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 stabilizing 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
Synonyms
  • (±)-esmolol
  • (±)-methyl p-(2-hydroxy-3-(isopropylamino)propoxy)hydrocinnamate
  • 3-[4-(2-Hydroxy-3-isopropylamino-propoxy)-phenyl]-propionic acid methyl ester
  • Methyl 4-(2-hydroxy-3-((1-methylethyl)amino)propoxy)benzenepropanoate
  • methyl p-(2-hydroxy-3-(isopropylamino)propoxy)hydrocinnamate
Product Ingredients
IngredientUNIICASInChI Key
Esmolol hydrochlorideV05260LC8D81161-17-3GEKNCWBANDDJJL-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
BreviblocInjection20 mg/1mLIntravenousBaxter Laboratories1986-12-31Not applicableUs
BreviblocInjection20 mg/1mLIntravenousBaxter Laboratories1986-12-31Not applicableUs
BreviblocInjection10 mg/1mLIntravenousBaxter Laboratories1986-12-31Not applicableUs
BreviblocInjection10 mg/1mLIntravenousBaxter Laboratories1986-12-31Not applicableUs
BreviblocInjection10 mg/1mLIntravenousGeneral Injectables & Vaccines2010-07-01Not applicableUs
BreviblocInjection10 mg/1mLIntravenousBaxter Laboratories1986-12-31Not applicableUs
BreviblocInjection10 mg/1mLIntravenousBaxter Laboratories1986-12-31Not applicableUs
BreviblocInjection20 mg/1mLIntravenousBaxter Laboratories1986-12-31Not applicableUs
Brevibloc Injection 10mg/mlSolution10 mgIntravenousBaxter Laboratories1996-08-16Not applicableCanada
Brevibloc Injection 250mg/mlLiquid250 mgIntravenousBaxter Laboratories1997-01-172007-06-27Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Esmolol HydrochlorideInjection, solution10 mg/1mLIntravenousBedford Pharmaceuticals2004-10-042014-09-30Us
Esmolol HydrochlorideInjection10 mg/1mLIntravenousGeneral Injectables & Vaccines2010-08-01Not applicableUs
Esmolol HydrochlorideInjection, solution10 mg/1mLIntravenousMylan Institutional2007-05-29Not applicableUs
Esmolol HydrochlorideInjection, solution10 mg/1mLIntravenousAmerican Regent2016-01-01Not applicableUs
Esmolol HydrochlorideInjection, solution10 mg/1mLIntravenousBedford Pharmaceuticals2008-03-032012-01-31Us
Esmolol HydrochlorideInjection, solution10 mg/1mLIntravenousGeneral Injectables & Vaccines2015-09-10Not applicableUs
Esmolol HydrochlorideInjection, solution10 mg/1mLIntravenousFresenius Kabi2004-11-30Not applicableUs
Esmolol HydrochlorideInjection, solution10 mg/1mLIntravenousMylan Teoranta2013-05-092013-05-10Us
Esmolol HydrochlorideInjection, solution100 mg/10mLIntravenousAuroMedics Pharma LLC2015-07-23Not applicableUs
Esmolol HydrochlorideInjection, solution100 mg/10mLIntravenousMedical Purchasing Solutions, Llc2015-07-23Not applicableUs
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
BreviblocEsmolol hydrochloride (250 mg/1mL)Injection, solution, concentrateIntravenousBaxter Healthcare Corporation2007-03-022007-03-02Us
BreviblocEsmolol hydrochloride (20 mg/1mL)InjectionIntravenousBaxter Healthcare Corporation2007-03-022007-03-02Us
Categories
UNII
MDY902UXSR
CAS number
81147-92-4
Weight
Average: 295.374
Monoisotopic: 295.178358293
Chemical Formula
C16H25NO4
InChI Key
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
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

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.

Associated Conditions
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.

TargetActionsOrganism
ABeta-1 adrenergic receptor
antagonist
Human
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
PathwayCategory
Esmolol Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
1,10-Phenanthroline1,10-Phenanthroline may increase the bradycardic activities of Esmolol.
3-isobutyl-1-methyl-7H-xanthineThe risk or severity of adverse effects can be increased when Esmolol is combined with 3-isobutyl-1-methyl-7H-xanthine.
4-MethoxyamphetamineThe therapeutic efficacy of 4-Methoxyamphetamine can be decreased when used in combination with Esmolol.
6-O-benzylguanineThe risk or severity of adverse effects can be increased when Esmolol is combined with 6-O-benzylguanine.
7-DeazaguanineThe risk or severity of adverse effects can be increased when Esmolol is combined with 7-Deazaguanine.
7,9-DimethylguanineThe risk or severity of adverse effects can be increased when Esmolol is combined with 7,9-Dimethylguanine.
8-azaguanineThe risk or severity of adverse effects can be increased when Esmolol is combined with 8-azaguanine.
8-chlorotheophyllineThe risk or severity of adverse effects can be increased when Esmolol is combined with 8-chlorotheophylline.
9-DeazaguanineThe risk or severity of adverse effects can be increased when Esmolol is combined with 9-Deazaguanine.
9-MethylguanineThe risk or severity of adverse effects can be increased when Esmolol is combined with 9-Methylguanine.
Food Interactions
Not Available

