Identification

Name
Carvedilol
Accession Number
DB01136  (APRD00091)
Type
Small Molecule
Groups
Approved, Investigational
Description

Carvedilol is a non-selective beta blocker indicated in the treatment of mild to moderate congestive heart failure (CHF). It blocks beta-1 and beta-2 adrenergic receptors as well as the alpha-1 adrenergic receptors.

Structure
Thumb
Synonyms
  • (+-)-1-(Carbazol-4-yloxy)-3-((2-(O-methoxyphenoxy)ethyl)amino)-2-propanol
  • Carvedilol
  • Carvedilolum
  • SKF 105517
Product Ingredients
IngredientUNIICASInChI Key
Carvedilol phosphateEQT531S367610309-89-2LHNYXTULDSJZRB-UHFFFAOYSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CarvedilolTablet25.0 mgOralPro Doc Limitee2009-06-12Not applicableCanada
CarvedilolTablet3.125 mgOralMeliapharm Inc2010-06-012014-06-25Canada
CarvedilolTablet, coated6.25 mg/1OralRanbaxy Inc.2007-10-06Not applicableUs
CarvedilolTablet3.125 mgOralPro Doc Limitee2009-06-12Not applicableCanada
CarvedilolTablet25 mgOralSivem Pharmaceuticals Ulc2004-04-06Not applicableCanada
CarvedilolTablet3.125 mgOralSivem Pharmaceuticals Ulc2004-04-06Not applicableCanada
CarvedilolTablet6.25 mgOralSanis Health Inc2011-06-10Not applicableCanada
CarvedilolTablet12.5 mgOralMeliapharm Inc2010-05-172014-06-25Canada
CarvedilolTablet, coated25 mg/1OralRanbaxy Inc.2007-10-06Not applicableUs
CarvedilolTablet12.5 mgOralPro Doc Limitee2009-06-12Not applicableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-carvedilolTablet6.25 mgOralApotex Corporation2003-08-06Not applicableCanada
Apo-carvedilolTablet25 mgOralApotex Corporation2003-08-06Not applicableCanada
Apo-carvedilolTablet3.125 mgOralApotex Corporation2003-08-06Not applicableCanada
Apo-carvedilolTablet12.5 mgOralApotex Corporation2003-08-06Not applicableCanada
Auro-carvedilolTablet6.25 mgOralAuro Pharma Inc2014-02-06Not applicableCanada
Auro-carvedilolTablet25 mgOralAuro Pharma Inc2014-02-06Not applicableCanada
Auro-carvedilolTablet3.125 mgOralAuro Pharma Inc2014-02-06Not applicableCanada
Auro-carvedilolTablet12.5 mgOralAuro Pharma Inc2014-02-06Not applicableCanada
Ava-carvedilolTablet3.125 mgOralAvanstra Inc2011-10-112014-08-21Canada
Ava-carvedilolTablet12.5 mgOralAvanstra Inc2011-10-112014-08-21Canada
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Hypertenevide-12.5Carvedilol (12.5 mg/1) + L-Arginine (60 mg/1)KitPhysician Therapeutics Llc2011-07-07Not applicableUs
International/Other Brands
COREGCR
Categories
UNII
0K47UL67F2
CAS number
72956-09-3
Weight
Average: 406.4742
Monoisotopic: 406.18925733
Chemical Formula
C24H26N2O4
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

Pharmacology

Indication

For the treatment of mild or moderate (NYHA class II or III) heart failure of ischemic or cardiomyopathic origin.

Associated Conditions
Pharmacodynamics

Carvedilol is a nonselective beta-adrenergic blocking agent with alpha1-blocking activity and is indicated for the treatment of hypertension and mild or moderate (NYHA class II or III) heart failure of ischemic or cardiomyopathic origin. Carvedilol is a racemic mixture in which nonselective b-adrenoreceptor blocking activity is present in the S(-) enantiomer and a-adrenergic blocking activity is present in both R(+) and S(-) enantiomers at equal potency. Carvedilol has no intrinsic sympathomimetic activity. The effect of carvedilol's b-adrenoreceptor blocking activity has been demonstrated in animal and human studies showing that carvedilol (1) reduces cardiac output in normal subjects; (2) reduces exercise-and/or isoproterenol-induced tachycardia and (3) reduces reflex orthostatic tachycardia.

