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Identification
NameCarvedilol
Accession NumberDB01136  (APRD00091)
Typesmall molecule
Groupsapproved, 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
SynonymLanguageCode
CarvedilolumLatinINN
SaltsNot Available
Brand names
NameCompany
CoregNot Available
Coreg CRNot Available
Brand mixturesNot Available
Categories
CAS number72956-09-3
WeightAverage: 406.4742
Monoisotopic: 406.18925733
Chemical FormulaC24H26N2O4
InChI KeyInChIKey=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
[3-(9H-carbazol-4-yloxy)-2-hydroxypropyl][2-(2-methoxyphenoxy)ethyl]amine
SMILES
COC1=CC=CC=C1OCCNCC(O)COC1=CC=CC2=C1C1=CC=CC=C1N2
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassIndoles and Derivatives
SubclassCarbazoles
Direct parentCarbazoles
Alternative parentsIndoles; Anisoles; Alkyl Aryl Ethers; Pyrroles; Secondary Alcohols; 1,2-Aminoalcohols; Polyols; Polyamines; Dialkylamines
Substituentsindole; phenol ether; anisole; alkyl aryl ether; benzene; pyrrole; 1,2-aminoalcohol; polyol; secondary alcohol; secondary amine; polyamine; secondary aliphatic amine; ether; amine; alcohol; organonitrogen compound
Classification descriptionThis compound belongs to the carbazoles. These are compounds containing a three ring system containing a pyrrole ring fused on either side to a benzene ring.
Pharmacology
IndicationFor the treatment of mild or moderate (NYHA class II or III) heart failure of ischemic or cardiomyopathic origin.
PharmacodynamicsCarvedilol 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 actionCarvedilol 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.
AbsorptionCarvedilol 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 binding98%
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.

