U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry RACEMIC
Molecular Formula 2C15H25NO3.C4H4O4
Molecular Weight 650.8
Optical Activity ( + / - )
Defined Stereocenters 0 / 2
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of METOPROLOL FUMARATE

SMILES

OC(=O)\C=C\C(O)=O.COCCC1=CC=C(OCC(O)CNC(C)C)C=C1.COCCC2=CC=C(OCC(O)CNC(C)C)C=C2

InChI

InChIKey=BRIPGNJWPCKDQZ-WXXKFALUSA-N
InChI=1S/2C15H25NO3.C4H4O4/c2*1-12(2)16-10-14(17)11-19-15-6-4-13(5-7-15)8-9-18-3;5-3(6)1-2-4(7)8/h2*4-7,12,14,16-17H,8-11H2,1-3H3;1-2H,(H,5,6)(H,7,8)/b;;2-1+

HIDE SMILES / InChI

Molecular Formula C4H4O4
Molecular Weight 116.0722
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

Molecular Formula C15H25NO3
Molecular Weight 267.3639
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

Mrtoprolol is a beta-adrenergic receptor blocking agent. In vitro and in vivo animal studies have shown that it has a preferential effect on beta-1 adrenoreceptors, chiefly located in cardiac muscle. Clinical pharmacology studies have confirmed the beta-blocking activity of metoprolol in man, as shown by (1) reduction in heart rate and cardiac output at rest and upon exercise, (2) reduction of systolic blood pressure upon exercise, (3) inhibition of isoproterenol-induced tachycardia, and (4) reduction of reflex orthostatic tachycardia. Mrtoprolol is indicated for the treatment of hypertension, angina pectoris and myocardial infarction

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
LOPRESSOR

Approved Use

Hypertension Metoprolol tartrate tablets are indicated for the treatment of hypertension. They may be used alone or in combination with other antihypertensive agents. Angina Pectoris Metoprolol tartrate tablets are indicated in the long-term treatment of angina pectoris. Myocardial Infarction Metoprolol tartrate injection and tablets are indicated in the treatment of hemodynamically stable patients with definite or suspected acute myocardial infarction to reduce cardiovascular mortality. Treatment with intravenous metoprolol tartrate can be initiated as soon as the patient’s clinical condition allows (see DOSAGE AND ADMINISTRATION , CONTRAINDICATIONS , and WARNINGS ). Alternatively, treatment can begin within 3 to 10 days of the acute event (see DOSAGE AND ADMINISTRATION ).

Launch Date

1978
Primary
LOPRESSOR

Approved Use

Hypertension Metoprolol tartrate tablets are indicated for the treatment of hypertension. They may be used alone or in combination with other antihypertensive agents. Angina Pectoris Metoprolol tartrate tablets are indicated in the long-term treatment of angina pectoris. Myocardial Infarction Metoprolol tartrate injection and tablets are indicated in the treatment of hemodynamically stable patients with definite or suspected acute myocardial infarction to reduce cardiovascular mortality. Treatment with intravenous metoprolol tartrate can be initiated as soon as the patient’s clinical condition allows (see DOSAGE AND ADMINISTRATION , CONTRAINDICATIONS , and WARNINGS ). Alternatively, treatment can begin within 3 to 10 days of the acute event (see DOSAGE AND ADMINISTRATION ).

Launch Date

1978
Primary
LOPRESSOR

Approved Use

Hypertension Metoprolol tartrate tablets are indicated for the treatment of hypertension. They may be used alone or in combination with other antihypertensive agents. Angina Pectoris Metoprolol tartrate tablets are indicated in the long-term treatment of angina pectoris. Myocardial Infarction Metoprolol tartrate injection and tablets are indicated in the treatment of hemodynamically stable patients with definite or suspected acute myocardial infarction to reduce cardiovascular mortality. Treatment with intravenous metoprolol tartrate can be initiated as soon as the patient’s clinical condition allows (see DOSAGE AND ADMINISTRATION , CONTRAINDICATIONS , and WARNINGS ). Alternatively, treatment can begin within 3 to 10 days of the acute event (see DOSAGE AND ADMINISTRATION ).