Mechanism of action

Carvedilol is a racemic mixture in which nonselective beta-adrenoreceptor blocking activity is present in the S(-) enantiomer and alpha-adrenergic blocking activity is present in both R(+) and S(-) enantiomers at equal potency. Carvedilol's beta-adrenergic receptor blocking ability decreases the heart rate, myocardial contractility, and myocardial oxygen demand. Carvedilol also decreases systemic vascular resistance via its alpha adrenergic receptor blocking properties. Carvedilol and its metabolite BM-910228 (a less potent beta blocker, but more potent antioxidant) have been shown to restore the inotropic responsiveness to Ca2+ in OH- free radical-treated myocardium. Carvedilol and its metabolites also prevent OH- radical-induced decrease in sarcoplasmic reticulum Ca2+-ATPase activity. Therefore, carvedilol and its metabolites may be beneficial in chronic heart failure by preventing free radical damage.

TargetActionsOrganism
ABeta-1 adrenergic receptor
antagonist
Human
AAlpha-1A adrenergic receptor
antagonist
Human
UNADH dehydrogenase [ubiquinone] 1 subunit C2
inhibitor
Human
UBeta-2 adrenergic receptor
antagonist
Human
UVascular endothelial growth factor A
other
Human
UNatriuretic peptides B
other
Human
UGap junction alpha-1 protein
other
Human
UPotassium voltage-gated channel subfamily H member 2
inhibitor
Human
UVascular cell adhesion protein 1
inhibitor
Human
UAlpha-1D adrenergic receptor
antagonist
Human
UAlpha-1B adrenergic receptor
antagonist
Human
UAlpha-2C adrenergic receptor
antagonist
Human
UAlpha-2B adrenergic receptor
antagonist
Human
UAlpha-2A adrenergic receptor
antagonist
Human
UE-selectin
inhibitor
Human
UHypoxia-inducible factor 1-alpha
modulator
Human
UInward rectifier potassium channel 4Not AvailableHuman
Absorption

Carvedilol is rapidly and extensively absorbed following oral administration, with an absolute bioavailability of approximately 25% to 35% due to a significant degree of first-pass metabolism.

Volume of distribution
  • 115 L
Protein binding

98%

Metabolism

Hepatic. Carvedilol is metabolized primarily by aromatic ring oxidation and glucuronidation. The oxidative metabolites are further metabolized by conjugation via glucuronidation and sulfation. Demethylation and hydroxylation at the phenol ring produce three active metabolites with b-receptor blocking activity. The 4'-hydroxyphenyl metabolite is approximately 13 times more potent than carvedilol for b-blockade.

Route of elimination

Carvedilol is extensively metabolized. Less than 2% of the dose was excreted unchanged in the urine. Carvedilol is metabolized primarily by aromatic ring oxidation and glucuronidation. The oxidative metabolites are further metabolized by conjugation via glucuronidation and sulfation. The metabolites of carvedilol are excreted primarily via the bile into the feces.

Half life

7-10 hours

Clearance
  • 500-700 mL/min
Toxicity

Not expected to be toxic following ingestion.

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Carvedilol Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Beta-1 adrenergic receptor---(A;A) / (C;C) / (C;G)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
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Carvedilol.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Carvedilol.
1,10-Phenanthroline1,10-Phenanthroline may increase the bradycardic activities of Carvedilol.
3-isobutyl-1-methyl-7H-xanthineThe serum concentration of 3-isobutyl-1-methyl-7H-xanthine can be increased when it is combined with Carvedilol.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Carvedilol.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Carvedilol.
4-MethoxyamphetamineThe therapeutic efficacy of 4-Methoxyamphetamine can be decreased when used in combination with Carvedilol.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Carvedilol.
6-Deoxyerythronolide BThe metabolism of Carvedilol can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe serum concentration of 6-O-benzylguanine can be increased when it is combined with Carvedilol.
Food Interactions
  • Take with food, food slows the absorption rate and reduces the incidence of adverse effects (extent of absorption is not affected).