References

Synthesis Reference
US4593119
General References
Not Available
External Links
Human Metabolome Database
HMDB0014333
KEGG Drug
D07916
KEGG Compound
C06980
PubChem Compound
59768
PubChem Substance
46506146
ChemSpider
53916
BindingDB
50404796
ChEBI
88206
ChEMBL
CHEMBL768
Therapeutic Targets Database
DAP000304
PharmGKB
PA449500
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Esmolol
ATC Codes
C07AB09 — Esmolol
AHFS Codes
  • 24:24.00 — Beta-adrenergic Blocking Agents
MSDS
Download (56.3 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentHealthy Volunteers3
1CompletedTreatmentNeoplasms, Brain1
1, 2Active Not RecruitingTreatmentDiabetic Foot Ulcers (DFU)1
1, 2CompletedSupportive CareOvarian Cysts1
1, 2WithdrawnTreatmentDysautonomia / Traumatic Brain Injury (TBI)1
1, 2WithdrawnTreatmentMyocardial Reperfusion Injury1
2CompletedTreatmentChronic Rhinosinusitis1
2CompletedTreatmentHealthy Volunteers / Pharmacokinetics/Dynamics Study1
2CompletedTreatmentNonvalvular Atrial Fibrillation1
2CompletedTreatmentShock, Septic2
2RecruitingTreatmentArterial Hypotension / Shock, Septic / Tachycardia1
2RecruitingTreatmentBloodpressure / Heart Rate1
2RecruitingTreatmentShock, Septic3
2Unknown StatusTreatmentAgeing / Cardiovascular Disease (CVD) / Trauma, Multiple1
2, 3RecruitingTreatmentShock, Septic1
3CompletedTreatmentCerebral Aneurysms / Cerebral Arterial Diseases1
3CompletedTreatmentCoronary Artery Disease1
3RecruitingTreatmentIntracranial Aneurysms / Neoplasms, Intracranial1
3TerminatedTreatmentAnaesthesia therapy1
3TerminatedTreatmentHigh-risk, Non-cardiovascular Surgeries1
4CompletedPreventionPostoperative pain1
4CompletedPreventionSurgery, Laparoscopic1
4CompletedTreatmentAnesthesia; Adverse Effect / Reflex, Abnormal / Tinnitus, Spontaneous Oto-Acoustic Emission1
4CompletedTreatmentGall Stone Disease1
4CompletedTreatmentHigh Blood Pressure (Hypertension) / Myocardial Ischemia / Tachycardia1
4Not Yet RecruitingScreeningCerebral Oxygen Saturation / Hypotension Drug-Induced1
4Not Yet RecruitingTreatmentShock, Cardiogenic1
4RecruitingBasic ScienceDrug Overdose / Overdose of Beta-adrenergic Blocking Drug1
4RecruitingPreventionHemodynamics Instability1
4RecruitingPreventionIntubations1
4RecruitingPreventionSurgery, Cardiac1
4TerminatedNot AvailableLaminectomy1
4TerminatedPreventionNausea / Occasional Constipation / Pain / Vomiting1
4TerminatedTreatmentAnginal Pain / Cardiac Diseases / High Blood Pressure (Hypertension) / Vascular Diseases1
4Unknown StatusNot AvailableDeviation Septum Nasal1
4Unknown StatusSupportive CareInjection Site Irritation1
4Unknown StatusTreatmentAcute Coronary Syndromes (ACS) / Coronary Artery Disease1
Not AvailableActive Not RecruitingPreventionCancer, Breast / Postoperative pain / Prophylaxis against postoperative nausea and vomiting1
Not AvailableCompletedNot AvailableHigh Blood Pressure (Hypertension)1
Not AvailableCompletedNot AvailableShock, Septic / Tachycardia1
Not AvailableCompletedPreventionPain2
Not AvailableCompletedTreatmentCVA (Cerebrovascular Accident) / Intracerebral Hemorrhage / Intracranial Hemorrhages1
Not AvailableCompletedTreatmentHigh Blood Pressure (Hypertension)1
Not AvailableCompletedTreatmentPain1
Not AvailableCompletedTreatmentSevere Sepsis1
Not AvailableRecruitingTreatmentScheduled Laparoscopic Surgery1
Not AvailableUnknown StatusNot AvailableMyocardial Ischemia1
Not AvailableUnknown StatusBasic ScienceDecrease in Heart Rate Below Baseline Value1
Not AvailableWithdrawnTreatmentSubarachnoid Hemorrhage1

