosen TC, Peterkin V, Koup JR, Ball SE: Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos. 2004 Nov;32(11):1201-8. doi: 10.1124/dmd.104.000794. Epub 2004 Aug 10. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase 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 un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Pan PP, Weng QH, Zhou CJ, Wei YL, Wang L, Dai DP, Cai JP, Hu GX: The role of CYP2C9 genetic polymorphism in carvedilol O-desmethylation in vitro. Eur J Drug Metab Pharmacokinet. 2016 Feb;41(1):79-86. doi: 10.1007/s13318-014-0245-2. Epub 2014 Dec 5. [Article]
  2. Laura Dean, MD (2012). Medical Genetics Summaries : Carvedilol Therapy and CYP2D6 Genotype. National Center for Biotechnology Information (US).
  3. Carvedilol Therapy and CYP2D6 Genotype [Link]
  4. Carvedilol FDA [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase 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...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
  2. Flockhart Table of Drug Interactions [Link]
  3. Carvedilol Therapy and CYP2D6 Genotype [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Xanthine oxidase activity
Specific Function
Key enzyme in purine degradation. Catalyzes the oxidation of hypoxanthine to xanthine. Catalyzes the oxidation of xanthine to uric acid. Contributes to the generation of reactive oxygen species. Ha...
Gene Name
XDH
Uniprot ID
P47989
Uniprot Name
Xanthine dehydrogenase/oxidase
Molecular Weight
146422.99 Da
References
  1. Yue TL, McKenna PJ, Gu JL, Cheng HY, Ruffolo RE Jr, Feuerstein GZ: Carvedilol, a new vasodilating beta adrenoceptor blocker antihypertensive drug, protects endothelial cells from damage initiated by xanthine-xanthine oxidase and neutrophils. Cardiovasc Res. 1994 Mar;28(3):400-6. [Article]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. FDA Approved Drug Products: Carvedilol Oral Tablets [Link]
  2. FDA Approved Drug Products: Carvedilol Oral Extended Release Capsules [Link]

Transporters

Details
1. P-glycoprotein 1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
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. [Article]
  2. Takara K, Kakumoto M, Tanigawara Y, Funakoshi J, Sakaeda T, Okumura K: Interaction of digoxin with antihypertensive drugs via MDR1. Life Sci. 2002 Feb 15;70(13):1491-500. [Article]
  3. Jonsson O, Behnam-Motlagh P, Persson M, Henriksson R, Grankvist K: Increase in doxorubicin cytotoxicity by carvedilol inhibition of P-glycoprotein activity. Biochem Pharmacol. 1999 Dec 1;58(11):1801-6. [Article]
  4. Neuhoff S, Langguth P, Dressler C, Andersson TB, Regardh CG, Spahn-Langguth H: Affinities at the verapamil binding site of MDR1-encoded P-glycoprotein: drugs and analogs, stereoisomers and metabolites. Int J Clin Pharmacol Ther. 2000 Apr;38(4):168-79. [Article]
  5. Hokama N, Hobara N, Sakai M, Kameya H, Ohshiro S, Sakanashi M: Influence of nicardipine and nifedipine on plasma carvedilol disposition after oral administration in rats. J Pharm Pharmacol. 2002 Jun;54(6):821-5. [Article]
  6. Kakumoto M, Sakaeda T, Takara K, Nakamura T, Kita T, Yagami T, Kobayashi H, Okamura N, Okumura K: Effects of carvedilol on MDR1-mediated multidrug resistance: comparison with verapamil. Cancer Sci. 2003 Jan;94(1):81-6. [Article]
  7. Brodde OE, Kroemer HK: Drug-drug interactions of beta-adrenoceptor blockers. Arzneimittelforschung. 2003;53(12):814-22. [Article]
  8. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]

Drug created at June 13, 2005 13:24 / Updated at March 18, 2024 16:48