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. Packer M, Fowler MB, Roecker EB, Coats AJ, Katus HA, Krum H, Mohacsi P, Rouleau JL, Tendera M, Staiger C, Holcslaw TL, Amann-Zalan I, DeMets DL: Effect of carvedilol on the morbidity of patients with severe chronic heart failure: results of the carvedilol prospective randomized cumulative survival (COPERNICUS) study. Circulation. 2002 Oct 22;106(17):2194-9. [PubMed:12390947]
  2. Packer M, Coats AJ, Fowler MB, Katus HA, Krum H, Mohacsi P, Rouleau JL, Tendera M, Castaigne A, Roecker EB, Schultz MK, DeMets DL: Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med. 2001 May 31;344(22):1651-8. [PubMed:11386263]
  3. 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. [PubMed:9824960]
External Links
Human Metabolome Database
HMDB0015267
KEGG Drug
D00255
KEGG Compound
C06875
PubChem Compound
2585
PubChem Substance
46505146
ChemSpider
2487
BindingDB
25759
ChEBI
3441
ChEMBL
CHEMBL723
Therapeutic Targets Database
DAP000135
PharmGKB
PA448817
IUPHAR
551
Guide to Pharmacology
GtP Drug Page
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Carvedilol
ATC Codes
C07AG02 — Carvedilol
AHFS Codes
  • 24:24.00 — Beta-adrenergic Blocking Agents
FDA label
Download (1.25 MB)
MSDS
Download (32.9 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingBasic ScienceSleep / Sleep Deprivation / Sleep Wake Disorders1
1CompletedNot AvailableHealthy Volunteers6
1CompletedDiagnosticHeart Diseases1
1CompletedPreventionHigh Blood Pressure (Hypertension)1
1CompletedTreatmentChronic Heart Failure (CHF) / Congestive Heart Failure (CHF)1
1CompletedTreatmentFasting State1
1CompletedTreatmentHealthy Volunteers3
1CompletedTreatmentHigh Blood Pressure (Hypertension)3
1WithdrawnTreatmentPulmonary Hypertension (PH)1
1, 2CompletedTreatmentPre-Hypertension1
1, 2CompletedTreatmentPulmonary Arterial Hypertension (PAH)1
1, 2WithdrawnTreatmentPulmonary Arterial Hypertension (PAH)1
2Active Not RecruitingPreventionCancer, Breast1
2Active Not RecruitingSupportive CareCancer Survivors1
2Active Not RecruitingSupportive CareCancer, Breast / Cardiac Toxicity1
2Active Not RecruitingTreatmentSickle Cell Disorders1
2Active Not RecruitingTreatmentSmoking1
2CompletedTreatmentCocaine Withdrawal / Dependence, Cocaine1
2CompletedTreatmentCocaine-Related Disorders1
2Not Yet RecruitingTreatmentCardiac Transplant1
2Not Yet RecruitingTreatmentHypoglycemia Unawareness1
2RecruitingPreventionCancer Survivors / Heart Failure, Unspecified1
2RecruitingPreventionCardiovascular Abnormalities / HER2 Positive Breast Cancers1
2RecruitingPreventionCardiovascular Disease (CVD) / Diabetes Mellitus (DM) / High Blood Pressure (Hypertension)1
2RecruitingTreatmentProstate Cancer1
2RecruitingTreatmentPulmonary Arterial Hypertension (PAH)1
2TerminatedTreatmentCardiac MRI <40 / Pulmonary Hypertension (PH)1
2TerminatedTreatmentHigh Blood Pressure (Hypertension)1
2Unknown StatusTreatmentPost Traumatic Stress Disorder (PTSD)1
2WithdrawnNot AvailableFeeling Anxious / Relapses / Substance, Addiction1
2, 3Not Yet RecruitingTreatmentGastroesophageal variceal hemorrhage prophylaxis / Liver Cirrhosis / Portal Hypertension1
3CompletedPreventionAtherosclerosis / Cardiovascular Disease (CVD) / Coronary Heart Disease (CHD) / Diabetes Mellitus (DM) / High Blood Pressure (Hypertension) / High Cholesterol / Type 2 Diabetes Mellitus1
3CompletedPreventionAutologous Hematopoietic Stem Cell Transplantation / Leukemia Acute Myeloid Leukemia (AML) / Lymphoid Neoplasms / Malignant Lymphomas / Multiple Myeloma (MM) / Precursor-cell Lymphoblastic Leukemia-Lymphoma1
3CompletedPreventionCancer, Breast / Cardiotoxicity / Heart Failure, Unspecified1
3CompletedPreventionLiver Cirrhosis / Portal Hypertension1
3CompletedTreatmentChronic Heart Failure (CHF)1
3CompletedTreatmentCongestive Heart Failure (CHF)3
3CompletedTreatmentHeart Failure, Unspecified1
3CompletedTreatmentHigh Blood Pressure (Hypertension)1
3CompletedTreatmentHigh Blood Pressure (Hypertension) / Obesity, Abdominal1
3CompletedTreatmentNonvalvular Atrial Fibrillation2
3RecruitingSupportive CareCardiotoxicity / HER2/Neu Positive / Metastatic Malignant Neoplasm in the Brain / Recurrent Breast Carcinoma / Stage IV Breast Cancer AJCC v6 and v71
3RecruitingTreatmentPortal Hypertension1
3TerminatedTreatmentHeart Failure, Unspecified / Nonvalvular Atrial Fibrillation1
3Unknown StatusTreatmentHypertension,Essential1
3WithdrawnTreatmentPortal Hypertension Related to Cirrhosis1
4CompletedBasic ScienceIdiopathic Dilated Cardiomyopathy1
4CompletedDiagnosticDiabetes Mellitus (DM)1
