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Identification
NameEtomidate
Accession NumberDB00292  (APRD00965)
TypeSmall Molecule
GroupsApproved
Description

Imidazole derivative anesthetic and hypnotic with little effect on blood gases, ventilation, or the cardiovascular system. It has been proposed as an induction anesthetic. [PubChem]

Structure
Thumb
Synonyms
(+)-Ethyl 1-(alpha-methylbenzyl)imidazole-5-carboxylate
(+)-ethyl 1-(α-methylbenzyl)imidazole-5-carboxylate
(+)-etomidate
(R)-(+)-1-(alpha-Methylbenzyl)imidazole-5-carboxylic acid ethyl ester
(R)-1-(1-phenylethyl)-1H-imidazole-5-carboxylic acid ethyl ester
3-((R)-1-Phenyl-ethyl)-3H-imidazole-4-carboxylic acid ethyl ester
Etomidate
Etomidato
Etomidatum
R-(+)-Ethyl 1-(1-phenylethyl)-1H-imidazole-5-carboxylate
External Identifiers Not Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Amidateinjection, solution2 mg/mLintravenousHospira, Inc.1982-09-072016-04-23Us
Amidateinjection, solution2 mg/mLintravenousGeneral Injectables & Vaccines, Inc2010-08-012016-04-05Us
Amidateinjection, solution2 mg/mLintravenousGENERAL INJECTABLES AND VACCINES, INC.2010-03-102016-04-05Us
Amidateinjection, solution2 mg/mLintravenousHospira, Inc.1982-09-072016-04-23Us
Amidateinjection, solution2 mg/mLintravenousHospira, Inc.1982-09-072016-04-23Us
Amidateinjection, solution2 mg/mLintravenousHospira, Inc.1982-09-072016-04-23Us
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Etomidateinjection, solution2 mg/mLintravenousMylan Institutional LLC2013-04-262016-04-05Us
Etomidateinjection2 mg/mLintravenousPfizer Laboratories Div Pfizer Inc.2012-02-032016-04-23Us
Etomidateinjection, solution2 mg/mLintravenousCadila Healthcare Limited2015-04-032016-04-05Us
Etomidateinjection, solution2 mg/mLintravenousPharma Force, Inc.2010-06-082016-04-05Us
Etomidateinjection2 mg/mLintravenousWest Ward Pharmaceuticals Corp2016-02-252016-04-23Us
Etomidateinjection, solution2 mg/mLintravenousSagent Pharmaceuticals2012-08-102016-04-05Us
Etomidateinjection2 mg/mLintravenousWest Ward Pharmaceuticals Corp2016-02-252016-04-23Us
Etomidateinjection2 mg/mLintravenousHeritage Pharmaceuticals Inc.2012-09-132016-04-05Us
Etomidateinjection, solution2 mg/mLintravenousZydus Pharmaceuticals (USA) Inc.2015-04-032016-04-05Us
Etomidateinjection2 mg/mLintravenousHeritage Pharmaceuticals Inc.2012-09-132016-04-05Us
Etomidateinjection, solution2 mg/mLintravenousMylan Institutional LLC2012-02-032016-04-05Us
Etomidateinjection, solution2 mg/mLintravenousAmerican Regent, Inc.2010-06-302016-04-23Us
Etomidateinjection, solution2 mg/mLintravenousMylan Institutional LLC2012-02-032016-04-05Us
Etomidateinjection, solution2 mg/mLintravenousAmerican Regent, Inc.2010-06-302016-04-23Us
Over the Counter ProductsNot Available
International Brands
NameCompany
HypnomidateJanssen
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIZ22628B598
CAS number33125-97-2
WeightAverage: 244.289
Monoisotopic: 244.121177766
Chemical FormulaC14H16N2O2
InChI KeyInChIKey=NPUKDXXFDDZOKR-LLVKDONJSA-N
InChI
InChI=1S/C14H16N2O2/c1-3-18-14(17)13-9-15-10-16(13)11(2)12-7-5-4-6-8-12/h4-11H,3H2,1-2H3/t11-/m1/s1
IUPAC Name
ethyl 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylate
SMILES
CCOC(=O)C1=CN=CN1[[email protected]](C)C1=CC=CC=C1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as n-substituted imidazoles. These are heterocyclic compounds containing an imidazole ring substituted at position 1.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassAzoles
Sub ClassImidazoles
Direct ParentN-substituted imidazoles
Alternative Parents
Substituents
  • Benzenoid
  • N-substituted imidazole
  • Monocyclic benzene moiety
  • Heteroaromatic compound
  • Carboxylic acid ester
  • Azacycle
  • Monocarboxylic acid or derivatives
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Pharmacology
IndicationUsed in the induction of general anesthesia.
PharmacodynamicsEtomidate is a non-barbiturate hypnotic that acts at the level of the reticular-activating system to produce anesthesia. Etomidate is an imidazole compound that appears to depress CNS function via GABA. Duration of action is intermediate between thiopental and methohexital, and recovery from a single dose is rapid with little residual depression. Like the barbiturates and propofol, etomidate is does not induce analgesia. Etomidate induces unconsciousness within one circulation time. Recovery is rapid as a result of extensive redistribution and rapid metabolism.
Mechanism of actionEtomidate binds at a distinct binding site associated with a Cl- ionopore at the GABAA receptor, increasing the duration of time for which the Cl- ionopore is open. The post-synaptic inhibitory effect of GABA in the thalamus is, therefore, prolonged.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein binding76%, primarily to serum albumin.
Metabolism

