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Identification
Name Carvedilol
Accession Number DB01136 (APRD00091)
Type small molecule
Groups approved
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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Carvedilolum [Latin]
Salts Not Available
Brand names
Name Company
Coreg
Coreg CR
Brand mixtures Not Available
Categories
  • Antihypertensive Agents
  • Adrenergic Agents
  • Adrenergic beta-Antagonists
  • Vasodilator Agents
  • Adrenergic alpha-Antagonists
CAS number 72956-09-3
Weight Average: 406.4742
Monoisotopic: 406.18925733
Chemical Formula C24H26N2O4
InChI Key InChIKey=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
Plain Text
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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Carbazoles
Substructures
  • Hydroxy Compounds
  • Indoles and Indole Derivatives
  • Aliphatic and Aryl Amines
  • Phenols and Derivatives
  • Carbazoles
  • Pyrroles
  • Ethers
  • Benzene and Derivatives
  • Amino Alcohols
  • Catechols
  • Heterocyclic compounds
  • Aromatic compounds
  • Anisoles
  • Alcohols and Polyols
  • Phenyl Esters
Pharmacology
Indication For the treatment of mild or moderate (NYHA class II or III) heart failure of ischemic or cardiomyopathic origin.
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.
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
Pathway Name SMPDB ID
Smp00367 Carvedilol Pathway SMP00367
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
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Coreg CR 10 mg 24 Hour Capsule 4.77 USD capsule
Coreg CR 20 mg 24 Hour Capsule 4.77 USD capsule
Coreg CR 40 mg 24 Hour Capsule 4.77 USD capsule
Coreg CR 80 mg 24 Hour Capsule 4.77 USD capsule
Coreg cr 10 mg capsule 4.59 USD capsule
Coreg cr 20 mg capsule 4.59 USD capsule
Coreg cr 40 mg capsule 4.59 USD capsule
Coreg cr 80 mg capsule 4.59 USD capsule
Coreg 12.5 mg tablet 2.54 USD tablet
Coreg 25 mg tablet 2.54 USD tablet
Coreg 3.125 mg tablet 2.54 USD tablet
Coreg 6.25 mg tablet 2.54 USD tablet
Carvedilol 12.5 mg tablet 2.18 USD tablet
Carvedilol 25 mg tablet 2.18 USD tablet
Carvedilol 3.125 mg tablet 2.18 USD tablet
Carvedilol 6.25 mg tablet 2.18 USD tablet
Apo-Carvedilol 12.5 mg Tablet 0.84 USD tablet
Apo-Carvedilol 25 mg Tablet 0.84 USD tablet
Apo-Carvedilol 3.125 mg Tablet 0.84 USD tablet
Apo-Carvedilol 6.25 mg Tablet 0.84 USD tablet
Phl-Carvedilol 12.5 mg Tablet 0.79 USD tablet
Phl-Carvedilol 3.125 mg Tablet 0.79 USD tablet
Phl-Carvedilol 6.25 mg Tablet 0.79 USD tablet
Pms-Carvedilol 12.5 mg Tablet 0.79 USD tablet
Pms-Carvedilol 25 mg Tablet 0.79 USD tablet
Pms-Carvedilol 3.125 mg Tablet 0.79 USD tablet
Pms-Carvedilol 6.25 mg Tablet 0.79 USD tablet
Ran-Carvedilol 12.5 mg Tablet 0.79 USD tablet
Ran-Carvedilol 25 mg Tablet 0.79 USD tablet
Ran-Carvedilol 3.125 mg Tablet 0.79 USD tablet
Ran-Carvedilol 6.25 mg Tablet 0.79 USD tablet
Ratio-Carvedilol 12.5 mg Tablet 0.79 USD tablet
Ratio-Carvedilol 25 mg Tablet 0.79 USD tablet
Ratio-Carvedilol 3.125 mg Tablet 0.79 USD tablet
Ratio-Carvedilol 6.25 mg Tablet 0.79 USD tablet
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Patents
Country Patent Number Approved Expires (estimated)
United States 7268156 2003-12-27 2023-12-27
United States RE40000 1995-06-07 2015-06-07
Properties
State solid
Experimental Properties
Property Value Source
melting point 114.5 °C PhysProp
water solubility Practically insoluble (0.583 mg/L) Not Available
logP 4.19 AVDEEF,A (1997)
Predicted Properties
Property Value Source
water solubility 4.44e-03 g/l ALOGPS
logP 3.05 ALOGPS
logP 3.42 ChemAxon
logS -5 ALOGPS
pKa (strongest acidic) 14.03 ChemAxon
pKa (strongest basic) 8.74 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 5 ChemAxon
hydrogen donor count 3 ChemAxon
polar surface area 75.74 ChemAxon
rotatable bond count 10 ChemAxon
refractivity 115.64 ChemAxon
polarizability 45.03 ChemAxon
References
Synthesis Reference Not Available
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
Resource Link