4CompletedDiagnosticHeart Failure, Unspecified / Prophylaxis of cardiomyopathy1
4CompletedPreventionAscites / Hepatic Encephalopathy / Portal Hypertension Gastropathy / Spontaneous Bacterial Peritonitis (SBP) / Varices, Esophageal1
4CompletedPreventionHigh Blood Pressure (Hypertension) / Type 2 Diabetes Mellitus1
4CompletedPreventionVariceal Rebleeding1
4CompletedTreatmentAdverse Effect of Beta-adrenoreceptor Antagonists / Asthma Bronchial / Pulmonary Disease, Chronic Obstructive1
4CompletedTreatmentAltitude / Arterial hypoxia / Heart Failure, Unspecified1
4CompletedTreatmentAlzheimer's Disease (AD)1
4CompletedTreatmentCardiovascular Disease (CVD) / Chronic Kidney Disease (CKD) / Hypertension,Essential / Strokes1
4CompletedTreatmentChronic Heart Failure (CHF)1
4CompletedTreatmentChronic Obstructive Pulmonary Disease (COPD)1
4CompletedTreatmentChronic Stable Angina Pectoris1
4CompletedTreatmentCoronary Artery Disease / High Blood Pressure (Hypertension)1
4CompletedTreatmentHeart Failure, Unspecified / Ventricular Dysfunction, Left1
4CompletedTreatmentHigh Blood Pressure (Hypertension)5
4CompletedTreatmentIntradialytic Hypertension1
4CompletedTreatmentMyocardial Infarction1
4Enrolling by InvitationPreventionLiver Cirrhosis / Portal Hypertension1
4Not Yet RecruitingTreatmentNonvalvular Atrial Fibrillation1
4Not Yet RecruitingTreatmentPortal Hypertension1
4RecruitingBasic ScienceAcute Coronary Syndromes (ACS)1
4RecruitingPreventionEsophageal and Gastric Varices / Hemorrhage / Liver Cirrhosis1
4RecruitingPreventionGastroesophageal Varices / Liver Cirrhosis1
4RecruitingTreatmentCarvedilol / Outflow Tract / Ventricular Premature Complexes1
4RecruitingTreatmentEsophageal and Gastric Varices1
4RecruitingTreatmentEsophageal and Gastric Varices / Liver Cirrhosis1
4RecruitingTreatmentFontan / Univentricular heart1
4RecruitingTreatmentHeart Failure With Reduced Ejection Fraction (HFrEF)1
4RecruitingTreatmentHigh Blood Pressure (Hypertension)1
4RecruitingTreatmentLiver Cirrhosis / Portal Hypertension1
4TerminatedTreatmentHeart Failure, Unspecified1
4Unknown StatusNot AvailableDiabetes Mellitus (DM) / Endothelial Function / High Blood Pressure (Hypertension)1
4Unknown StatusPreventionBecker's Muscular Dystrophy (BMD) / Duchenne's Muscular Dystrophy (DMD)1
4Unknown StatusPreventionDuchenne's Muscular Dystrophy (DMD) / Prophylaxis of cardiomyopathy1
4Unknown StatusPreventionPortal Hypertension1
4Unknown StatusPreventionVariceal Bleeding1
4Unknown StatusTreatmentAnginal Pain / Coronary Heart Disease (CHD) / Hemodialysis Treatment1
4Unknown StatusTreatmentCongestive Cardiomyopathy1
4Unknown StatusTreatmentHigh Blood Pressure (Hypertension)1
4Unknown StatusTreatmentHigh Blood Pressure (Hypertension) / Type 2 Diabetes Mellitus1
4WithdrawnTreatmentChronic Obstructive Pulmonary Disease (COPD) / Heart Failure, Unspecified1
Not AvailableActive Not RecruitingTreatmentHigh Blood Pressure (Hypertension)1
Not AvailableCompletedNot AvailableAcute Myocardial Infarction (AMI) / Heart Failure, Unspecified1
Not AvailableCompletedNot AvailableHealthy Volunteers2
Not AvailableCompletedNot AvailableHigh Blood Pressure (Hypertension)1
Not AvailableCompletedBasic ScienceAmphetamine-Related Disorders / Moods Disorders / Substance-Related Disorders1
Not AvailableCompletedHealth Services ResearchDependence, Cocaine / Opiate Dependence1
Not AvailableCompletedOtherFlu caused by Influenza1
Not AvailableCompletedPreventionDiabetes Mellitus (DM) / High Blood Pressure (Hypertension)1
Not AvailableCompletedPreventionLiver Cirrhosis1
Not AvailableCompletedTreatmentAcute on Chronic Liver Failure1
Not AvailableCompletedTreatmentArrythmias / Nonvalvular Atrial Fibrillation1
Not AvailableCompletedTreatmentChronic Liver Diseases (CLD) / Diastolic Dysfunction1
Not AvailableCompletedTreatmentCirrhosis With Esophageal Varices / Cirrhosis With Large Esophageal Varices1
Not AvailableCompletedTreatmentPulmonary Hypertension (PH)1
Not AvailableNot Yet RecruitingNot AvailableLiver Cirrhosis / Portal Hypertension1
Not AvailableRecruitingNot AvailableLiver Cirrhosis / Portal Hypertension / Varix, Esophageal1
Not AvailableRecruitingPreventionLiver Cirrhosis1
Not AvailableRecruitingPreventionLiver Cirrhosis / Portal Hypertension1
Not AvailableRecruitingTreatmentHeart Failure, Unspecified1
Not AvailableRecruitingTreatmentLiver Cirrhosis1
Not AvailableRecruitingTreatmentNonvalvular Atrial Fibrillation1
Not AvailableUnknown StatusNot AvailableHeart Failure, Unspecified1
Not AvailableUnknown StatusTreatmentChronic Heart Failure (CHF)1
Not AvailableWithdrawnTreatmentHepatocellular Carcinoma With Portal Vein Thrombosis1