Launch Date

1978
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
76 ng/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
METOPROLOL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
279 ng × h/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
METOPROLOL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
2.8 h
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
METOPROLOL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
9 h
unknown
METOPROLOL plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
90%
unknown
METOPROLOL plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
5000 mg single, oral
Overdose
Dose: 5000 mg
Route: oral
Route: single
Dose: 5000 mg
Sources:
unknown, 39 years
Health Status: unknown
Age Group: 39 years
Sex: F
Sources:
Disc. AE: Bradycardia...
AEs leading to
discontinuation/dose reduction:
Bradycardia (1 patient)
Sources:
7500 mg single, oral
Overdose
Dose: 7500 mg
Route: oral
Route: single
Dose: 7500 mg
Sources:
unknown, adult
Health Status: unknown
Age Group: adult
Sex: unknown
Sources:
Disc. AE: Death...
AEs leading to
discontinuation/dose reduction:
Death (grade 5, 1 patient)
Sources:
AEs

AEs

AESignificanceDosePopulation
Bradycardia 1 patient
Disc. AE
5000 mg single, oral
Overdose
Dose: 5000 mg
Route: oral
Route: single
Dose: 5000 mg
Sources:
unknown, 39 years
Health Status: unknown
Age Group: 39 years
Sex: F
Sources:
Death grade 5, 1 patient
Disc. AE
7500 mg single, oral
Overdose
Dose: 7500 mg
Route: oral
Route: single
Dose: 7500 mg
Sources:
unknown, adult
Health Status: unknown
Age Group: adult
Sex: unknown
Sources:
Overview