KEGG Drug D00255 Link_out
KEGG Compound C06875 Link_out
PubChem Compound 2585 Link_out
PubChem Substance 46505146 Link_out
ChemSpider 2487 Link_out
BindingDB 25759 Link_out
ChEBI 3441 Link_out
ChEMBL 3441 Link_out
Therapeutic Targets Database DAP000135 Link_out
PharmGKB PA448817 Link_out
IUPHAR 551 Link_out
Guide to Pharmacology 551 Link_out
Drug Product Database 2252317 Link_out
RxList http://www.rxlist.com/cgi/generic3/carvedilol.htm Link_out
Drugs.com http://www.drugs.com/cdi/carvedilol.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Carvedilol Link_out
ATC Codes
  • C07AG02
AHFS Codes
  • 24:04.00
  • 24:24.00
PDB Entries Not Available
FDA label show (1.25 MB)
MSDS show (32.9 KB)
Interactions
Drug Interactions
Drug Interaction
Acetohexamide The beta-blocker, carvedilol, may decrease symptoms of hypoglycemia.
Chlorpropamide The beta-blocker, carvedilol, may decrease symptoms of hypoglycemia.
Citalopram The SSRI, citalopram, may increase the bradycardic effect of the beta-blocker, carvedilol.
Clonidine Increased hypertension when clonidine stopped
Cyclosporine Carvedilol may increase the therapeutic and adverse effects of cyclosporine.
Digoxin Carvedilol may increase the serum levels and effect of digoxin.
Dihydroergotamine Ischemia with risk of gangrene
Dihydroergotoxine Ischemia with risk of gangrene
Disopyramide The beta-blocker, carvedilol, may increase the toxicity of disopyramide.
Epinephrine Hypertension, then bradycardia
Ergonovine Ischemia with risk of gangrene
Ergotamine Ischemia with risk of gangrene
Escitalopram The SSRI, escitalopram, may increase the bradycardic effect of the beta-blocker, carvedilol.
Fenoterol Antagonism
Fluoxetine The SSRI, fluoxetine, may increase the bradycardic effect of the beta-blocker, carvedilol.
Formoterol Antagonism
Gliclazide The beta-blocker, carvedilol, may decrease symptoms of hypoglycemia.
Glipizide The beta-blocker, carvedilol, may decrease symptoms of hypoglycemia.
Glisoxepide The beta-blocker, carvedilol, may decrease symptoms of hypoglycemia.
Glyburide The beta-blocker, carvedilol, may decrease symptoms of hypoglycemia.
Glycodiazine The beta-blocker, carvedilol, may decrease symptoms of hypoglycemia.
Ibuprofen Risk of inhibition of renal prostaglandins
Indomethacin Risk of inhibition of renal prostaglandins
Insulin The beta-blocker, carvedilol, may decrease symptoms of hypoglycemia.
Insulin Aspart The beta-blocker, carvedilol, may decrease symptoms of hypoglycemia.
Insulin Detemir The beta-blocker, carvedilol, may decrease symptoms of hypoglycemia.
Insulin Glargine The beta-blocker, carvedilol, may decrease symptoms of hypoglycemia.
Insulin Glulisine The beta-blocker, carvedilol, may decrease symptoms of hypoglycemia.
Insulin Lispro The beta-blocker, carvedilol, may decrease symptoms of hypoglycemia.
Isoproterenol Antagonism
Lidocaine The beta-blocker, carvedilol, may increase the effect and toxicity of lidocaine.
Methysergide Ischemia with risk of gangrene
Orciprenaline Antagonism
Paroxetine The SSRI, paroxetine, may increase the bradycardic effect of the beta-blocker, carvedilol.
Pipobroman Antagonism
Pirbuterol Antagonism
Piroxicam Risk of inhibition of renal prostaglandins
Prazosin Risk of hypotension at the beginning of therapy
Procaterol Antagonism
Repaglinide The beta-blocker, carvedilol, may decrease symptoms of hypoglycemia.
Salbutamol Antagonism
Salmeterol Antagonism
Sertraline The SSRI, sertraline, may increase the bradycardic effect of the beta-blocker, carvedilol.
Terazosin Increased risk of hypotension. Initiate concomitant therapy cautiously.
Terbinafine Terbinafine 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.
Terbutaline Antagonism
Tolazamide The beta-blocker, carvedilol, may decrease symptoms of hypoglycemia.
Tolbutamide The beta-blocker, carvedilol, may decrease symptoms of hypoglycemia.
Topotecan The 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.
Treprostinil Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
Verapamil Increased 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

