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Identification
NameMetoprolol
Accession NumberDB00264  (APRD00208)
Typesmall molecule
Groupsapproved, investigational
Description

Metoprolol is a cardioselective β1-adrenergic blocking agent used for acute myocardial infarction (MI), heart failure, angina pectoris and mild to moderate hypertension. It may also be used for supraventricular and tachyarrhythmias and prophylaxis for migraine headaches. Metoprolol is structurally similar to bisoprolol, acebutolol and atenolol in that it has two substituents in the para position of the benzene ring. The β1-selectivity of these agents is thought to be due in part to the large substituents in the para position. At low doses, metoprolol selectively blocks cardiac β1-adrenergic receptors with little activity against β2-adrenergic receptors of the lungs and vascular smooth muscle. Receptor selectivity decreases with higher doses. Unlike propranolol and pindolol, metoprolol does not exhibit membrane-stabilizing or intrinsic sympathomimetic activity. Membrane-stabilizing effects are only observed at doses much higher than those needed for β-adrenergic blocking activity. Metoprolol possesses a single chiral centre and is administered as a racemic mixture.

Structure
Thumb
Synonyms
SynonymLanguageCode
(RS)-MetoprololNot AvailableNot Available
1-(isopropylamino)-3-[4-(2-methoxyethyl)phenoxy]propan-2-olNot AvailableNot Available
Salts
Name/CAS Structure Properties
Metoprolol succinate
Thumb Not applicable DBSALT000863
Metoprolol tartrate
Thumb Not applicable DBSALT000862
Brand names
NameCompany
CorvitolNot Available
DutoprolNot Available
LopressorNovartis
MinaxNot Available
SelokeenNot Available
TOPROLNot Available
Toprol-XLNot Available
TOPROLXLNot Available
Brand mixturesNot Available
Categories
CAS number37350-58-6
WeightAverage: 267.3639
Monoisotopic: 267.183443671
Chemical FormulaC15H25NO3
InChI KeyIUBSYMUCCVWXPE-UHFFFAOYSA-N
InChI
InChI=1S/C15H25NO3/c1-12(2)16-10-14(17)11-19-15-6-4-13(5-7-15)8-9-18-3/h4-7,12,14,16-17H,8-11H2,1-3H3
IUPAC Name
{2-hydroxy-3-[4-(2-methoxyethyl)phenoxy]propyl}(propan-2-yl)amine
SMILES
COCCC1=CC=C(OCC(O)CNC(C)C)C=C1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassPhenols and Derivatives
Direct parentTyrosols and Derivatives
Alternative parentsPhenol Ethers; Alkyl Aryl Ethers; Secondary Alcohols; 1,2-Aminoalcohols; Polyamines; Dialkylamines
Substituentsphenol ether; alkyl aryl ether; 1,2-aminoalcohol; secondary alcohol; secondary amine; secondary aliphatic amine; ether; polyamine; amine; alcohol; organonitrogen compound
Classification descriptionThis compound belongs to the tyrosols and derivatives. These are compounds containing an hydroxyethyl group atached to the C4 carbon of a phenol group.
Pharmacology
IndicationFor the management of acute myocardial infarction, angina pectoris, heart failure and mild to moderate hypertension. May be used to treat supraventricular and tachyarrhythmias and as prophylaxis for migraine headaches.
PharmacodynamicsMetoprolol, a competitive, beta1-selective (cardioselective) adrenergic antagonist, is similar to atenolol in its moderate lipid solubility, lack of intrinsic sympathomimetic activity (ISA), and weak membrane stabilizing activity (MSA).
Mechanism of actionMetoprolol competes with adrenergic neurotransmitters such as catecholamines for binding at beta(1)-adrenergic receptors in the heart. Beta(1)-receptor blockade results in a decrease in heart rate, cardiac output, and blood pressure.
AbsorptionRapid and complete, 50%
Volume of distributionNot Available
Protein binding12%
Metabolism