OverviewOther

Other InhibitorOther SubstrateOther Inducer

Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
yes [Ki 570 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
major
yes (co-administration study)
Comment: coadministration of quinidine 100 mg and immediate release metoprolol 200 mg tripled the concentration of S-metoprolol and doubled the metoprolol elimination half-life; Coadministration of metoprolol with gefitinib resulted in a 35% increase in the metoprolol area under plasma concentration-time curve from time zero to the time of the last quantifiable concentration; paroxetine increased the AUC of metoprolol three to five times, and significantly decreased systolic blood pressure and heart rate of patients;
Page: 3.0
minor
minor
minor
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Calcineurin-GATA4 pathway is involved in beta-adrenergic agonist-responsive endothelin-1 transcription in cardiac myocytes.
2001-09-14
Stereospecific pharmacokinetics and pharmacodynamics of beta-adrenergic blockers in humans.
2001-07-24
Enantiomeric separation of metoprolol and alpha-hydroxymetoprolol by liquid chromatography and fluorescence detection using a chiral stationary phase.
2001-07-15
beta(1)-Adrenoceptor antibodies induce positive inotropic response in isolated cardiomyocytes.
2001-07-06
Influence of beta-adrenoceptor antagonists on the pharmacokinetics of rizatriptan, a 5-HT1B/1D agonist: differential effects of propranolol, nadolol and metoprolol.
2001-07
Statistical issues relating to international differences in clinical trials.
2001-07
Catecholamines stimulate interleukin-6 synthesis in rat cardiac fibroblasts.
2001-07
Behavioral-independent features of complex heartbeat dynamics.
2001-06-25
Nebivolol, carvedilol and metoprolol do not influence cardiac Ca(2+) sensitivity.
2001-06-22
Metoprolol attenuates postischemic depressed myocardial function in papillary muscles isolated from normal and postinfarction rat hearts.
2001-06-22
Cardiac autonomic denervation and functional response to neurotoxins during acute experimental Chagas' disease in rats.
2001-06-20
Beta-blockade in chronic heart failure.
2001-06-12
Effect of ramipril vs amlodipine on renal outcomes in hypertensive nephrosclerosis: a randomized controlled trial.
2001-06-06
The juxtaglomerular apparatus in young type-1 diabetic patients with microalbuminuria. Effect of antihypertensive treatment.
2001-06
Effect of lipophilicity on in vivo iontophoretic delivery. II. Beta-blockers.
2001-06
Cardioprotective effect of propranolol from alcohol-induced heart muscle damage as assessed by plasma cardiac troponin-t.
2001-06
Beta-blockers to reduce mortality in patients with systolic dysfunction: a meta-analysis.
2001-06
Circadian variation of heart rate variability and the rate of autonomic change in the morning hours in healthy subjects and angina patients.
2001-06
Differing beta-blocking effects of carvedilol and metoprolol.
2001-06
Comparative effects of carvedilol and metoprolol on left ventricular ejection fraction in heart failure: results of a meta-analysis.
2001-06
Effects of digoxin, furosemide, enalaprilat and metoprolol on endothelial function in young normotensive subjects.
2001-05-31
Reversible renal impairment induced by treatment with the angiotensin II receptor antagonist candesartan in a patient with bilateral renal artery stenosis.
2001-05-17
Economic impact of beta blockade in heart failure.
2001-05-07
Enantioselective determination of metoprolol and major metabolites in human urine by capillary electrophoresis.
2001-05-05
Effects of direct sympathetic and vagus nerve stimulation on the physiology of the whole heart--a novel model of isolated Langendorff perfused rabbit heart with intact dual autonomic innervation.
2001-05
An optimized methodology for combined phenotyping and genotyping on CYP2D6 and CYP2C19.
2001-05
Benefits of beta-blockers in heart failure: a class specific effect?
2001-05
Overview of the results of recent beta blocker trials.
2001-05
Metoprolol CR/XL in the treatment of chronic heart failure.
2001-05
Angerlike behavioral state potentiates myocardial ischemia-induced T-wave alternans in canines.
2001-05
Carvedilol in the treatment of chronic heart failure.
2001-05
Carvedilol versus other beta-blockers in heart failure.
2001-05
Metoprolol-paroxetine interaction in human liver microsomes: stereoselective aspects and prediction of the in vivo interaction.
2001-05
Reducing readmissions for congestive heart failure.
2001-04-15
Influence of phenylalanine-481 substitutions on the catalytic activity of cytochrome P450 2D6.
2001-04-15
Quantitative structure-retention and retention-activity relationships of beta-blocking agents by micellar liquid chromatography.
2001-04-06
Low-dose metoprolol CR/XL and fluvastatin slow progression of carotid intima-media thickness: Main results from the Beta-Blocker Cholesterol-Lowering Asymptomatic Plaque Study (BCAPS).
2001-04-03
Comparative effects of three beta blockers (atenolol, metoprolol, and propranolol) on survival after acute myocardial infarction.
2001-04-01
Beta-blocker treatment in heart failure.
2001-04
Syncope in pharmacologically unmasked Brugada syndrome: indication for an implantable defibrillator or an unresolved dilemma?
2001-04
Giant R-waves in a patient with an acute inferior myocardial infarction.
2001-04
Characterization of beta(1)-selectivity, adrenoceptor-G(s)-protein interaction and inverse agonism of nebivolol in human myocardium.
2001-04
A comparative study of oral acetylsalicyclic acid and metoprolol for the prophylactic treatment of migraine. A randomized, controlled, double-blind, parallel group phase III study.
2001-03
[Adrenergic beta inhibitors in heart insufficiency: which and when?].
2001-03
Anti beta1-adrenoceptor autoantibodies analyzed in spontaneously beating neonatal rat heart myocyte cultures-comparison of methods.
2001-03
Effect of beta blockers on mortality and morbidity in persons treated for congestive heart failure.
2001-03
Anti-ischaemic efficacy and tolerability of trimetazidine administered to patients with angina pectoris: results of three studies.
2001-02
Low-dose ACE with alpha- or beta-adrenergic receptor inhibitors have beneficial SHR cardiovascular effects.
2001-01
Sotalol vs metoprolol for ventricular rate control in patients with chronic atrial fibrillation who have undergone digitalization: a single-blinded crossover study.
2001-01
Regression of left ventricular mass with captopril and metoprolol, and the effects on glucose and lipid metabolism.
2001
Patents

