| Version |
2.5 |
| Creation Date |
2005-06-13 13:24:05 |
| Update Date |
2009-04-16 16:47:30 |
| Primary Accession Number |
DB00187 |
| Secondary Accession Number |
|
| Name |
Esmolol |
| Drug Type |
|
| 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. |
| Synonyms |
Not Available |
| Brand Names |
- Brevibloc
- Esmolol HCL
- Esmolol Hydrochloride
|
| Brand Mixtures |
Not Available |
| Chemical IUPAC Name |
methyl 3-[4-[2-hydroxy-3-(propan-2-ylamino)propoxy]phenyl]propanoate |
| Chemical Formula |
C16H25NO4 |
| Chemical Structure |
 |
| CAS Registry Number |
103598-03-4 |
| InChI Identifier |
InChI=1/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 |
| InChI Key |
AQNDDEOPVVGCPG-UHFFFAOYAE |
| KEGG Drug |
Not Available |
| KEGG Compound |
C06980  |
| PubChem Compound |
59768 |
| PubChem Substance |
9194 |
| ChEBI ID |
Not Available |
| PharmGKB ID |
PA449500 |
| HET ID |
Not Available |
| GenBank ID |
Not Available |
| Drug ID Number [DIN] |
02188864 |
| RxList Link |
http://www.rxlist.com/cgi/generic3/esmolol.htm |
| PDRhealth Link |
Not Available |
| Wikipedia Link |
http://en.wikipedia.org/wiki/Esmolol |
| FDA Label |
Not Available |
| Material Safety Data Sheet (MSDS) |
|
| Synthesis Reference |
Not Available |
| Average Molecular Weight |
295.3740 |
| Monoisotopic Molecular Weight |
295.1784 |
| State |
Solid |
| Melting Point |
Not Available |
| Experimental Water Solubility |
Very soluble as hydrochloride salt
Source: PhysProp
|
| Predicted Water Solubility |
1.44e-01 mg/mL
Calculated using ALOGPS
|
| Experimental LogP/Hydrophobicity |
1.7
Source: PhysProp
|
| Predicted LogP |
2.02
Calculated using ALOGPS
|
| Experimental LogS |
Not Available |
| Predicted LogS |
-3.31
Calculated using ALOGPS
|
| Experimental Caco2 Permeability |
Not Available |
| pKa/Isoelectric Point |
Not Available |
| Mass Spectrum |
Not Available
|
| MOL File |
Show | Download |
| SDF File |
Show | Download |
| PDB File |
Show | Download |
| 2D Structure |
|
| 3D Structure |
|
| Experimental PDB ID |
Not Available |
| Isomeric SMILES |
COC(=O)CCC1=CC=C(OC[C@H](O)CNC(C)C)C=C1 |
| Canonical SMILES |
COC(=O)CCC1=CC=C(OCC(O)CNC(C)C)C=C1 |
| Drug Category |
- Adrenergic beta-Antagonists
|
| ATC Codes |
|
| AHFS Codes |
|
| 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. |
| Pharmacology |
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. |
| Toxicity |
Symptoms of overdose include cardiac arrest, bradycardia, hypotension, electromechanical dissociation and loss of consciousness. |
| Protein Binding |
55% bound to human plasma protein, while the acid metabolite is 10% bound. |
| Biotransformation |
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. |
| 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. |
| Dosage Forms |
| Form |
Route |
| Liquid |
Intravenous |
|
| Patient Information |
Not Available |
| Contraindications |
Show |
| Interactions |
Show |
| Drug Interactions |
| Drug |
Interaction |
| Acetohexamide |
The beta-blocker decreases the symptoms of hypoglycemia |
| Chlorpropamide |
The beta-blocker decreases the symptoms of hypoglycemia |
| Clonidine |
Increased hypertension when clonidine stopped |
| Dihydroergotamine |
Ischemia with risk of gangrene |
| Dihydroergotoxine |
Ischemia with risk of gangrene |
| Disopyramide |
The beta-blocker increases toxicity of disopyramide |
| Epinephrine |
Hypertension, then bradycardia |
| Ergonovine |
Ischemia with risk of gangrene |
| Ergotamine |
Ischemia with risk of gangrene |
| Fenoterol |
Antagonism |
| Formoterol |
Antagonism |
| Glibenclamide |
The beta-blocker decreases the symptoms of hypoglycemia |
| Gliclazide |
The beta-blocker decreases the symptoms of hypoglycemia |