Primarily hepatic

SubstrateEnzymesProduct
Metoprolol
alpha-HydroxymetoprololDetails
Route of eliminationLess than 5% of an oral dose of metoprolol is recovered unchanged in the urine; the rest is excreted by the kidneys as metabolites that appear to have no beta-blocking activity.
Half life3-7 hours
ClearanceNot Available
ToxicityLD50=5500 mg/kg (orally in rats), toxic effects include bradycardia, hypotension, bronchospasm, and cardiac failure. LD50=2090 mg/kg (orally in mice)
Affected organisms
  • Humans and other mammals
PathwaysNot Available
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 therapy12844134
SNP Mediated Adverse Drug Reactions
Interacting Gene/EnzymeSNP RS IDAllele nameDefining changeAdverse ReactionReference(s)
Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635
rs3892097 CYP2D6*4A alleleIncreased risk of slow heart rate (bradycardia)18784654
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9854
Blood Brain Barrier - 0.8426
Caco-2 permeable + 0.6895
P-glycoprotein substrate Substrate 0.7317
P-glycoprotein inhibitor I Non-inhibitor 0.8182
P-glycoprotein inhibitor II Non-inhibitor 0.8382
Renal organic cation transporter Non-inhibitor 0.8418
CYP450 2C9 substrate Non-substrate 0.81
CYP450 2D6 substrate Substrate 0.8918
CYP450 3A4 substrate Non-substrate 0.6527
CYP450 1A2 substrate Non-inhibitor 0.7018
CYP450 2C9 substrate Non-inhibitor 0.8691
CYP450 2D6 substrate Non-inhibitor 0.7909
CYP450 2C19 substrate Non-inhibitor 0.9555
CYP450 3A4 substrate Non-inhibitor 0.9476
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9897
Ames test Non AMES toxic 0.9163
Carcinogenicity Non-carcinogens 0.9387
Biodegradation Not ready biodegradable 0.8544
Rat acute toxicity 1.9180 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.8368
hERG inhibition (predictor II) Non-inhibitor 0.8202
Pharmacoeconomics
Manufacturers
  • Novartis pharmaceuticals corp
  • Kv pharmaceutical co
  • Sandoz inc
  • Watson laboratories inc florida
  • Wockhardt ltd
  • Astrazeneca lp
  • Bedford laboratories
  • Hikma farmaceutica (portugal) sa
  • Hospira inc
  • Luitpold pharmaceuticals inc
  • Sagent strides llc
  • Sandoz canada inc
  • Watson laboratories inc
  • Apothecon inc div bristol myers squibb
  • Aurobindo pharma ltd
  • Caraco pharmaceutical laboratories ltd
  • Ipca laboratories ltd
  • Mutual pharmaceutical co inc
  • Mylan pharmaceuticals inc
  • Purepac pharmaceutical co
  • Solco healthcare us llc
  • Teva pharmaceuticals usa inc
  • Teva pharmaceuticals usa
Packagers
Dosage forms
FormRouteStrength
LiquidIntravenous
SolutionIntravenous
TabletOral
Tablet, extended releaseOral
Prices
Unit descriptionCostUnit
Metoprolol tartrate powder5.51USDg
Lopressor 5 mg/5 ml ampul3.85USDml
Lopressor hct 100-25 tablet3.21USDtablet
Toprol XL 200 mg 24 Hour tablet3.08USDtablet
Lopressor HCT 100-50 mg tablet3.06USDtablet
Toprol xl 200 mg tablet2.96USDtablet
Lopressor hct 100-50 tablet2.82USDtablet
Lopressor 100 mg tablet2.75USDtablet
