Details
| Stereochemistry | RACEMIC |
| Molecular Formula | C24H26N2O4.ClH |
| Molecular Weight | 442.935 |
| Optical Activity | ( + / - ) |
| Defined Stereocenters | 0 / 1 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
Cl.COC1=C(OCCNCC(O)COC2=CC=CC3=C2C4=C(N3)C=CC=C4)C=CC=C1
InChI
InChIKey=OSZYHTJPTLLICF-UHFFFAOYSA-N
InChI=1S/C24H26N2O4.ClH/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;1H
| Molecular Formula | C24H26N2O4 |
| Molecular Weight | 406.4742 |
| Charge | 0 |
| Count |
|
| Stereochemistry | RACEMIC |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 1 |
| E/Z Centers | 0 |
| Optical Activity | ( + / - ) |
| Molecular Formula | ClH |
| Molecular Weight | 36.461 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
Carvedilol competitively blocks β1, β2 and α1 receptors. The drug lacks sympathomimetic activity and has vasodilating properties that are exerted primarily through α1-blockade. Animal models indicate that carvedilol confers protection against myocardial necrosis, arrhythmia and cell damage caused by oxidising free radicals, and the drug has no adverse effects on plasma lipid profiles. COREG® (carvedilol) is a racemic mixture in which nonselective β-adrenoreceptor blocking activity is present in the S(-) enantiomer and α1-adrenergic blocking activity is present in both R(+) and S(-) enantiomers at equal potency. Carvedilol is the first drug of its kind to be approved for the treatment of congestive heart failure, and is now the standard of care for this devastating disease. Carvedilol is also confirmed as effective in the management of mild to moderate hypertension and ischaemic heart disease.
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL2094118 |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | COREG Approved UseCOREG® (carvedilol) is indicated for the treatment of mild-to-severe chronic heart failure of ischemic or cardiomyopathic origin, usually in addition to diuretics, ACE inhibitors, and digitalis, to increase survival and, also, to reduce the risk of hospitalization.
COREG is indicated to reduce cardiovascular mortality in clinically stable patients who
have survived the acute phase of a myocardial infarction and have a left ventricular ejection fraction of ≤40% (with or without symptomatic heart failure).
COREG is indicated for the management of essential hypertension. It can be used alone or in combination with other antihypertensive agents, especially thiazide-type diuretics. Launch Date8.1103677E11 |
|||
| Primary | COREG Approved UseCOREG® (carvedilol) is indicated for the treatment of mild-to-severe chronic heart failure of ischemic or cardiomyopathic origin, usually in addition to diuretics, ACE inhibitors, and digitalis, to increase survival and, also, to reduce the risk of hospitalization.
COREG is indicated to reduce cardiovascular mortality in clinically stable patients who
have survived the acute phase of a myocardial infarction and have a left ventricular ejection fraction of ≤40% (with or without symptomatic heart failure).
COREG is indicated for the management of essential hypertension. It can be used alone or in combination with other antihypertensive agents, especially thiazide-type diuretics. Launch Date8.1103677E11 |
|||
| Primary | COREG Approved UseCOREG® (carvedilol) is indicated for the treatment of mild-to-severe chronic heart failure of ischemic or cardiomyopathic origin, usually in addition to diuretics, ACE inhibitors, and digitalis, to increase survival and, also, to reduce the risk of hospitalization.
COREG is indicated to reduce cardiovascular mortality in clinically stable patients who
have survived the acute phase of a myocardial infarction and have a left ventricular ejection fraction of ≤40% (with or without symptomatic heart failure).
COREG is indicated for the management of essential hypertension. It can be used alone or in combination with other antihypertensive agents, especially thiazide-type diuretics. Launch Date8.1103677E11 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
18.4 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10934668 |
6.25 mg 2 times / day steady-state, oral dose: 6.25 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
CARVEDILOL, (+)- plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED |
|
8.46 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10934668 |
6.25 mg 2 times / day steady-state, oral dose: 6.25 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
CARVEDILOL, (-)- plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED |
|
26.5 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10934668 |
6.25 mg 2 times / day steady-state, oral dose: 6.25 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
CARVEDILOL plasma | Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
94.3 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10934668 |
6.25 mg 2 times / day steady-state, oral dose: 6.25 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
CARVEDILOL, (+)- plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED |
|
42.2 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10934668 |
