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Identification
Name Metoprolol
Accession Number DB00264 (APRD00208)
Type small molecule
Groups approved
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 β-1-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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Metoprolol succinate
  • Metoprolol Tartrate
Brand names
  • Beloc
  • Betaloc
  • Lopresor
  • Lopresoretic
  • Lopressor
  • Lopressor HCT
  • Metroprolol
  • Prelis
  • Selo-Zok
  • Seloken
  • Selopral
  • Toprol
  • Toprol XL
  • Toprol-XL
Brand name mixtures Not Available
Categories
  • Antihypertensive Agents
  • Adrenergic Agents
  • Adrenergic beta-Antagonists
  • Sympatholytics
  • Antiarrhythmic Agents
  • Anti-Arrhythmia Agents
CAS number 37350-58-6
Weight Average: 267.3639
Monoisotopic: 267.183443671
Chemical Formula C15H25NO3
InChI Key InChIKey=IUBSYMUCCVWXPE-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
Plain Text
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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Phenols and Derivatives
  • Ethers
  • Anisoles
  • Phenyl Esters
Substructures
  • Hydroxy Compounds
  • Aliphatic and Aryl Amines
  • Phenols and Derivatives
  • Ethers
  • Benzene and Derivatives
  • Amino Alcohols
  • Aromatic compounds
  • Anisoles
  • Alcohols and Polyols
  • Phenyl Esters
Pharmacology
Indication For 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.
Pharmacodynamics Metoprolol, 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 action Metoprolol 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.
Absorption Rapid and complete, 50%
Volume of distribution Not Available
Protein binding 12%
Metabolism