Sample Use Guides

Hypertension The dosage of Lopressor should be individualized. Lopressor should be taken with or immediately following meals. The usual initial dosage is 100 mg daily in single or divided doses, whether used alone or added to a diuretic. The dosage may be increased at weekly (or longer) intervals until optimum blood pressure reduction is achieved. In general, the maximum effect of any given dosage level will be apparent after 1 week of therapy. The effective dosage range is 100-450 mg per day. Dosages above 450 mg per day have not been studied. While once-daily dosing is effective and can maintain a reduction in blood pressure throughout the day, lower doses (especially 100 mg) may not maintain a full effect at the end of the 24-hour period, and larger or more frequent daily doses may be required. This can be evaluated by measuring blood pressure near the end of the dosing interval to determine whether satisfactory control is being maintained throughout the day. Beta1 selectivity diminishes as the dose of Lopressor is increased. Angina Pectoris The dosage of Lopressor should be individualized. Lopressor should be taken with or immediately following meals. The usual initial dosage is 100 mg daily, given in two divided doses. The dosage may be gradually increased at weekly intervals until optimum clinical response has been obtained or there is pronounced slowing of the heart rate. The effective dosage range is 100-400 mg per day. Dosages above 400 mg per day have not been studied. If treatment is to be discontinued, the dosage should be reduced gradually over a period of 1-2 weeks (see WARNINGS). Myocardial Infarction Early Treatment: During the early phase of definite or suspected acute myocardial infarction, treatment with Lopressor can be initiated as soon as possible after the patient’s arrival in the hospital. Such treatment should be initiated in a coronary care or similar unit immediately after the patient’s hemodynamic condition has stabilized. Treatment in this early phase should begin with the intravenous administration of three bolus injections of 5 mg of Lopressor each; the injections should be given at approximately 2-minute intervals. During the intravenous administration of Lopressor, blood pressure, heart rate, and electrocardiogram should be carefully monitored. In patients who tolerate the full intravenous dose (15 mg), Lopressor tablets, 50 mg every 6 hours, should be initiated 15 minutes after the last intravenous dose and continued for 48 hours. Thereafter, patients should receive a maintenance dosage of 100 mg twice daily (see Late Treatment below). Patients who appear not to tolerate the full intravenous dose should be started on Lopressor tablets either 25 mg or 50 mg every 6 hours (depending on the degree of intolerance) 15 minutes after the last intravenous dose or as soon as their clinical condition allows. In patients with severe intolerance, treatment with Lopressor should be discontinued (see WARNINGS). Late Treatment: Patients with contraindications to treatment during the early phase of suspected or definite myocardial infarction, patients who appear not to tolerate the full early treatment, and patients in whom the physician wishes to delay therapy for any other reason should be started on Lopressor tablets, 100 mg twice daily, as soon as their clinical condition allows. Therapy should be continued for at least 3 months. Although the efficacy of Lopressor beyond 3 months has not been conclusively established, data from studies with other beta blockers suggest that treatment should be continued for 1-3 years. Note: Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Route of Administration: Other