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
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/1
Tablet, film coatedOral12.5 mg/301
Tablet, film coatedOral25 mg/1
Tablet, film coatedOral3.125 mg/1
Tablet, film coatedOral6.25 mg/1
Capsule, extended releaseOral10 mg/1
Capsule, extended releaseOral20 mg/1
Capsule, extended releaseOral40 mg/1
Capsule, extended releaseOral80 mg/1
TabletOral50 mg
Kit
TabletOral12.5 mg
TabletOral25 mg
TabletOral3.125 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
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Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7268156Yes2007-09-112023-12-27Us
US8101209Yes2012-01-242026-03-11Us
US6022562Yes2000-02-082016-04-17Us
USRE40000Yes2008-01-082015-12-07Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)114.5 °CPhysProp
water solubilityPractically insoluble (0.583 mg/L)Not Available
logP4.19AVDEEF,A (1997)
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-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0a4i-1662900000-f901a62f255da92e9a09
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0a4i-0220900000-5821022307fc5077033b

Taxonomy

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
Carbazole / Indole / Phenoxy compound / Anisole / Phenol ether / Methoxybenzene / Alkyl aryl ether / Monocyclic benzene moiety / Benzenoid / Pyrrole
show 16 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
secondary alcohol, secondary amino compound, carbazoles (CHEBI:3441)