SubstrateEnzymesProduct
Carvedilol
8-HydroxycarvedilolDetails
Carvedilol
4'-HydroxycarvedilolDetails
Carvedilol
5'-HydroxycarvedilolDetails
Carvedilol
O-DesmethylcarvedilolDetails
Carvedilol
1-HydroxycarvedilolDetails
Carvedilol
    4'-hydroxyphenyl CarvedilolDetails
    Route of eliminationCarvedilol 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 life7-10 hours
    Clearance
    • 500-700 mL/min
    ToxicityNot expected to be toxic following ingestion.
    Affected organisms
    • Humans and other mammals
    Pathways
    PathwayCategorySMPDB ID
    Carvedilol Action PathwayDrug actionSMP00367
    SNP Mediated Effects
    Interacting Gene/EnzymeSNP RS IDAllele nameDefining changeEffectReference(s)
    Beta-1 adrenergic receptor
    Gene symbol: ADRB1
    UniProt: P08588
    rs1801253 Not AvailableC AlleleImproved response to blood pressure medication12844134
    Beta-1 adrenergic receptor
    Gene symbol: ADRB1
    UniProt: P08588
    rs1801252 Not AvailableA AlleleImproved response to blood pressure medication12844134
    Beta-1 adrenergic receptor
    Gene symbol: ADRB1
    UniProt: P08588
    rs1801253 Not AvailableG > CBetter response to drug therapy22192668
    SNP Mediated Adverse Drug ReactionsNot Available
    ADMET
    Predicted ADMET features
    Property Value Probability
    Human Intestinal Absorption + 0.9706
    Blood Brain Barrier - 0.6814
    Caco-2 permeable - 0.6308
    P-glycoprotein substrate Substrate 0.8552
    P-glycoprotein inhibitor I Non-inhibitor 0.8729
    P-glycoprotein inhibitor II Non-inhibitor 0.6521
    Renal organic cation transporter Non-inhibitor 0.5405
    CYP450 2C9 substrate Non-substrate 0.7517
    CYP450 2D6 substrate Substrate 0.8918
    CYP450 3A4 substrate Substrate 0.5408
    CYP450 1A2 substrate Inhibitor 0.524
    CYP450 2C9 substrate Non-inhibitor 0.8496
    CYP450 2D6 substrate Non-inhibitor 0.7274
    CYP450 2C19 substrate Non-inhibitor 0.5676
    CYP450 3A4 substrate Non-inhibitor 0.6352
    CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.6048
    Ames test Non AMES toxic 0.8261
    Carcinogenicity Non-carcinogens 0.9692
    Biodegradation Not ready biodegradable 0.963
    Rat acute toxicity 2.4566 LD50, mol/kg Not applicable
    hERG inhibition (predictor I) Weak inhibitor 0.5725
    hERG inhibition (predictor II) Inhibitor 0.8889
    Pharmacoeconomics
    Manufacturers
    • Actavis elizabeth llc
    • Apotex inc etobicoke site
    • Aurobindo pharma ltd
    • Caraco pharmaceutical laboratories ltd
    • Dr reddys laboratories ltd
    • Glenmark generics ltd
    • Hikma pharmaceuticals
    • Lupin ltd
    • Mylan pharmaceuticals inc
    • Pliva hrvatska doo
    • Ranbaxy laboratories ltd
    • Sandoz inc
    • Taro pharmaceutical industries ltd
    • Teva pharmaceuticals usa inc
    • Watson laboratories
    • Wockhardt ltd
    • Zydus pharmaceuticals usa inc
    • Smithkline beecham corp dba glaxosmithkline
    • Sb pharmco puerto rico inc
    Packagers
    Dosage forms
    FormRouteStrength
    TabletOral
    Prices
    Unit descriptionCostUnit
    Coreg CR 10 mg 24 Hour Capsule4.77USDcapsule
    Coreg CR 20 mg 24 Hour Capsule4.77USDcapsule
    Coreg CR 40 mg 24 Hour Capsule4.77USDcapsule
    Coreg CR 80 mg 24 Hour Capsule4.77USDcapsule
    Coreg cr 10 mg capsule4.59USDcapsule
    Coreg cr 20 mg capsule4.59USDcapsule
    Coreg cr 40 mg capsule4.59USDcapsule
    Coreg cr 80 mg capsule4.59USDcapsule
    Coreg 12.5 mg tablet2.54USDtablet
    Coreg 25 mg tablet2.54USDtablet
    Coreg 3.125 mg tablet2.54USDtablet
    Coreg 6.25 mg tablet2.54USDtablet
    Carvedilol 12.5 mg tablet2.18USDtablet
    Carvedilol 25 mg tablet2.18USDtablet
    Carvedilol 3.125 mg tablet2.18USDtablet
    Carvedilol 6.25 mg tablet2.18USDtablet
    Apo-Carvedilol 12.5 mg Tablet0.84USDtablet
    Apo-Carvedilol 25 mg Tablet0.84USDtablet
    Apo-Carvedilol 3.125 mg Tablet0.84USDtablet
    Apo-Carvedilol 6.25 mg Tablet0.84USDtablet
    Phl-Carvedilol 12.5 mg Tablet0.79USDtablet
    Phl-Carvedilol 3.125 mg Tablet0.79USDtablet
    Phl-Carvedilol 6.25 mg Tablet0.79USDtablet
    Pms-Carvedilol 12.5 mg Tablet0.79USDtablet
    Pms-Carvedilol 25 mg Tablet0.79USDtablet
    Pms-Carvedilol 3.125 mg Tablet0.79USDtablet
    Pms-Carvedilol 6.25 mg Tablet0.79USDtablet
    Ran-Carvedilol 12.5 mg Tablet0.79USDtablet
    Ran-Carvedilol 25 mg Tablet0.79USDtablet
    Ran-Carvedilol 3.125 mg Tablet0.79USDtablet
    Ran-Carvedilol 6.25 mg Tablet0.79USDtablet
    Ratio-Carvedilol 12.5 mg Tablet0.79USDtablet
    Ratio-Carvedilol 25 mg Tablet0.79USDtablet
    Ratio-Carvedilol 3.125 mg Tablet0.79USDtablet
    Ratio-Carvedilol 6.25 mg Tablet0.79USDtablet
    DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
    Patents
    CountryPatent NumberApprovedExpires (estimated)
    United States72681562003-12-272023-12-27
    United StatesRE400001995-06-072015-06-07
    Properties
    Statesolid
    Experimental Properties
    PropertyValueSource
    melting point114.5 °CPhysProp
    water solubilityPractically insoluble (0.583 mg/L)Not Available
    logP4.19AVDEEF,A (1997)
    Predicted Properties
    PropertyValueSource
    water solubility4.44e-03 g/lALOGPS
    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 area75.74ChemAxon
    rotatable bond count10ChemAxon
    refractivity115.64ChemAxon
    polarizability45.03ChemAxon
    number of rings4ChemAxon
    bioavailability1ChemAxon
    rule of fiveYesChemAxon
    Ghose filterYesChemAxon
    Veber's ruleNoChemAxon
    MDDR-like ruleYesChemAxon
    Spectra
    SpectraNot Available
    References
    Synthesis Reference

