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Details

Stereochemistry RACEMIC
Molecular Formula C24H26N2O4.H2O.H3O4P
Molecular Weight 522.4856
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CARVEDILOL PHOSPHATE MONOHYDRATE

SMILES

COc1ccccc1OCCNCC(COc2cccc3c2c4ccccc4[nH]3)O.OP(=O)(O)O.O

InChI

InChIKey=JAYBFQXVKDGMFT-UHFFFAOYSA-N
InChI=1S/C24H26N2O4.H3O4P.H2O/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;1-5(2,3)4;/h2-12,17,25-27H,13-16H2,1H3;(H3,1,2,3,4);1H2

HIDE SMILES / InChI

Molecular Formula H3O4P
Molecular Weight 97.9952
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula H2O
Molecular Weight 18.0153
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C24H26N2O4
Molecular Weight 406.4751
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

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.

Originator

Curator's Comment:: reference retrieved from http://www.drugfuture.com/chemdata/carvedilol.html

Approval Year

Targets

Targets

Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
COREG

Approved Use

COREG® (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 Date

8.1103677E11
Primary
COREG

Approved Use

COREG® (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 Date

8.1103677E11
Primary
COREG

Approved Use

COREG® (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 Date

8.1103677E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
18.4 ng/mL
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
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
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

AUC

ValueDoseCo-administeredAnalytePopulation
94.3 ng × h/mL
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
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
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

Doses

DosePopulationAdverse 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...
Other AEs:
Wheezing (1 patient)
Sources:
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...
Other AEs:
Hypotension (1 patient)
Sources:
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

AEs

AESignificanceDosePopulation
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

PubMed

TitleDatePubMed
Levosimendan.
2001
CAPRICORN: a story of alpha allocation and beta-blockers in left ventricular dysfunction post-MI.
2001 Apr
Characterization of beta(1)-selectivity, adrenoceptor-G(s)-protein interaction and inverse agonism of nebivolol in human myocardium.
2001 Apr
Carvedilol as therapy in pediatric heart failure: an initial multicenter experience.
2001 Apr
Carvedilol--a new dimension in pediatric heart failure therapy.
2001 Apr
50th Annual scientific sessions of the American college of cardiology.
2001 Apr 10
Reducing readmissions for congestive heart failure.
2001 Apr 15
Detection of low levels of the amorphous phase in crystalline pharmaceutical materials by thermally stimulated current spectrometry.
2001 Jan
[Effects of carvedilol in rats with induced chronic kidney failure].
2001 Jan-Feb
Effects of carvedilol on left ventricular function, mass, and scintigraphic findings in isolated left ventricular non-compaction.
2001 Jul
Catecholamines stimulate interleukin-6 synthesis in rat cardiac fibroblasts.
2001 Jul
Stereoselective effects of (R)- and (S)-carvedilol in humans.
2001 Jul
Radical-scavenging and iron-chelating properties of carvedilol, an antihypertensive drug with antioxidative activity.
2001 Jul 15
Using isoproterenol stress echocardiography to predict the response to carvedilol in patients with dilated cardiomyopathy.
2001 Jun
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
Differing beta-blocking effects of carvedilol and metoprolol.
2001 Jun
Influence of carvedilol on the benefits of physical training in patients with moderate chronic heart failure.
2001 Jun
Carvedilol increases plasma vascular endothelial growth factor (VEGF) in patients with chronic heart failure.
2001 Jun
Plasma brain natriuretic peptide as a novel therapeutic indicator in idiopathic dilated cardiomyopathy during beta-blocker therapy: a potential of hormone-guided treatment.
2001 Jun
Comparative effects of carvedilol and metoprolol on left ventricular ejection fraction in heart failure: results of a meta-analysis.
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
Protective effect of carvedilol on chenodeoxycholate induction of the permeability transition pore.
2001 Jun 1
Beta-blocker trials seem to be in conflict.
2001 Jun 12
Beta-blockade in chronic heart failure.
2001 Jun 12
Relationship between tumor necrosis factor-alpha production and oxidative stress in the failing hearts of patients with dilated cardiomyopathy.
2001 Jun 15
Nebivolol, carvedilol and metoprolol do not influence cardiac Ca(2+) sensitivity.
2001 Jun 22
Random research.
2001 Jun 26
[Options in drug combinations].
2001 Mar
[Adrenergic beta inhibitors in heart insufficiency: which and when?].
2001 Mar
Determination of carvedilol in human cardiac tissue by high-performance liquid chromatography.
2001 Mar
[Severe heart failure. Carvedilol lowers mortality].
2001 Mar 1
Benefits of beta-blockers in heart failure: a class specific effect?
2001 May
Does intention-to-treat analysis answer all questions in long-term mortality trials? Considerations on the basis of the ANZ trial.
2001 May
Mechanisms of carvedilol action in human congestive heart failure.
2001 May
Overview of the results of recent beta blocker trials.
2001 May
Influence of carvedilol on hospitalizations in heart failure: incidence, resource utilization and costs. U.S. Carvedilol Heart Failure Study Group.
2001 May
Carvedilol in the treatment of chronic heart failure.
2001 May
Carvedilol versus other beta-blockers in heart failure.
2001 May
Myocardial free fatty acid and glucose use after carvedilol treatment in patients with congestive heart failure.
2001 May 22
Racial differences in the response to drugs--pointers to genetic differences.
2001 May 3
Race and the response to adrenergic blockade with carvedilol in patients with chronic heart failure.
2001 May 3
Expanding indications for beta-blockers in heart failure.
2001 May 31
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
Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the CAPRICORN randomised trial.
2001 May 5
Current role of beta-adrenergic blockers in the management of chronic heart failure.
2001 May 7
Economic impact of beta blockade in heart failure.
2001 May 7
Patents

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 Sat Jun 26 10:39:21 UTC 2021
Edited
by admin
on Sat Jun 26 10:39:21 UTC 2021
Record UNII
4S19O2F64L
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
CARVEDILOL PHOSPHATE MONOHYDRATE
Common Name English
2-PROPANOL, 1-(9H-CARBAZOL-4-YLOXY)-3-((2-(2-METHOXYPHENOXY)ETHYL)AMINO)-, PHOSPHATE, HYDRATE (1:1:1)
Systematic Name English
Code System Code Type Description
PUBCHEM
23649704
Created by admin on Sat Jun 26 10:39:22 UTC 2021 , Edited by admin on Sat Jun 26 10:39:22 UTC 2021
PRIMARY
FDA UNII
4S19O2F64L
Created by admin on Sat Jun 26 10:39:22 UTC 2021 , Edited by admin on Sat Jun 26 10:39:22 UTC 2021
PRIMARY
CAS
1196658-85-1
Created by admin on Sat Jun 26 10:39:22 UTC 2021 , Edited by admin on Sat Jun 26 10:39:22 UTC 2021
PRIMARY
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