Hepatic. Metabolized rapidly by ester hydrolysis to inactive metabolites.

Route of eliminationApproximately 75% of the administered dose is excreted in the urine during the first day after injection.
Half life75 minutes.
ClearanceNot Available
ToxicityUndesirable side effects of etomidate that may limit its use include pain on injection, myoclonus and adrenocortical suppression lasting 4-6 hours following an induction dose.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9908
Blood Brain Barrier+0.95
Caco-2 permeable+0.6275
P-glycoprotein substrateNon-substrate0.7386
P-glycoprotein inhibitor INon-inhibitor0.8567
P-glycoprotein inhibitor IINon-inhibitor0.8597
Renal organic cation transporterNon-inhibitor0.7918
CYP450 2C9 substrateNon-substrate0.7947
CYP450 2D6 substrateNon-substrate0.9117
CYP450 3A4 substrateNon-substrate0.7671
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorInhibitor0.5432
CYP450 3A4 inhibitorInhibitor0.7959
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8357
Ames testNon AMES toxic0.7989
CarcinogenicityNon-carcinogens0.8795
BiodegradationNot ready biodegradable0.5121
Rat acute toxicity2.5459 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9622
hERG inhibition (predictor II)Non-inhibitor0.8553
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Hospira inc
  • Bedford laboratories div ben venue laboratories inc
  • Parenta pharmaceuticals inc
  • Pharmaforce inc
Packagers
Dosage forms
FormRouteStrength
Injection, solutionintravenous2 mg/mL
Injectionintravenous2 mg/mL
Prices
Unit descriptionCostUnit
Amidate 2 mg/ml vial1.55USD ml
Amidate 2 mg/ml ampul1.19USD ml
Etomidate 2 mg/ml vial1.18USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point142-142.8Godefroi, E.F. and Van Der Eijcken, C.A.M.; U.S. Patent 3,354,173; November 21, 1967; assigned to Janssen Pharrnaceutica NV (Belgium).
water solubility63.2 mg/LNot Available
logP3.05POMONA (1987)
Predicted Properties
PropertyValueSource
Water Solubility0.477 mg/mLALOGPS
logP2.66ALOGPS
logP2.5ChemAxon
logS-2.7ALOGPS
pKa (Strongest Basic)4.54ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area44.12 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity69.59 m3·mol-1ChemAxon
Polarizability26.43 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

Douglas E. Raines, “ETOMIDATE ANALOGUES THAT DO NOT INHIBIT ADRENOCORTICAL STEROID SYNTHESIS.” U.S. Patent US20130079381, issued March 28, 2013.