Metoprolol Succinate 200 mg 24 Hour tablet2.62USDtablet
Metoprolol succ er 200 mg tablet2.29USDtablet
Lopressor HCT 100-25 mg tablet2.21USDtablet
Lopressor HCT 50-25 mg tablet2.14USDtablet
Lopressor hct 50-25 tablet2.06USDtablet
Toprol XL 100 mg 24 Hour tablet1.93USDtablet
Toprol xl 100 mg tablet1.86USDtablet
Lopressor 50 mg tablet1.81USDtablet
Metoprolol Succinate 100 mg 24 Hour tablet1.53USDtablet
Metoprolol succ er 100 mg tablet1.44USDtablet
Toprol XL 25 mg 24 Hour tablet1.43USDtablet
Toprol XL 50 mg 24 Hour tablet1.43USDtablet
Lopresor 1 mg/ml1.29USDml
Toprol xl 25 mg tablet1.24USDtablet
Toprol xl 50 mg tablet1.24USDtablet
Metoprolol Succinate 25 mg 24 Hour tablet1.17USDtablet
Metoprolol Succinate 50 mg 24 Hour tablet1.13USDtablet
Metoprolol succ er 50 mg tablet0.9USDtablet
Metoprolol succ er 25 mg tablet0.87USDtablet
Metoprolol tartrate 100 mg tablet0.8USDtablet
Toprol xl 100 mg tablet sa0.8USDtablet
Lopresor 100 mg Tablet0.61USDtablet
Lopresor Sr 200 mg Sustained-Release Tablet0.61USDtablet
Metoprolol tartrate 50 mg tablet0.56USDtablet
Metoprolol tartrate 25 mg tablet0.34USDtablet
Apo-Metoprolol Sr 200 mg Sustained-Release Tablet0.34USDtablet
Lopresor Sr 100 mg Sustained-Release Tablet0.34USDtablet
Sandoz Metoprolol Sr 200 mg Sustained-Release Tablet0.34USDtablet
Lopresor 50 mg Tablet0.3USDtablet
Apo-Metoprolol (Type L) 100 mg Tablet0.23USDtablet
Apo-Metoprolol 100 mg Tablet0.23USDtablet
Mylan-Metoprolol (Type L) 100 mg Tablet0.23USDtablet
Novo-Metoprol (Fc) 100 mg Tablet0.23USDtablet
Novo-Metoprol 100 mg Tablet0.23USDtablet
Nu-Metop 100 mg Tablet0.23USDtablet
Pms-Metoprolol-L 100 mg Tablet0.23USDtablet
Sandoz Metoprolol (Type L) 100 mg Tablet0.23USDtablet
Apo-Metoprolol Sr 100 mg Sustained-Release Tablet0.19USDtablet
Sandoz Metoprolol Sr 100 mg Sustained-Release Tablet0.19USDtablet
Apo-Metoprolol (Type L) 50 mg Tablet0.13USDtablet
Apo-Metoprolol 50 mg Tablet0.13USDtablet
Mylan-Metoprolol (Type L) 50 mg Tablet0.13USDtablet
Novo-Metoprol (Fc) 50 mg Tablet0.13USDtablet
Novo-Metoprol 50 mg Tablet0.13USDtablet
Nu-Metop 50 mg Tablet0.13USDtablet
Pms-Metoprolol-L 50 mg Tablet0.13USDtablet
Sandoz Metoprolol (Type L) 50 mg Tablet0.13USDtablet
Apo-Metoprolol 25 mg Tablet0.07USDtablet
Pms-Metoprolol-L 25 mg Tablet0.07USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point120 °C (tartarate salt)Not Available
water solubility1.69E+004 mg/L (at 25 °C)MCFARLAND,JW ET AL. (2001)
logP1.88HANSCH,C ET AL. (1995)
Caco2 permeability-4.59ADME Research, USCD
Predicted Properties
PropertyValueSource
water solubility4.02e-01 g/lALOGPS
logP1.8ALOGPS
logP1.76ChemAxon
logS-2.8ALOGPS
pKa (strongest acidic)14.09ChemAxon
pKa (strongest basic)9.67ChemAxon
physiological charge1ChemAxon
hydrogen acceptor count4ChemAxon
hydrogen donor count2ChemAxon
polar surface area50.72ChemAxon
rotatable bond count9ChemAxon
refractivity76.7ChemAxon
polarizability31.9ChemAxon
number of rings1ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraMS/MS1D NMR2D NMR
References
Synthesis Reference