6.25 mg 2 times / day steady-state, oral dose: 6.25 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
CARVEDILOL, (-)- plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED |
|
139 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10934668 |
6.25 mg 2 times / day steady-state, oral dose: 6.25 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
CARVEDILOL plasma | Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
| Dose | Population | Adverse events |
|---|---|---|
300 mg single, oral Overdose Dose: 300 mg Route: oral Route: single Dose: 300 mg Co-administed with:: lorazepam(7 mg) Sources: |
unknown, 41 years n = 1 Health Status: unknown Age Group: 41 years Sex: M Population Size: 1 Sources: |
Other AEs: Wheezing... |
80 mg 1 times / day multiple, oral Highest studied dose Dose: 80 mg, 1 times / day Route: oral Route: multiple Dose: 80 mg, 1 times / day Sources: |
unhealthy, 66.7±12.0 years n = 7 Health Status: unhealthy Condition: chronic heart failure Age Group: 66.7±12.0 years Sex: M+F Population Size: 7 Sources: |
|
375 mg single, oral Overdose Dose: 375 mg Route: oral Route: single Dose: 375 mg Co-administed with:: simvastatin(fifteen 20-mg tablets) Sources: |
unhealthy, 84 years n = 1 Health Status: unhealthy Age Group: 84 years Sex: M Population Size: 1 Sources: |
Other AEs: Hypotension... |
50 mg 1 times / day steady, oral Recommended Dose: 50 mg, 1 times / day Route: oral Route: steady Dose: 50 mg, 1 times / day Sources: |
unhealthy, adult n = 765 Health Status: unhealthy Condition: heart failure Age Group: adult Population Size: 765 Sources: |
Disc. AE: Hypotension... AEs leading to discontinuation/dose reduction: Hypotension (0.7%) Sources: |
20 mg 2 times / day multiple, oral Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: Page: p. 61 |
unhealthy, adult n = 54 Health Status: unhealthy Age Group: adult Population Size: 54 Sources: Page: p. 61 |
Disc. AE: Congestive cardiac failure... AEs leading to discontinuation/dose reduction: Congestive cardiac failure (moderate, 1 patient) Sources: Page: p. 61 |
25 mg 2 times / day steady, oral Dose: 25 mg, 2 times / day Route: oral Route: steady Dose: 25 mg, 2 times / day Sources: |
unhealthy, adult n = 1156 Health Status: unhealthy Condition: severe heart failure Age Group: adult Population Size: 1156 Sources: |
Disc. AE: Dizziness... AEs leading to discontinuation/dose reduction: Dizziness (1.3%) Sources: |
6.25 mg 2 times / day multiple, oral Dose: 6.25 mg, 2 times / day Route: oral Route: multiple Dose: 6.25 mg, 2 times / day Sources: Page: p. 61 |
unhealthy, adult n = 54 Health Status: unhealthy Age Group: adult Population Size: 54 Sources: Page: p. 61 |
Disc. AE: Abdominal distension... AEs leading to discontinuation/dose reduction: Abdominal distension (1 patient) Sources: Page: p. 61 |
6.25 mg 2 times / day multiple, oral Dose: 6.25 mg, 2 times / day Route: oral Route: multiple Dose: 6.25 mg, 2 times / day Sources: Page: p. 61 |
unhealthy, adult n = 54 Health Status: unhealthy Age Group: adult Population Size: 54 Sources: Page: p. 61 |
Disc. AE: Rash... AEs leading to discontinuation/dose reduction: Rash (moderate, 1 patient) Sources: Page: p. 61 |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Wheezing | 1 patient | 300 mg single, oral Overdose Dose: 300 mg Route: oral Route: single Dose: 300 mg Co-administed with:: lorazepam(7 mg) Sources: |
unknown, 41 years n = 1 Health Status: unknown Age Group: 41 years Sex: M Population Size: 1 Sources: |
| Hypotension | 1 patient | 375 mg single, oral Overdose Dose: 375 mg Route: oral Route: single Dose: 375 mg Co-administed with:: simvastatin(fifteen 20-mg tablets) Sources: |
unhealthy, 84 years n = 1 Health Status: unhealthy Age Group: 84 years Sex: M Population Size: 1 Sources: |
| Hypotension | 0.7% Disc. AE |
50 mg 1 times / day steady, oral Recommended Dose: 50 mg, 1 times / day Route: oral Route: steady Dose: 50 mg, 1 times / day Sources: |
unhealthy, adult n = 765 Health Status: unhealthy Condition: heart failure Age Group: adult Population Size: 765 Sources: |
| Congestive cardiac failure | moderate, 1 patient Disc. AE |
20 mg 2 times / day multiple, oral Dose: 20 mg, 2 times / day Route: oral Route: multiple Dose: 20 mg, 2 times / day Sources: Page: p. 61 |
unhealthy, adult n = 54 Health Status: unhealthy Age Group: adult Population Size: 54 Sources: Page: p. 61 |
| Dizziness | 1.3% Disc. AE |
25 mg 2 times / day steady, oral Dose: 25 mg, 2 times / day Route: oral Route: steady Dose: 25 mg, 2 times / day Sources: |
unhealthy, adult n = 1156 Health Status: unhealthy Condition: severe heart failure Age Group: adult Population Size: 1156 Sources: |
| Abdominal distension | 1 patient Disc. AE |
6.25 mg 2 times / day multiple, oral Dose: 6.25 mg, 2 times / day Route: oral Route: multiple Dose: 6.25 mg, 2 times / day Sources: Page: p. 61 |
unhealthy, adult n = 54 Health Status: unhealthy Age Group: adult Population Size: 54 Sources: Page: p. 61 |
| Rash | moderate, 1 patient Disc. AE |
6.25 mg 2 times / day multiple, oral Dose: 6.25 mg, 2 times / day Route: oral Route: multiple Dose: 6.25 mg, 2 times / day Sources: Page: p. 61 |