Primarily hepatic

Enzyme Metabolite Reaction Km Vmax
Cytochrome P450 2D6 alpha-Hydroxymetoprolol hydroxylation 70 0.039
Route of elimination Less 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 life 3-7 hours
Clearance Not Available
Toxicity LD50=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
Pathways
Pathway Name SMPDB ID
Smp00302 Metoprolol Pathway SMP00302
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
Form Route Strength
Liquid Intravenous
Solution Intravenous
Tablet Oral
Tablet, extended release Oral
Prices
Unit description Cost Unit
Metoprolol tartrate powder 5.51 USD g
Lopressor 5 mg/5 ml ampul 3.85 USD ml
Lopressor hct 100-25 tablet 3.21 USD tablet
Toprol XL 200 mg 24 Hour tablet 3.08 USD tablet
Lopressor HCT 100-50 mg tablet 3.06 USD tablet
Toprol xl 200 mg tablet 2.96 USD tablet
Lopressor hct 100-50 tablet 2.82 USD tablet
Lopressor 100 mg tablet 2.75 USD tablet
Metoprolol Succinate 200 mg 24 Hour tablet 2.62 USD tablet
Metoprolol succ er 200 mg tablet 2.29 USD tablet
Lopressor HCT 100-25 mg tablet 2.21 USD tablet
Lopressor HCT 50-25 mg tablet 2.14 USD tablet
Lopressor hct 50-25 tablet 2.06 USD tablet
Toprol XL 100 mg 24 Hour tablet 1.93 USD tablet
Toprol xl 100 mg tablet 1.86 USD tablet
Lopressor 50 mg tablet 1.81 USD tablet
Metoprolol Succinate 100 mg 24 Hour tablet 1.53 USD tablet
Metoprolol succ er 100 mg tablet 1.44 USD tablet
Toprol XL 25 mg 24 Hour tablet 1.43 USD tablet
Toprol XL 50 mg 24 Hour tablet 1.43 USD tablet
Lopresor 1 mg/ml 1.29 USD ml
Toprol xl 25 mg tablet 1.24 USD tablet
Toprol xl 50 mg tablet 1.24 USD tablet
Metoprolol Succinate 25 mg 24 Hour tablet 1.17 USD tablet
Metoprolol Succinate 50 mg 24 Hour tablet 1.13 USD tablet
Metoprolol succ er 50 mg tablet 0.9 USD tablet
Metoprolol succ er 25 mg tablet 0.87 USD tablet
Metoprolol tartrate 100 mg tablet 0.8 USD tablet
Toprol xl 100 mg tablet sa 0.8 USD tablet
Lopresor 100 mg Tablet 0.61 USD tablet
Lopresor Sr 200 mg Sustained-Release Tablet 0.61 USD tablet
Metoprolol tartrate 50 mg tablet 0.56 USD tablet
Metoprolol tartrate 25 mg tablet 0.34 USD tablet
Apo-Metoprolol Sr 200 mg Sustained-Release Tablet 0.34 USD tablet
Lopresor Sr 100 mg Sustained-Release Tablet 0.34 USD tablet
Sandoz Metoprolol Sr 200 mg Sustained-Release Tablet 0.34 USD tablet
Lopresor 50 mg Tablet 0.3 USD tablet
Apo-Metoprolol (Type L) 100 mg Tablet 0.23 USD tablet
Apo-Metoprolol 100 mg Tablet 0.23 USD tablet
Mylan-Metoprolol (Type L) 100 mg Tablet 0.23 USD tablet
Novo-Metoprol (Fc) 100 mg Tablet 0.23 USD tablet
Novo-Metoprol 100 mg Tablet 0.23 USD tablet
Nu-Metop 100 mg Tablet 0.23 USD tablet
Pms-Metoprolol-L 100 mg Tablet 0.23 USD tablet
Sandoz Metoprolol (Type L) 100 mg Tablet 0.23 USD tablet
Apo-Metoprolol Sr 100 mg Sustained-Release Tablet 0.19 USD tablet
Sandoz Metoprolol Sr 100 mg Sustained-Release Tablet 0.19 USD tablet
Apo-Metoprolol (Type L) 50 mg Tablet 0.13 USD tablet
Apo-Metoprolol 50 mg Tablet 0.13 USD tablet
Mylan-Metoprolol (Type L) 50 mg Tablet 0.13 USD tablet
Novo-Metoprol (Fc) 50 mg Tablet 0.13 USD tablet
Novo-Metoprol 50 mg Tablet 0.13 USD tablet
Nu-Metop 50 mg Tablet 0.13 USD tablet
Pms-Metoprolol-L 50 mg Tablet 0.13 USD tablet
Sandoz Metoprolol (Type L) 50 mg Tablet 0.13 USD tablet
Apo-Metoprolol 25 mg Tablet 0.07 USD tablet
Pms-Metoprolol-L 25 mg Tablet 0.07 USD tablet
Patents Not Available
Properties
State solid
Melting point 120 oC (tartarate salt)
Experimental Properties
Property Value Source
water solubility 16.9 mg/mL PhysProp
logP 1.6 PhysProp
Caco2 permeability -4.59 [ADME Research, USCD] BiGG
Predicted Properties
Property Value Source
water solubility 4.02e-01 g/l ALOGPS
logP 1.80 ALOGPS
logP 1.76 ChemAxon Molconvert
logS -2.82 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 4 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 50.72 ChemAxon Molconvert
rotatable bond count 9 ChemAxon Molconvert
refractivity 76.70 ChemAxon Molconvert
polarizability 31.90 ChemAxon Molconvert
References
Synthesis Reference Not Available
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
Resource Link
KEGG Drug D02358 Link_out
KEGG Compound C07202 Link_out
PubChem Compound 4171 Link_out
PubChem Substance 46506211 Link_out
ChemSpider 4027 Link_out
BindingDB 25756 Link_out
ChEBI 6904 Link_out
ChEMBL 6904 Link_out
Therapeutic Targets Database DAP000481 Link_out
Drug Product Database 2253518 Link_out
RxList http://www.rxlist.com/cgi/generic/metopxl.htm Link_out
Drugs.com http://www.drugs.com/metoprolol.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Metoprolol Link_out
ATC Codes
  • C07AB02
  • C07AB52
AHFS Codes
  • 24:24.00
PDB Entries Not Available
FDA label show (439 KB)
MSDS show (73.9 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Avoid alcohol.
  • Avoid natural licorice.
  • Take with food.
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. 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

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. 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

Actions: substrate, inhibitor

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. 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

2. Cytochrome P450 2C19

Actions: substrate

Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine

UniProt ID: P33261 Link_out
Gene: CYP2C19 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: inhibitor

Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creatinine, amantadine, memantine, acriflavine, 4-[4-(dimethylamino)-styryl]-N-methylpyridinium ASP, amiloride, metformin, N-1-methylnicotinamide (NMN), tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, cisplatin and oxaliplatin. Cisplatin may develop a nephrotoxic action. Transport of creatinine is inhibited by fluoroquinolones such as DX-619 and LVFX. This transporter is a major determinant of the anticancer activity of oxaliplatin and may contribute to antitumor specificity

UniProt ID: O15244 Link_out
Gene: SLC22A2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate, 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. 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
Comments
Drug created on June 13, 2005 07:24 / Updated on September 29, 2011 14:56

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.