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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
(+-)-1-(Carbazol-4-yloxy)-3-((2-(O-methoxyphenoxy)ethyl)amino)-2-propanolNot AvailableNot Available
CarvedilolNot AvailableNot Available
CarvedilolumLatinINN
SKF 105517Not AvailableNot Available
SaltsNot Available
Brand names
NameCompany
CoregNot Available
Coreg CRNot Available
COREGCRNot Available
Brand mixturesNot Available
Categories
CAS number72956-09-3
WeightAverage: 406.4742
Monoisotopic: 406.18925733
Chemical FormulaC24H26N2O4
InChI KeyOGHNVEJMJSYVRP-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
Not Available
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 Solubility0.00444ALOGPS
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
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).

Targets

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

10. Alpha-1D adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Alpha-1D adrenergic receptor P25100 Details

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
  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

11. Alpha-1B adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Alpha-1B adrenergic receptor P35368 Details

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

12. Alpha-2C adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Alpha-2C adrenergic receptor P18825 Details

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

13. Alpha-2B adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Alpha-2B adrenergic receptor P18089 Details

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

14. Alpha-2A adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Alpha-2A adrenergic receptor P08913 Details

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

15. E-selectin

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
E-selectin P16581 Details

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

16. Hypoxia-inducible factor 1-alpha

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: modulator

Components

Name UniProt ID Details
Hypoxia-inducible factor 1-alpha Q16665 Details

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

Enzymes

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

Transporters

1. Multidrug resistance protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

References:

  1. Wang EJ, Casciano CN, Clement RP, Johnson WW: Active transport of fluorescent P-glycoprotein substrates: evaluation as markers and interaction with inhibitors. Biochem Biophys Res Commun. 2001 Nov 30;289(2):580-5. Pubmed
  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

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