Targets

Kind
Protein
Organism
Human
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. [PubMed:1712335]
  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. [PubMed:2575762]
  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. [PubMed:2577144]
  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. [PubMed:7908256]
Kind
Protein
Organism
Human
Pharmacological action
Yes
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
ADRA1A
Uniprot ID
P35348
Uniprot Name
Alpha-1A adrenergic receptor
Molecular Weight
51486.005 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. [PubMed:17139284]
  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. [PubMed:17016423]
Kind
Protein
Organism
Human
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. [PubMed:10666308]
Kind
Protein
Organism
Human
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. [PubMed:12360591]
  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. [PubMed:12398570]
  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. [PubMed:14764656]
  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. [PubMed:1712335]
Kind
Protein
Organism
Human
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. [PubMed:11378004]
  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. [PubMed:15071347]
  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. [PubMed:15732037]
  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. [PubMed:15942707]
Kind
Protein
Organism
Human
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. [PubMed:11206715]
  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. [PubMed:11401111]
  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. [PubMed:14692707]
  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. [PubMed:15325927]
  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. [PubMed:15864245]
Kind
Protein
Organism
Human
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. [PubMed:16448880]
  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. [PubMed:16563290]
Kind
Protein
Organism
Human
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. [PubMed:11164846]
  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. [PubMed:16314852]
Kind
Protein
Organism
Human
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. [PubMed:17139284]
  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. [PubMed:17016423]
  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. [PubMed:15374848]
Kind
Protein
Organism
Human
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. [PubMed:15306222]
  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. [PubMed:18657662]
Kind
Protein
Organism
Human
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. [PubMed:15306222]
Kind
Protein
Organism
Human
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. [PubMed:15306222]
Kind
Protein
Organism
Human
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. [PubMed:15306222]
Kind
Protein
Organism
Human
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. [PubMed:15306222]
Kind
Protein
Organism
Human
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. [PubMed:15374848]
Kind
Protein
Organism
Human
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. [PubMed:15732037]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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. [PubMed:21663737]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
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. [PubMed:7909721]
Kind
Protein
Organism
Human
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. [PubMed:25476996]
  2. Laura Dean, MD (2012). Medical Genetics Summaries : Carvedilol Therapy and CYP2D6 Genotype. National Center for Biotechnology Information (US).
  3. Carvedilol FDA [File]
Kind
Protein
Organism
Human
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. [PubMed:19515014]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  3. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
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. 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. [PubMed:19515014]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  3. 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. [PubMed:9280405]
  4. FDA label, Carvedilol [File]
Kind
Protein
Organism
Human
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. 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. [PubMed:19515014]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
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. [PubMed:19515014]
Kind
Protein
Organism
Human
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. 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. [PubMed:19515014]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gas...
Gene Name
PTGS1
Uniprot ID
P23219
Uniprot Name
Prostaglandin G/H synthase 1
Molecular Weight
68685.82 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. [PubMed:19515014]
Kind
Protein
Organism
Human
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. [PubMed:15304429]

Transporters

Kind
Protein
Organism
Human
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. [PubMed:11716514]
  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. [PubMed:11895100]
  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. [PubMed:10571255]
  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. [PubMed:10783826]
  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. [PubMed:12078998]
  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. [PubMed:12708479]
  7. Brodde OE, Kroemer HK: Drug-drug interactions of beta-adrenoceptor blockers. Arzneimittelforschung. 2003;53(12):814-22. [PubMed:14732961]

Drug created on June 13, 2005 07:24 / Updated on November 21, 2018 07:14