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Identification
Name Esmolol
Accession Number DB00187 (APRD00954)
Type small molecule
Groups approved
Description

Esmolol (trade name Brevibloc) is a cardioselective beta1 receptor blocker with rapid onset, a very short duration of action, and no significant intrinsic sympathomimetic or membrane stabilising activity at therapeutic dosages.

Esmolol decreases the force and rate of heart contractions by blocking beta-adrenergic receptors of the sympathetic nervous system, which are found in the heart and other organs of the body. Esmolol prevents the action of two naturally occurring substances: epinephrine and norepinephrine.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Brand names
  • Brevibloc
  • Esmolol HCL
  • Esmolol Hydrochloride
Brand name mixtures Not Available
Categories
  • Adrenergic beta-Antagonists
CAS number 103598-03-4
Weight Average: 295.374
Monoisotopic: 295.178358293
Chemical Formula C16H25NO4
InChI Key InChIKey=AQNDDEOPVVGCPG-UHFFFAOYSA-N
InChI
InChI=1S/C16H25NO4/c1-12(2)17-10-14(18)11-21-15-7-4-13(5-8-15)6-9-16(19)20-3/h4-5,7-8,12,14,17-18H,6,9-11H2,1-3H3
Plain Text
IUPAC Name
methyl 3-(4-{2-hydroxy-3-[(propan-2-yl)amino]propoxy}phenyl)propanoate
SMILES
COC(=O)CCC1=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
  • Carboxylic Acids and Derivatives
  • Hydroxy Compounds
  • Acetates
  • 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 rapid control of ventricular rate in patients with atrial fibrillation or atrial flutter in perioperative, postoperative, or other emergent circumstances where short term control of ventricular rate with a short-acting agent is desirable. Also used in noncompensatory sinus tachycardia where the rapid heart rate requires specific intervention.
Pharmacodynamics Not Available
Mechanism of action Similar to other beta-blockers, esmolol blocks the agonistic effect of the sympathetic neurotransmitters by competing for receptor binding sites. Because it predominantly blocks the beta-1 receptors in cardiac tissue, it is said to be cardioselective. In general, so-called cardioselective beta-blockers are relatively cardioselective; at lower doses they block beta-1 receptors only but begin to block beta-2 receptors as the dose increases. At therapeutic dosages, esmolol does not have intrinsic sympathomimetic activity (ISA) or membrane-stabilizing (quinidine-like) activity. Antiarrhythmic activity is due to blockade of adrenergic stimulation of cardiac pacemaker potentials. In the Vaughan Williams classification of antiarrhythmics, beta-blockers are considered to be class II agents.
Absorption Rapidly absorbed, steady-state blood levels for dosages from 50-300 µg/kg/min (0.05-0.3 mg/kg/mm) are obtained within five minutes.
Volume of distribution Not Available
Protein binding 55% bound to human plasma protein, while the acid metabolite is 10% bound.
Metabolism

Rapidly metabolized by hydrolysis of the ester linkage, chiefly by the esterases in the cytosol of red blood cells and not by plasma cholinesterases or red cell membrane acetylcholinesterase. Mainly in red blood cells to a free acid metabolite (with 1/1500 the activity of esmolol) and methanol.
Route of elimination Consistent with the high rate of blood-based metabolism of esmolol hydrochloride, less than 2% of the drug is excreted unchanged in the urine. The acid metabolite has an elimination half-life of about 3.7 hours and is excreted in the urine with a clearance approximately equivalent to the glomerular filtration rate. Excretion of the acid metabolite is significantly decreased in patients with renal disease, with the elimination half-life increased to about ten-fold that of normals, and plasma levels considerably elevated.
Half life Rapid distribution half-life of about 2 minutes and an elimination half-life of about 9 minutes. The acid metabolite has an elimination half-life of about 3.7 hours.
Clearance
  • 20 L/kg/hr [Men]
Toxicity Symptoms of overdose include cardiac arrest, bradycardia, hypotension, electromechanical dissociation and loss of consciousness.
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00301 Esmolol Pathway SMP00301
Pharmacoeconomics
Manufacturers
  • Baxter healthcare corp anesthesia critical care
  • App pharmaceuticals llc
  • Bedford laboratories
  • Bioniche pharma usa llc
Packagers
Dosage forms
Form Route Strength
Liquid Intravenous
Prices
Unit description Cost Unit
Brevibloc 250 mg/ml ampul 13.21 USD ml
Brevibloc 10 mg/ml vial 2.21 USD ml
Brevibloc 20 mg/ml iv bag 1.54 USD ml
Esmolol hcl 10 mg/ml vial 1.26 USD ml
Patents
Country Patent Number Approved Expires
United States 6310094 2001-07-12 2021-07-12
Canada 2410446 2008-08-26 2022-01-02
Properties
State solid
Melting point Not Available
Experimental Properties
Property Value Source
water solubility Very soluble as hydrochloride salt PhysProp
logP 1.7 PhysProp
Predicted Properties
Property Value Source
water solubility 1.44e-01 g/l ALOGPS
logP 2.02 ALOGPS
logP 1.82 ChemAxon Molconvert
logS -3.31 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 4 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 67.79 ChemAxon Molconvert
rotatable bond count 10 ChemAxon Molconvert
refractivity 81.05 ChemAxon Molconvert
polarizability 33.68 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Compound C06980 Link_out
PubChem Compound 59768 Link_out
PubChem Substance 46506146 Link_out
ChemSpider 53916 Link_out
ChEBI 4856 Link_out
ChEMBL 4856 Link_out
Therapeutic Targets Database DAP000304 Link_out
PharmGKB PA449500 Link_out
Drug Product Database 2188864 Link_out
RxList http://www.rxlist.com/cgi/generic3/esmolol.htm Link_out
Drugs.com http://www.drugs.com/cdi/esmolol.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Esmolol Link_out
ATC Codes
  • C07AB09
AHFS Codes
  • 24:24.00
PDB Entries Not Available
FDA label Not Available
MSDS show (56.3 KB)
Interactions
Drug Interactions Not Available
Food Interactions Not Available
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. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Jahn P, Eckrich B, Schneidrowski B, Volz-Zang C, Schulte B, Mutschler E, Palm D: Beta 1-adrenoceptor subtype selective antagonism of esmolol and its major metabolite in vitro and in man. Investigations using tricresylphosphate as red blood cell carboxylesterase inhibitor. Arzneimittelforschung. 1995 May;45(5):536-41. Pubmed
  3. Volz-Zang C, Eckrich B, Jahn P, Schneidrowski B, Schulte B, Palm D: Esmolol, an ultrashort-acting, selective beta 1-adrenoceptor antagonist: pharmacodynamic and pharmacokinetic properties. Eur J Clin Pharmacol. 1994;46(5):399-404. Pubmed
  4. Kirshenbaum JM: Nonthrombolytic intervention in acute myocardial infarction. Am J Cardiol. 1989 Jul 18;64(4):25B-28B. Pubmed
  5. Jacobs JR, Maier GW, Rankin JS, Reves JG: Esmolol and left ventricular function in the awake dog. Anesthesiology. 1988 Mar;68(3):373-8. Pubmed
  6. Howie MB, Black HA, Zvara D, McSweeney TD, Martin DJ, Coffman JA: Esmolol reduces autonomic hypersensitivity and length of seizures induced by electroconvulsive therapy. Anesth Analg. 1990 Oct;71(4):384-8. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:01

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