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

    US20030166702
    General Reference
    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
    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
    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
    External Links
    ResourceLink
    KEGG DrugD00255
    KEGG CompoundC06875
    PubChem Compound2585
    PubChem Substance46505146
    ChemSpider2487
    BindingDB25759
    ChEBI3441
    ChEMBLCHEMBL723
    Therapeutic Targets DatabaseDAP000135
    PharmGKBPA448817
    IUPHAR551
    Guide to Pharmacology551
    Drug Product Database2252317
    RxListhttp://www.rxlist.com/cgi/generic3/carvedilol.htm
    Drugs.comhttp://www.drugs.com/cdi/carvedilol.html
    WikipediaCarvedilol
    ATC CodesC07AG02
    AHFS Codes
    • 24:04.00
    • 24:24.00
    PDB EntriesNot Available
    FDA labelshow(1.25 MB)
    MSDSshow(32.9 KB)
    Interactions
    Drug Interactions
    Drug
    AcetohexamideThe beta-blocker, carvedilol, may decrease symptoms of hypoglycemia.
    ChlorpropamideThe beta-blocker, carvedilol, may decrease symptoms of hypoglycemia.
    CitalopramThe SSRI, citalopram, may increase the bradycardic effect of the beta-blocker, carvedilol.
    ClonidineIncreased hypertension when clonidine stopped
    CyclosporineCarvedilol may increase the therapeutic and adverse effects of cyclosporine.
    DigoxinCarvedilol may increase the serum levels and effect of digoxin.
    DihydroergotamineIschemia with risk of gangrene
    DisopyramideThe beta-blocker, carvedilol, may increase the toxicity of disopyramide.
    EpinephrineHypertension, then bradycardia
    ErgonovineIschemia with risk of gangrene
    ErgotamineIschemia with risk of gangrene
    EscitalopramThe SSRI, escitalopram, may increase the bradycardic effect of the beta-blocker, carvedilol.
    EtravirineCarvedilol, when used concomitantly with etravirine (a CYP2C9 inhibitor), may experience an increase in serum concentration. It is recommended to monitor for signs and symptoms of an increased response to carvedilol, such as orthostatic hypotension and bradycardia.
    FenoterolAntagonism
    FluoxetineThe SSRI, fluoxetine, may increase the bradycardic effect of the beta-blocker, carvedilol.
    FormoterolAntagonism
    GliclazideThe beta-blocker, carvedilol, may decrease symptoms of hypoglycemia.
    GlipizideThe beta-blocker, carvedilol, may decrease symptoms of hypoglycemia.
    GlisoxepideThe beta-blocker, carvedilol, may decrease symptoms of hypoglycemia.
    GlyburideThe beta-blocker, carvedilol, may decrease symptoms of hypoglycemia.
    GlycodiazineThe beta-blocker, carvedilol, may decrease symptoms of hypoglycemia.
    IbuprofenRisk of inhibition of renal prostaglandins
    IndomethacinRisk of inhibition of renal prostaglandins
    Insulin AspartThe beta-blocker, carvedilol, may decrease symptoms of hypoglycemia.
    Insulin DetemirThe beta-blocker, carvedilol, may decrease symptoms of hypoglycemia.
    Insulin GlargineThe beta-blocker, carvedilol, may decrease symptoms of hypoglycemia.
    Insulin GlulisineThe beta-blocker, carvedilol, may decrease symptoms of hypoglycemia.
    Insulin LisproThe beta-blocker, carvedilol, may decrease symptoms of hypoglycemia.
    IsoprenalineAntagonism
    LidocaineThe beta-blocker, carvedilol, may increase the effect and toxicity of lidocaine.
    MethysergideIschemia with risk of gangrene
    OrciprenalineAntagonism
    ParoxetineThe SSRI, paroxetine, may increase the bradycardic effect of the beta-blocker, carvedilol.
    PipobromanAntagonism
    PirbuterolAntagonism
    PiroxicamRisk of inhibition of renal prostaglandins
    PrazosinRisk of hypotension at the beginning of therapy
    ProcaterolAntagonism
    RepaglinideThe beta-blocker, carvedilol, may decrease symptoms of hypoglycemia.
    SalbutamolAntagonism
    SalmeterolAntagonism
    SertralineThe SSRI, sertraline, may increase the bradycardic effect of the beta-blocker, carvedilol.
    TerazosinIncreased risk of hypotension. Initiate concomitant therapy cautiously.
    TerbinafineTerbinafine may reduce the metabolism and clearance of Carvedilol. Consider alternate therapy or monitor for therapeutic/adverse effects of Carvedilol if Terbinafine is initiated, discontinued or dose changed.
    TerbutalineAntagonism
    TolazamideThe beta-blocker, carvedilol, may decrease symptoms of hypoglycemia.
    TolbutamideThe beta-blocker, carvedilol, may decrease symptoms of hypoglycemia.
    TopotecanThe p-glycoprotein inhibitor, Carvedilol, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
    TreprostinilAdditive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
    VerapamilIncreased effect of both drugs
    Food Interactions
    • Take with food, food slows the absorption rate and reduces the incidence of adverse effects (extent of absorption is not affected).