0.01 to 0.1 uM metoprolol increased osteoblast proliferation, alkaline phosphatase activity, and calcium mineralization, and promoted the expression of osteogenic genes.
Substance Class Chemical
Created
by admin
on Mon Mar 31 18:27:53 GMT 2025
Edited
by admin
on Mon Mar 31 18:27:53 GMT 2025
Record UNII
IO1C09Z674
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
LOPRESSOR OROS
Preferred Name English
METOPROLOL FUMARATE
MART.   ORANGE BOOK   USAN   USP   USP-RS   WHO-DD  
USAN  
Official Name English
CGP-2175C
Code English
METOPROLOL FUMARATE [USAN]
Common Name English
METOPROLOL FUMARATE [USP MONOGRAPH]
Common Name English
METOPROLOL FUMARATE [MART.]
Common Name English
METOPROLOL FUMARATE [ORANGE BOOK]
Common Name English
METOPROLOL FUMARATE [USP-RS]
Common Name English
2-PROPANOL, 1-(4-(2-METHOXYETHYL)PHENOXY)-3-((1-METHYLETHYL)AMINO)-, (2E)-2-BUTENEDIOATE (2:1)
Systematic Name English
(±)-1-(ISOPROPYLAMINO)-3-(P-(2-METHOXYETHYL)PHENOXY)-2-PROPANOL FUMARATE (2:1) (SALT)
Common Name English
CGP 2175C
Code English
2-PROPANOL, 1-(4-(2-METHOXYETHYL)PHENOXY)-3-((1-METHYLETHYL)AMINO)-, (±)-, (E)-2-BUTANEDIOATE (2:1) (SALT)
Common Name English
Metoprolol fumarate [WHO-DD]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C29576
Created by admin on Mon Mar 31 18:27:53 GMT 2025 , Edited by admin on Mon Mar 31 18:27:53 GMT 2025
Code System Code Type Description
RXCUI
102313
Created by admin on Mon Mar 31 18:27:53 GMT 2025 , Edited by admin on Mon Mar 31 18:27:53 GMT 2025
PRIMARY RxNorm
SMS_ID
100000090418
Created by admin on Mon Mar 31 18:27:53 GMT 2025 , Edited by admin on Mon Mar 31 18:27:53 GMT 2025
PRIMARY
CAS
80274-67-5
Created by admin on Mon Mar 31 18:27:53 GMT 2025 , Edited by admin on Mon Mar 31 18:27:53 GMT 2025
PRIMARY
EPA CompTox
DTXSID301027711
Created by admin on Mon Mar 31 18:27:53 GMT 2025 , Edited by admin on Mon Mar 31 18:27:53 GMT 2025
PRIMARY
CAS
119637-66-0
Created by admin on Mon Mar 31 18:27:53 GMT 2025 , Edited by admin on Mon Mar 31 18:27:53 GMT 2025
SUPERSEDED
NCI_THESAURUS
C66133
Created by admin on Mon Mar 31 18:27:53 GMT 2025 , Edited by admin on Mon Mar 31 18:27:53 GMT 2025
PRIMARY
CAS
79985-31-2
Created by admin on Mon Mar 31 18:27:53 GMT 2025 , Edited by admin on Mon Mar 31 18:27:53 GMT 2025
SUPERSEDED
RS_ITEM_NUM
1441287
Created by admin on Mon Mar 31 18:27:53 GMT 2025 , Edited by admin on Mon Mar 31 18:27:53 GMT 2025
PRIMARY
USAN
BB-64
Created by admin on Mon Mar 31 18:27:53 GMT 2025 , Edited by admin on Mon Mar 31 18:27:53 GMT 2025
PRIMARY
ChEMBL
CHEMBL13
Created by admin on Mon Mar 31 18:27:53 GMT 2025 , Edited by admin on Mon Mar 31 18:27:53 GMT 2025
PRIMARY
FDA UNII
IO1C09Z674
Created by admin on Mon Mar 31 18:27:53 GMT 2025 , Edited by admin on Mon Mar 31 18:27:53 GMT 2025
PRIMARY
DRUG BANK
DBSALT001329
Created by admin on Mon Mar 31 18:27:53 GMT 2025 , Edited by admin on Mon Mar 31 18:27:53 GMT 2025
PRIMARY
EVMPD
SUB03273MIG
Created by admin on Mon Mar 31 18:27:53 GMT 2025 , Edited by admin on Mon Mar 31 18:27:53 GMT 2025
PRIMARY
PUBCHEM
6440651
Created by admin on Mon Mar 31 18:27:53 GMT 2025 , Edited by admin on Mon Mar 31 18:27:53 GMT 2025
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
Related Record Type Details
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
Related Record Type Details
ACTIVE MOIETY