Pharmacological action: yes
Actions: antagonist

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 equal affinity

Organism class: human
UniProt ID: P08588 Link_out
Gene: ADRB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: antagonist

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) proteins

Organism class: human
UniProt ID: P35348 Link_out
Gene: ADRA1A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown
Actions: inhibitor

Transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone

Organism class: human
UniProt ID: O95298 Link_out
Gene: NDUFC2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown
Actions: antagonist

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 30-fold greater affinity than it does norepinephrine

Organism class: human
UniProt ID: P07550 Link_out
Gene: ADRB2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown
Actions: other

Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis, and induces permeabilization of blood vessels. Binds to the VEGFR1/Flt-1 and VEGFR2/Kdr receptors, heparan sulfate and heparin. Neuropilin-1 binds isoforms VEGF-165 and VEGF-145

Organism class: human
UniProt ID: P15692 Link_out
Gene: VEGF Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown
Actions: other

Acts as a cardiac hormone with a variety of biological actions including natriuresis, diuresis, vasorelaxation, and inhibition of renin and aldosterone secretion. It is thought to play a key role in cardiovascular homeostasis. Helps restore the body's salt and water balance. Improves heart function

Organism class: human
UniProt ID: P16860 Link_out
Gene: NPPB Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown
Actions: other

One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell. May play a critical role in the physiology of hearing by participating in the recycling of potassium to the cochlear endolymph

Organism class: human
UniProt ID: P17302 Link_out
Gene: GJA1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown
Actions: inhibitor

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 delayed rectifying potassium current in heart (IKr). Isoform 3 has no channel activity by itself, but modulates channel characteristics when associated with isoform 1

Organism class: human
UniProt ID: Q12809 Link_out
Gene: KCNH2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown
Actions: inhibitor

Important in cell-cell recognition. Appears to function in leukocyte-endothelial cell adhesion. Interacts with the beta-1 integrin VLA4 on leukocytes, and mediates both adhesion and signal transduction. The VCAM1/VLA4 interaction may play a pathophysiologic role both in immune responses and in leukocyte emigration to sites of inflammation

Organism class: human
UniProt ID: P19320 Link_out
Gene: VCAM1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Enzymes

1. Xanthine dehydrogenase/oxidase

This enzyme can be converted from the dehydrogenase form (D) to the oxidase form (O) irreversibly by proteolysis or reversibly through the oxidation of sulfhydryl groups

UniProt ID: P47989 Link_out
Gene: XDH Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate

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 unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate

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 antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate

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 unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

UniProt ID: P05177 Link_out
Gene: CYP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate

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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate

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 unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P04798 Link_out
Gene: CYP1A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate

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 or carcinogenic forms

UniProt ID: P05181 Link_out
Gene: CYP2E1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate

May play an important role in regulating or promoting cell proliferation in some normal and neoplastically transformed cells

UniProt ID: P23219 Link_out
Gene: PTGS1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: inhibitor

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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 February 08, 2013 16:19