    1. Beta-1 adrenergic receptor

    Kind: protein

    Organism: Human

    Pharmacological action: yes

    Actions: antagonist

    Components

    Name UniProt ID Details
    Beta-1 adrenergic receptor P08588 Details

    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
    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
    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
    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

    2. Alpha-1A adrenergic receptor

    Kind: protein

    Organism: Human

    Pharmacological action: yes

    Actions: antagonist

    Components

    Name UniProt ID Details
    Alpha-1A adrenergic receptor P35348 Details

    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
    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

    3. NADH dehydrogenase [ubiquinone] 1 subunit C2

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: inhibitor

    Components

    Name UniProt ID Details
    NADH dehydrogenase [ubiquinone] 1 subunit C2 O95298 Details

    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

    4. Beta-2 adrenergic receptor

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: antagonist

    Components

    Name UniProt ID Details
    Beta-2 adrenergic receptor P07550 Details

    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
    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
    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
    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

    5. Vascular endothelial growth factor A

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: other

    Components

    Name UniProt ID Details
    Vascular endothelial growth factor A P15692 Details

    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
    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
    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
    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

    6. Natriuretic peptides B

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: other

    Components

    Name UniProt ID Details
    Natriuretic peptides B P16860 Details

    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
    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
    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
    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
    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

    7. Gap junction alpha-1 protein

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: other

    Components

    Name UniProt ID Details
    Gap junction alpha-1 protein P17302 Details

    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
    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

    8. Potassium voltage-gated channel subfamily H member 2

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: inhibitor

    Components

    Name UniProt ID Details
    Potassium voltage-gated channel subfamily H member 2 Q12809 Details

    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
    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

    9. Vascular cell adhesion protein 1

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: inhibitor

    Components

    Name UniProt ID Details
    Vascular cell adhesion protein 1 P19320 Details

    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
    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
    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

    1. Xanthine dehydrogenase/oxidase

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Components

    Name UniProt ID Details
    Xanthine dehydrogenase/oxidase P47989 Details

    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

    2. Cytochrome P450 2C9

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: substrate

    Components

    Name UniProt ID Details
    Cytochrome P450 2C9 P11712 Details

    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
    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. Epub 2009 Nov 24. Pubmed

    3. Cytochrome P450 2D6

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: substrate

    Components

    Name UniProt ID Details
    Cytochrome P450 2D6 P10635 Details

    References:

    1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
    2. 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
    3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

    4. Cytochrome P450 1A2

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: substrate

    Components

    Name UniProt ID Details
    Cytochrome P450 1A2 P05177 Details

    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
    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. Epub 2009 Nov 24. Pubmed

    5. Cytochrome P450 3A4

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: substrate

    Components

    Name UniProt ID Details
    Cytochrome P450 3A4 P08684 Details

    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
    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. Epub 2009 Nov 24. Pubmed

    6. Cytochrome P450 1A1

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: substrate

    Components

    Name UniProt ID Details
    Cytochrome P450 1A1 P04798 Details

    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

    7. Cytochrome P450 2E1

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: substrate

    Components

    Name UniProt ID Details
    Cytochrome P450 2E1 P05181 Details

    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
    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. Epub 2009 Nov 24. Pubmed

    8. Prostaglandin G/H synthase 1

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: substrate

    Components

    Name UniProt ID Details
    Prostaglandin G/H synthase 1 P23219 Details

    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

    1. Multidrug resistance protein 1

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: inhibitor

    Components

    Name UniProt ID Details
    Multidrug resistance protein 1 P08183 Details

    References:

    1. Wang EJ, Casciano CN, Clement RP, Johnson WW: Active transport of fluorescent P-glycoprotein substrates: evaluation as markers and interaction with inhibitors. Biochem Biophys Res Commun. 2001 Nov 30;289(2):580-5. Pubmed
    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
    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
    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
    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
    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
    7. Brodde OE, Kroemer HK: Drug-drug interactions of beta-adrenoceptor blockers. Arzneimittelforschung. 2003;53(12):814-22. Pubmed

    Comments
    Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:13