unhealthy, adult n = 54 Health Status: unhealthy Age Group: adult Population Size: 54 Sources: Page: p. 61 |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Beta-blocker selectivity at cloned human beta 1- and beta 2-adrenergic receptors. | 1999 Apr |
|
| Carvedilol and lacidipine prevent cardiac hypertrophy and endothelin-1 gene overexpression after aortic banding. | 1999 Dec |
|
| Treatment with inverse agonists enhances baseline atrial contractility in transgenic mice with chronic beta2-adrenoceptor activation. | 1999 Jul |
|
| The pharmacokinetics of carvedilol and its metabolites after single and multiple dose oral administration in patients with hypertension and renal insufficiency. | 1999 Jun |
|
| Reducing readmissions for congestive heart failure. | 2001 Apr 15 |
|
| [Economic study of carvedilol in heart failure. A cost effectiveness study in France]. | 2001 Feb |
|
| Inhibitory effect of carvedilol in the high-conductance state of the mitochondrial permeability transition pore. | 2001 Feb 2 |
|
| Detection of low levels of the amorphous phase in crystalline pharmaceutical materials by thermally stimulated current spectrometry. | 2001 Jan |
|
| Impressive amelioration of clinical (NYHA class) and echocardiographic parameters in heart failure patients treated with amiodarone and carvedilol. | 2001 Jan |
|
| Effect of carvedilol on atrioventricular conduction in the ischemic heart. | 2001 Jan 26 |
|
| [Effects of carvedilol in rats with induced chronic kidney failure]. | 2001 Jan-Feb |
|
| Stereoselective effects of (R)- and (S)-carvedilol in humans. | 2001 Jul |
|
| Beta-blockers to reduce mortality in patients with systolic dysfunction: a meta-analysis. | 2001 Jun |
|
| Bucindolol, a nonselective beta 1- and beta 2-adrenergic receptor antagonist, decreases beta-adrenergic receptor density in cultured embryonic chick cardiac myocyte membranes. | 2001 Jun |
|
| Clinical Trials Update: CAPRICORN, COPERNICUS, MIRACLE, STAF, RITZ-2, RECOVER and RENAISSANCE and cachexia and cholesterol in heart failure. Highlights of the Scientific Sessions of the American College of Cardiology, 2001. | 2001 Jun |
|
| A cost-effectiveness analysis of bisoprolol for heart failure. | 2001 Jun |
|
| 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. | 2001 Jun 1 |
|
| Beta-blockade in chronic heart failure. | 2001 Jun 12 |
|
| Nebivolol, carvedilol and metoprolol do not influence cardiac Ca(2+) sensitivity. | 2001 Jun 22 |
|
| Predicting response to carvedilol for the treatment of heart failure: a multivariate retrospective analysis. | 2001 Mar |
|
| Are all beta-blockers the same for chronic heart failure? | 2001 Mar |
|
| What is the optimal medical management of ischemic heart failure? | 2001 Mar-Apr |
|
| Benefits of beta-blockers in heart failure: a class specific effect? | 2001 May |
|
| Mechanisms of carvedilol action in human congestive heart failure. | 2001 May |
|
| Effect of carvedilol on survival in severe chronic heart failure. | 2001 May 31 |
|
| Separation of carvedilol enantiomers in very small volumes of human plasma by capillary electrophoresis with laser-induced fluorescence. | 2001 May 5 |
|
| Economic impact of beta blockade in heart failure. | 2001 May 7 |
Sample Use Guides
Take with food. Individualize dosage and monitor during up-titration.• Heart failure: Start at 3.125 mg twice daily and increase to 6.25, 12.5, and then 25 mg twice daily over intervals of at least 2 weeks. Maintain lower doses if higher doses are not tolerated.• Left ventricular dysfunction following myocardial infarction: Start at 6.25 mg twice daily and increase to 12.5 mg then 25 mg twice daily afterintervals of 3 to 10 days. A lower starting dose or slower titration may be used.• Hypertension: Start at 6.25 mg twice daily and increase if needed for blood pressure control to 12.5 mg then 25 mg twice daily over intervals of 1 to 2 weeks.
Route of Administration:
Oral
Compared with the PDGF-stimulated control, DNA synthesis decreased significantly to 60.3% +/- 10.4% and 18.3% +/- 5.9% in the presence of 1 and 10 microM of carvedilol, respectively (P < 0.05, each). Carvedilol significantly inhibited the activity of VSMCs stimulated by ET-1 and ANG-II. The IC50 of carvedilol was 1-10 microM. CsA only inhibited VSMCs significantly in the PDGF-stimulated subgroup. The addition of CsA in the presence of carvedilol did not affect the inhibitory activity of carvedilol. The pattern of inhibition in the combined group was uniform and similar to that of the carvedilol alone group, regardless of the stimulator used.
| Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 17 00:30:26 UTC 2022
by
admin
on
Sat Dec 17 00:30:26 UTC 2022
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| Record UNII |
N9A00DJ8CM
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| Record Status |
Validated (UNII)
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| Record Version |
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SUB01074MIG
Created by
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11419372
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N9A00DJ8CM
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374779-41-6
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