Pharmacoeconomics

Manufacturers
  • Baxter healthcare corp anesthesia critical care
  • App pharmaceuticals llc
  • Bedford laboratories
  • Bioniche pharma usa llc
Packagers
  • APP Pharmaceuticals
  • Baxter International Inc.
  • Bedford Labs
  • Ben Venue Laboratories Inc.
  • Bioniche Pharma
  • Bristol-Myers Squibb Co.
  • Draxis Specialty Pharmaceuticals Inc.
  • General Injectables and Vaccines Inc.
  • Paddock Labs
Dosage forms
FormRouteStrength
InjectionIntravenous20 mg/1mL
Injection, solution, concentrateIntravenous250 mg/1mL
SolutionIntravenous10 mg
LiquidIntravenous10 mg
LiquidIntravenous250 mg
InjectionIntravenous10 mg/1mL
Injection, solutionIntravenous10 mg/1mL
Injection, solutionIntravenous100 mg/10mL
Prices
Unit descriptionCostUnit
Brevibloc 250 mg/ml ampul13.21USD ml
Brevibloc 10 mg/ml vial2.21USD ml
Brevibloc 20 mg/ml iv bag1.54USD ml
Esmolol hcl 10 mg/ml vial1.26USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2410446No2008-08-262022-01-02Canada
US6528540Yes2001-07-122021-07-12Us
US6310094Yes2001-07-122021-07-12Us
US8835505No2013-03-152033-03-15Us
US8829054No2013-03-152033-03-15Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityVery soluble as hydrochloride saltNot Available
logP1.7Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.144 mg/mLALOGPS
logP2.02ALOGPS
logP1.82ChemAxon
logS-3.3ALOGPS
pKa (Strongest Acidic)14.09ChemAxon
pKa (Strongest Basic)9.67ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area67.79 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity81.05 m3·mol-1ChemAxon
Polarizability33.68 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.7023
Blood Brain Barrier-0.9645
Caco-2 permeable+0.5
P-glycoprotein substrateSubstrate0.6511
P-glycoprotein inhibitor INon-inhibitor0.8625
P-glycoprotein inhibitor IINon-inhibitor0.7171
Renal organic cation transporterNon-inhibitor0.8605
CYP450 2C9 substrateNon-substrate0.8124
CYP450 2D6 substrateSubstrate0.663
CYP450 3A4 substrateNon-substrate0.5869
CYP450 1A2 substrateNon-inhibitor0.864
CYP450 2C9 inhibitorNon-inhibitor0.8789
CYP450 2D6 inhibitorNon-inhibitor0.8806
CYP450 2C19 inhibitorNon-inhibitor0.9585
CYP450 3A4 inhibitorNon-inhibitor0.8495
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9761
Ames testNon AMES toxic0.9066
CarcinogenicityNon-carcinogens0.9519
BiodegradationNot ready biodegradable0.6493
Rat acute toxicity1.9194 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9556
hERG inhibition (predictor II)Non-inhibitor0.774
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0002-0490000000-55cd388bbf570d69d195

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenol ethers. These are aromatic compounds containing an ether group substituted with a benzene ring.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Phenol ethers
Sub Class
Not Available
Direct Parent
Phenol ethers
Alternative Parents
Phenoxy compounds / Fatty acid esters / Alkyl aryl ethers / Methyl esters / Secondary alcohols / Amino acids and derivatives / 1,2-aminoalcohols / Monocarboxylic acids and derivatives / Dialkylamines / Organopnictogen compounds
show 3 more
Substituents
Phenoxy compound / Phenol ether / Alkyl aryl ether / Fatty acid ester / Monocyclic benzene moiety / Fatty acyl / Methyl ester / 1,2-aminoalcohol / Secondary alcohol / Amino acid or derivatives
show 17 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
aromatic ether, secondary alcohol, secondary amino compound, methyl ester, ethanolamines (CHEBI:4856)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Receptor signaling protein activity
Specific Function
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 e...
Gene Name
ADRB1
Uniprot ID
P08588
Uniprot Name
Beta-1 adrenergic receptor
Molecular Weight
51322.1 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  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:7612051]
  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:7957532]
  4. Kirshenbaum JM: Nonthrombolytic intervention in acute myocardial infarction. Am J Cardiol. 1989 Jul 18;64(4):25B-28B. [PubMed:2568748]
  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:2894187]
  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:1975995]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
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...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Sternieri E, Coccia CP, Pinetti D, Guerzoni S, Ferrari A: Pharmacokinetics and interactions of headache medications, part II: prophylactic treatments. Expert Opin Drug Metab Toxicol. 2006 Dec;2(6):981-1007. doi: 10.1517/17425255.2.6.981 . [PubMed:17125412]
  2. Brodde OE, Kroemer HK: Drug-drug interactions of beta-adrenoceptor blockers. Arzneimittelforschung. 2003;53(12):814-22. [PubMed:14732961]
  3. Iwaki M, Niwa T, Bandoh S, Itoh M, Hirose H, Kawase A, Komura H: Application of substrate depletion assay to evaluation of CYP isoforms responsible for stereoselective metabolism of carvedilol. Drug Metab Pharmacokinet. 2016 Dec;31(6):425-432. doi: 10.1016/j.dmpk.2016.08.007. Epub 2016 Sep 2. [PubMed:27836712]

Drug created on June 13, 2005 07:24 / Updated on September 23, 2018 19:37