DrugSyn.org

US3998790
General Reference
  1. : Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF) Lancet. 1999 Jun 12;353(9169):2001-7. Pubmed
External Links
ResourceLink
KEGG DrugD02358
KEGG CompoundC07202
PubChem Compound4171
PubChem Substance46506211
ChemSpider4027
BindingDB25756
ChEBI6904
ChEMBLCHEMBL13
Therapeutic Targets DatabaseDAP000481
PharmGKBPA450480
IUPHAR553
Guide to Pharmacology553
Drug Product Database2253518
RxListhttp://www.rxlist.com/cgi/generic/metopxl.htm
Drugs.comhttp://www.drugs.com/metoprolol.html
WikipediaMetoprolol
ATC CodesC07AB02C07AB52
AHFS Codes
  • 24:24.00
PDB EntriesNot Available
FDA labelshow(439 KB)
MSDSshow(73.9 KB)
Interactions
Drug Interactions
Drug
AcetohexamideThe beta-blocker, metoprolol, may decrease symptoms of hypoglycemia.
ChlorpropamideThe beta-blocker, metoprolol, may decrease symptoms of hypoglycemia.
CimetidineCimetidine may increase the serum concentration of metoprolol by decreasing its metabolism.
CitalopramThe SSRI, citalopram, may increase the bradycardic effect of the beta-blocker, metoprolol.
ClonidineIncreased hypertension when clonidine stopped
DihydroergotamineIschemia with risk of gangrene
DiltiazemIncreased risk of bradycardia
DisopyramideThe beta-blocker, metoprolol, may increase adverse effects of disopyramide.
DronedaroneMetoprolol is a CYP2D6 substrate and because dronedarone inhibits this enzyme, will increase metoprolol exposure 1.6-fold. Lower dose of metoprolol.
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, metoprolol.
FenoterolAntagonism
FluoxetineThe SSRI, fluoxetine, may increase the bradycardic effect of the beta-blocker, metoprolol.
FormoterolAntagonism
GliclazideThe beta-blocker, metoprolol, may decrease symptoms of hypoglycemia.
GlipizideThe beta-blocker, metoprolol, may decrease symptoms of hypoglycemia.
GlisoxepideThe beta-blocker, metoprolol, may decrease symptoms of hypoglycemia.
GlyburideThe beta-blocker, metoprolol, may decrease symptoms of hypoglycemia.
GlycodiazineThe beta-blocker, metoprolol, may decrease symptoms of hypoglycemia.
HydralazineIncreased effect of both drugs
IbuprofenRisk of inhibition of renal prostaglandins
IndomethacinRisk of inhibition of renal prostaglandins
Insulin GlargineThe beta-blocker, metoprolol, may decrease symptoms of hypoglycemia.
IsoprenalineAntagonism
LidocaineThe beta-blocker, metoprolol, may increase the effect and toxicity of lidocaine
MethysergideIschemia with risk of gangrene
MirabegronMirabegron is a moderate CYP2D6 inhibitor and may cause an increase in exposure of CYP2D6 substrates. Monitor concomitant therapy closely.
OrciprenalineAntagonism
ParoxetineThe SSRI increases the effect of the beta-blocker
PhenobarbitalThe barbiturate decreases the effect of the metabolized beta-blocker
PipobromanAntagonism
PirbuterolAntagonism
PiroxicamRisk of inhibition of renal prostaglandins
PrazosinRisk of hypotension at the beginning of therapy
PrimidoneThe barbiturate decreases the effect of metabolized beta-blocker
ProcaterolAntagonism
PropafenonePropafenone may increase the effect of beta-blocker, metoprolol.
RepaglinideThe beta-blocker, metoprolol, may decrease symptoms of hypoglycemia.
RifampicinRifampin may decrease the serum concentration of metoprolol by increasing its metabolism.
SalbutamolAntagonism
SalmeterolAntagonism
SertralineThe SSRI increases the effect of the beta-blocker
TelithromycinTelithromycin may possibly increase metoprolol effect
TerazosinIncreased risk of hypotension. Initiate concomitant therapy cautiously.
TerbinafineTerbinafine may reduce the metabolism and clearance of Metoprolol. Consider alternate therapy or monitor for therapeutic/adverse effects of Metoprolol if Terbinafine is initiated, discontinued or dose changed.
TerbutalineAntagonism
TolazamideThe beta-blocker, metoprolol, may decrease symptoms of hypoglycemia.
TolbutamideThe beta-blocker, metoprolol, may decrease symptoms of hypoglycemia.
TreprostinilAdditive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
VerapamilIncreased effect of both drugs
Food Interactions
  • Avoid alcohol.
  • Avoid natural licorice.
  • Take with food.