| Glipizide |
The beta-blocker decreases the symptoms of hypoglycemia |
| Glisoxepide |
The beta-blocker decreases the symptoms of hypoglycemia |
| Glycodiazine |
The beta-blocker decreases the symptoms of hypoglycemia |
| Ibuprofen |
Risk of inhibition of renal prostaglandins |
| Indomethacin |
Risk of inhibition of renal prostaglandins |
| Insulin |
The beta-blocker decreases the symptoms of hypoglycemia |
| Insulin-aspart |
The beta-blocker decreases the symptoms of hypoglycemia |
| Insulin-detemir |
The beta-blocker decreases the symptoms of hypoglycemia |
| Insulin-glargine |
The beta-blocker decreases the symptoms of hypoglycemia |
| Insulin-glulisine |
The beta-blocker decreases the symptoms of hypoglycemia |
| Insulin-lispro |
The beta-blocker decreases the symptoms of hypoglycemia |
| Isoproterenol |
Antagonism |
| Lidocaine |
The beta-blocker increases the effect and toxicity of lidocaine |
| Methysergide |
Ischemia with risk of gangrene |
| Orciprenaline |
Antagonism |
| Pirbuterol |
Antagonism |
| Piroxicam |
Risk of inhibition of renal prostaglandins |
| Prazosin |
Risk of hypotension at the beginning of therapy |
| Procaterol |
Antagonism |
| Repaglinide |
The beta-blocker decreases the symptoms of hypoglycemia |
| Salbutamol |
Antagonism |
| Salmeterol |
Antagonism |
| Terbutaline |
Antagonism |
| Tolazamide |
The beta-blocker decreases the symptoms of hypoglycemia |
| Tolbutamide |
The beta-blocker decreases the symptoms of hypoglycemia |
| Verapamil |
Increased effect of both drugs |
|
| Food Interactions |
Not Available
|
| Pathways |
| Name |
SMPDB Link |
KEGG Link |
| Esmolol Pathway |
SMP00301 |
|
|
| General References |
- Wikipedia
- RxList
|
| Organisms Affected |
|
| Targets |
- Beta-1 adrenergic receptor
|
|
Drug Target 1
[top]
|
| Target 1 ID |
193 |
| Target 1 Name |
Beta-1 adrenergic receptor |
| Target 1 Synonyms |
- Beta-1 adrenoceptor
- Beta-1 adrenoreceptor
|
| Target 1 Gene Name |
ADRB1 |
| Target 1 Protein Sequence |
>Beta-1 adrenergic receptor
MGAGVLVLGASEPGNLSSAAPLPDGAATAARLLVPASPPASLLPPASESPEPLSQQWTAG
MGLLMALIVLLIVAGNVLVIVAIAKTPRLQTLTNLFIMSLASADLVMGLLVVPFGATIVV
WGRWEYGSFFCELWTSVDVLCVTASIETLCVIALDRYLAITSPFRYQSLLTRARARGLVC
TVWAISALVSFLPILMHWWRAESDEARRCYNDPKCCDFVTNRAYAIASSVVSFYVPLCIM
AFVYLRVFREAQKQVKKIDSCERRFLGGPARPPSPSPSPVPAPAPPPGPPRPAAAAATAP
LANGRAGKRRPSRLVALREQKALKTLGIIMGVFTLCWLPFFLANVVKAFHRELVPDRLFV
FFNWLGYANSAFNPIIYCRSPDFRKAFQRLLCCARRAARRRHATHGDRPRASGCLARPGP
PPSPGAASDDDDDDVVGATPPARLLEPWAGCNGGAAADSDSSLDEPCRPGFASESKV
|
| Target 1 Number of Residues |
484 |
| Target 1 Molecular Weight |
51323 |
| Target 1 Theoretical pI |
9.03 |
| Target 1 GO Classification |
|
Function
|
signal transducer activity
receptor activity
transmembrane receptor activity
G-protein coupled receptor activity
rhodopsin-like receptor activity
amine receptor activity
adrenoceptor activity
beta-adrenergic receptor activity
beta1-adrenergic receptor activity |
|
Process
|
cellular process
cell communication
signal transduction
cell surface receptor linked signal transduction
G-protein coupled receptor protein signaling pathway |
|
Component
|
cell
membrane
intrinsic to membrane
integral to membrane |
|
| Target 1 General Function |
Involved in beta1-adrenergic receptor activity |
| Target 1 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 equal affinity |
| Target 1 Pathways |
Not Available
|
| Target 1 Reactions |
Not Available |
| Target 1 Pfam Domain Function |
|
| Target 1 Signals |
|
| Target 1 Transmembrane Regions |
- 60-83
- 97-120
- 132-155
- 176-199
- 222-245
- 326-349
- 357-380
|
| Target 1 Essentiality |
Non-Essential |
| Target 1 GenBank ID Protein |
178200 |