US20130079381
General ReferencesNot Available
External Links
ATC CodesN01AX07
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
General Function:
Inhibitory extracellular ligand-gated ion channel activity
Specific Function:
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel (By si...
Gene Name:
GABRA1
Uniprot ID:
P14867
Molecular Weight:
51801.395 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
  3. Martin LJ, Oh GH, Orser BA: Etomidate targets alpha5 gamma-aminobutyric acid subtype A receptors to regulate synaptic plasticity and memory blockade. Anesthesiology. 2009 Nov;111(5):1025-35. doi: 10.1097/ALN.0b013e3181bbc961. [PubMed:19809285 ]
  4. Desai R, Ruesch D, Forman SA: Gamma-amino butyric acid type A receptor mutations at beta2N265 alter etomidate efficacy while preserving basal and agonist-dependent activity. Anesthesiology. 2009 Oct;111(4):774-84. doi: 10.1097/ALN.0b013e3181b55fae. [PubMed:19741491 ]
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
General Function:
Epinephrine binding
Specific Function:
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is clonidine > norepinephrine > epinephrine = oxymetazoline > dopamine > p-tyramine = phenylephrine > serotonin > p-synephrine / p-octopamine. For antagonists, the rank order is yohimbine > chlorpromazine > phent...
Gene Name:
ADRA2B
Uniprot ID:
P18089
Molecular Weight:
49565.8 Da
References
  1. Creagh O, Torres H, Rodriguez N, Gatica SR: Alpha-2B adrenergic receptor mediated hemodynamic profile of etomidate. P R Health Sci J. 2010 Jun;29(2):91-5. [PubMed:20496522 ]
  2. Paris A, Philipp M, Tonner PH, Steinfath M, Lohse M, Scholz J, Hein L: Activation of alpha 2B-adrenoceptors mediates the cardiovascular effects of etomidate. Anesthesiology. 2003 Oct;99(4):889-95. [PubMed:14508322 ]
Kind
Protein group
Organism
Human
Pharmacological action
yes
Actions
positive allosteric modulator
General Function:
Inhibitory extracellular ligand-gated ion channel activity
Specific Function:
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel (By similarity).
Components:
NameUniProt IDDetails
Gamma-aminobutyric acid receptor subunit alpha-1P14867 Details
Gamma-aminobutyric acid receptor subunit alpha-2P47869 Details
Gamma-aminobutyric acid receptor subunit alpha-3P34903 Details
Gamma-aminobutyric acid receptor subunit alpha-4P48169 Details
Gamma-aminobutyric acid receptor subunit alpha-5P31644 Details
Gamma-aminobutyric acid receptor subunit alpha-6Q16445 Details
Gamma-aminobutyric acid receptor subunit beta-1P18505 Details
Gamma-aminobutyric acid receptor subunit beta-2P47870 Details
Gamma-aminobutyric acid receptor subunit beta-3P28472 Details
Gamma-aminobutyric acid receptor subunit deltaO14764 Details
Gamma-aminobutyric acid receptor subunit epsilonP78334 Details
Gamma-aminobutyric acid receptor subunit gamma-1Q8N1C3 Details
Gamma-aminobutyric acid receptor subunit gamma-2P18507 Details
Gamma-aminobutyric acid receptor subunit gamma-3Q99928 Details
Gamma-aminobutyric acid receptor subunit piO00591 Details
Gamma-aminobutyric acid receptor subunit thetaQ9UN88 Details
References
  1. ChEMBL Compound Report Card [Link]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Steroid 11-beta-monooxygenase activity
Specific Function:
Has steroid 11-beta-hydroxylase activity. In addition to this activity, the 18 or 19-hydroxylation of steroids and the aromatization of androstendione to estrone have also been ascribed to cytochrome P450 XIB.
Gene Name:
CYP11B1
Uniprot ID:
P15538
Molecular Weight:
57572.44 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Steroid 11-beta-monooxygenase activity
Specific Function:
Preferentially catalyzes the conversion of 11-deoxycorticosterone to aldosterone via corticosterone and 18-hydroxycorticosterone.
Gene Name:
CYP11B2
Uniprot ID:
P19099
Molecular Weight:
57559.62 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Oxygen binding
Specific Function:
Catalyzes the formation of aromatic C18 estrogens from C19 androgens.
Gene Name:
CYP19A1
Uniprot ID:
P11511
Molecular Weight:
57882.48 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Xenobiotic transporter activity
Specific Function:
Facilitative glucose transporter. This isoform may be responsible for constitutive or basal glucose uptake. Has a very broad substrate specificity; can transport a wide range of aldoses including both pentoses and hexoses.
Gene Name:
SLC2A1
Uniprot ID:
P11166
Molecular Weight:
54083.325 Da
References
  1. Stephenson KN, Croxen RL, El-Barbary A, Fenstermacher JD, Haspel HC: Inhibition of glucose transport and direct interactions with type 1 facilitative glucose transporter (GLUT-1) by etomidate, ketamine, and propofol: a comparison with barbiturates. Biochem Pharmacol. 2000 Sep 1;60(5):651-9. [PubMed:10927023 ]
Comments
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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:09