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. Schafer M, Frischkopf K, Taimor G, Piper HM, Schluter KD: Hypertrophic effect of selective beta(1)-adrenoceptor stimulation on ventricular cardiomyocytes from adult rat. Am J Physiol Cell Physiol. 2000 Aug;279(2):C495-503. Pubmed
  2. Staudt A, Mobini R, Fu M, Grosse Y, Stangl V, Stangl K, Thiele A, Baumann G, Felix SB: beta(1)-Adrenoceptor antibodies induce positive inotropic response in isolated cardiomyocytes. Eur J Pharmacol. 2001 Jul 6;423(2-3):115-9. Pubmed
  3. Staudt Y, Mobini R, Fu M, Felix SB, Kuhn JP, Staudt A: Beta1-adrenoceptor antibodies induce apoptosis in adult isolated cardiomyocytes. Eur J Pharmacol. 2003 Apr 11;466(1-2):1-6. Pubmed
  4. Johnson JA, Zineh I, Puckett BJ, McGorray SP, Yarandi HN, Pauly DF: Beta 1-adrenergic receptor polymorphisms and antihypertensive response to metoprolol. Clin Pharmacol Ther. 2003 Jul;74(1):44-52. Pubmed
  5. Liu J, Liu ZQ, Tan ZR, Chen XP, Wang LS, Zhou G, Zhou HH: Gly389Arg polymorphism of beta1-adrenergic receptor is associated with the cardiovascular response to metoprolol. Clin Pharmacol Ther. 2003 Oct;74(4):372-9. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. 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. Zebrack JS, Munger M, Macgregor J, Lombardi WL, Stoddard GP, Gilbert EM: Beta-receptor selectivity of carvedilol and metoprolol succinate in patients with heart failure (SELECT trial): a randomized dose-ranging trial. Pharmacotherapy. 2009 Aug;29(8):883-90. Pubmed

Enzymes

1. Cytochrome P450 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

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. Belpaire FM, Wijnant P, Temmerman A, Rasmussen BB, Brosen K: The oxidative metabolism of metoprolol in human liver microsomes: inhibition by the selective serotonin reuptake inhibitors. Eur J Clin Pharmacol. 1998 May;54(3):261-4. 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. Lexicomp

2. Cytochrome P450 2C19

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2C19 P33261 Details

References:

  1. 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

Transporters

1. Solute carrier family 22 member 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 2 O15244 Details

References:

  1. Dudley AJ, Bleasby K, Brown CD: The organic cation transporter OCT2 mediates the uptake of beta-adrenoceptor antagonists across the apical membrane of renal LLC-PK cell monolayers. Br J Pharmacol. 2000 Sep;131(1):71-9. Pubmed

2. Multidrug resistance protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

References:

  1. 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
  2. Doppenschmitt S, Langguth P, Regardh CG, Andersson TB, Hilgendorf C, Spahn-Langguth H: Characterization of binding properties to human P-glycoprotein: development of a [3H]verapamil radioligand-binding assay. J Pharmacol Exp Ther. 1999 Jan;288(1):348-57. Pubmed
  3. Neuhoff S, Ungell AL, Zamora I, Artursson P: pH-dependent bidirectional transport of weakly basic drugs across Caco-2 monolayers: implications for drug-drug interactions. Pharm Res. 2003 Aug;20(8):1141-8. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on October 08, 2013 14:24