| Target 1 UniProtKB/Swiss-Prot ID |
P08588 |
| Target 1 UniProtKB/Swiss-Prot Entry Name |
ADRB1_HUMAN |
| Target 1 PDB ID |
Not Available |
| Target 1 Cellular Location |
- Cell membrane
- multi-pass membrane protein. Localized at the plasma membrane. Found in the Golgi upo
|
| Target 1 Gene Sequence |
>1434 bp
ATGGGCGCGGGGGTGCTCGTCCTGGGCGCCTCCGAGCCCGGTAACCTGTCGTCGGCCGCA
CCGCTCCCCGACGGCGCGGCCACCGCGGCGCGGCTGCTGGTGCCCGCGTCGCCGCCCGCC
TCGTTGCTGCCTCCCGCCAGCGAAAGCCCCGAGCCGCTGTCTCAGCAGTGGACAGCGGGC
ATGGGTCTGCTGATGGCGCTCATCGTGCTGCTCATCGTGGCGGGCAATGTGCTGGTGATC
GTGGCCATCGCCAAGACGCCGCGGCTGCAGACGCTCACCAACCTCTTCATCATGTCCCTG
GCCAGCGCCGACCTGGTCATGGGGCTGCTGGTGGTGCCGTTCGGGGCCACCATCGTGGTG
TGGGGCCGCTGGGAGTACGGCTCCTTCTTCTGCGAGCTGTGGACCTCAGTGGACGTGCTG
TGCGTGACGGCCAGCATCGAGACCCTGTGTGTCATTGCCCTGGACCGCTACCTCGCCATC
ACCTCGCCCTTCCGCTACCAGAGCCTGCTGACGCGCGCGCGGGCGCGGGGCCTCGTGTGC
ACCGTGTGGGCCATCTCGGCCCTGGTGTCCTTCCTGCCCATCCTCATGCACTGGTGGCGG
GCGGAGAGCGACGAGGCGCGCCGCTGCTACAACGACCCCAAGTGCTGCGACTTCGTCACC
AACCGGGCCTACGCCATCGCCTCGTCCGTAGTCTCCTTCTACGTGCCCCTGTGCATCATG
GCCTTCGTGTACCTGCGGGTGTTCCGCGAGGCCCAGAAGCAGGTGAAGAAGATCGACAGC
TGCGAGCGCCGTTTCCTCGGCGGCCCAGCGCGGCCGCCCTCGCCCTCGCCCTCGCCCGTC
CCCGCGCCCGCGCCGCCGCCCGGACCCCCGCGCCCCGCCGCCGCCGCCGCCACCGCCCCG
CTGGCCAACGGGCGTGCGGGTAAGCGGCGGCCCTCGCGCCTCGTGGCCCTACGCGAGCAG
AAGGCGCTCAAGACGCTGGGCATCATCATGGGCGTCTTCACGCTCTGCTGGCTGCCCTTC
TTCCTGGCCAACGTGGTGAAGGCCTTCCACCGCGAGCTGGTGCCCGACCGCCTCTTCGTC
TTCTTCAACTGGCTGGGCTACGCCAACTCGGCCTTCAACCCCATCATCTACTGCCGCAGC
CCCGACTTCCGCAAGGCCTTCCAGGGACTGCTCTGCTGCGCGCGCAGGGCTGCCCGCCGG
CGCCACGCGACCCACGGAGACCGGCCGCGCGCCTCGGGCTGTCTGGCCCGGCCCGGACCC
CCGCCATCGCCCGGGGCCGCCTCGGACGACGACGACGACGATGTCGTCGGGGCCACGCCG
CCCGCGCGCCTGCTGGAGCCCTGGGCCGGCTGCAACGGCGGGGCGGCGGCGGACAGCGAC
TCGAGCCTGGACGAGCCGTGCCGCCCCGGCTTCGCCTCGGAATCCAAGGTGTAG
|
| Target 1 GenBank Gene ID |
|
| Target 1 GeneCard ID |
ADRB1 |
| Target 1 GenAtlas ID |
ADRB1 |
| Target 1 HGNC ID |
HGNC:285 |
| Target 1 Chromosome Location |
10 |
| Target 1 Locus |
10q24-q26 |
| Target 1 SNPs |
SNPJam Report |
| Target 1 General References |
- Mason DA, Moore JD, Green SA, Liggett SB: A gain-of-function polymorphism in a G-protein coupling domain of the human beta1-adrenergic receptor. J Biol Chem. 1999 Apr 30;274(18):12670-4. [PubMed ]
- Moore JD, Mason DA, Green SA, Hsu J, Liggett SB: Racial differences in the frequencies of cardiac beta(1)-adrenergic receptor polymorphisms: analysis of c145A>G and c1165G>C. Hum Mutat. 1999 Sep 19;14(3):271. [PubMed ]
- Borjesson M, Magnusson Y, Hjalmarson A, Andersson B: A novel polymorphism in the gene coding for the beta(1)-adrenergic receptor associated with survival in patients with heart failure. Eur Heart J. 2000 Nov;21(22):1853-8. [PubMed ]
- Ranade K, Jorgenson E, Sheu WH, Pei D, Hsiung CA, Chiang FT, Chen YD, Pratt R, Olshen RA, Curb D, Cox DR, Botstein D, Risch N: A polymorphism in the beta1 adrenergic receptor is associated with resting heart rate. Am J Hum Genet. 2002 Apr;70(4):935-42. Epub 2002 Feb 18. [PubMed ]
- Frielle T, Collins S, Daniel KW, Caron MG, Lefkowitz RJ, Kobilka BK: Cloning of the cDNA for the human beta 1-adrenergic receptor. Proc Natl Acad Sci U S A. 1987 Nov;84(22):7920-4. [PubMed ]
|
| Target 1 Drug References |
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed ]
- 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 ]
- Kirshenbaum JM: Nonthrombolytic intervention in acute myocardial infarction. Am J Cardiol. 1989 Jul 18;64(4):25B-28B. [PubMed ]
- 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 ]
- 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 ]
- 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 ]
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