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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
SynonymLanguageCode
(+)-ethyl 1-(α-methylbenzyl)imidazole-5-carboxylateNot AvailableNot Available
(+)-etomidateNot AvailableNot Available
(R)-1-(1-phenylethyl)-1H-imidazole-5-carboxylic acid ethyl esterNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
AmidateNot Available
HypnomidateNot Available
Brand mixturesNot Available
Categories
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[C@H](C)C1=CC=CC=C1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassPhenethylamines
Direct parentPhenethylamines
Alternative parentsCarbonylimidazoles; N-substituted Imidazoles; Carboxylic Acid Esters; Enolates; Dialkyl Ethers; Polyamines
Substituentsimidazole-4-carbonyl group; n-substituted imidazole; azole; imidazole; carboxylic acid ester; polyamine; carboxylic acid derivative; enolate; dialkyl ether; ether; amine; organonitrogen compound
Classification descriptionThis compound belongs to the phenethylamines. These are compounds containing a phenethylamine moiety, which consists of a phenyl group substituted at the second position by an ethan-1-amine.
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.
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
Property Value Probability
Human Intestinal Absorption + 0.9908
Blood Brain Barrier + 0.95
Caco-2 permeable + 0.6275
P-glycoprotein substrate Non-substrate 0.7386
P-glycoprotein inhibitor I Non-inhibitor 0.8567
P-glycoprotein inhibitor II Non-inhibitor 0.8597
Renal organic cation transporter Non-inhibitor 0.7918
CYP450 2C9 substrate Non-substrate 0.7947
CYP450 2D6 substrate Non-substrate 0.9117
CYP450 3A4 substrate Non-substrate 0.7671
CYP450 1A2 substrate Inhibitor 0.9107
CYP450 2C9 substrate Non-inhibitor 0.9071
CYP450 2D6 substrate Non-inhibitor 0.9231
CYP450 2C19 substrate Inhibitor 0.5432
CYP450 3A4 substrate Inhibitor 0.7959
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.8357
Ames test Non AMES toxic 0.7989
Carcinogenicity Non-carcinogens 0.8795
Biodegradation Not ready biodegradable 0.5121
Rat acute toxicity 2.5459 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9622
hERG inhibition (predictor II) Non-inhibitor 0.8553
Pharmacoeconomics
Manufacturers
  • Hospira inc
  • Bedford laboratories div ben venue laboratories inc
  • Parenta pharmaceuticals inc
  • Pharmaforce inc
Packagers
Dosage forms
FormRouteStrength
SolutionIntravenous
Prices
Unit descriptionCostUnit
Amidate 2 mg/ml vial1.55USDml
Amidate 2 mg/ml ampul1.19USDml
Etomidate 2 mg/ml vial1.18USDml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point67 °CPhysProp
water solubility63.2 mg/LNot Available
logP3.05POMONA (1987)
Predicted Properties
PropertyValueSource
water solubility4.77e-01 g/lALOGPS
logP2.66ALOGPS
logP2.5ChemAxon
logS-2.7ALOGPS
pKa (strongest basic)4.54ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count2ChemAxon
hydrogen donor count0ChemAxon
polar surface area44.12ChemAxon
rotatable bond count5ChemAxon
refractivity69.59ChemAxon
polarizability26.43ChemAxon
number of rings2ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
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 ReferenceNot Available
External Links
ResourceLink
KEGG DrugD00548
KEGG CompoundC07522
BindingDB50125938
ChEBI4910
ChEMBLCHEMBL681
Therapeutic Targets DatabaseDAP000669
PharmGKBPA164743987
Drugs.comhttp://www.drugs.com/cdi/etomidate.html
WikipediaEtomidate
ATC CodesN01AX07
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

1. Gamma-aminobutyric acid receptor subunit alpha-1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Gamma-aminobutyric acid receptor subunit alpha-1 P14867 Details

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
  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
  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. Pubmed
  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. Pubmed
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Alpha-2B adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Alpha-2B adrenergic receptor P18089 Details

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
  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

3. GABA-A receptor (anion channel)

Kind: protein group

Organism: Human

Pharmacological action: yes

Actions: positive allosteric modulator

Components

Name UniProt ID Details
Gamma-aminobutyric acid receptor subunit alpha-1 P14867 Details
Gamma-aminobutyric acid receptor subunit alpha-2 P47869 Details
Gamma-aminobutyric acid receptor subunit alpha-3 P34903 Details
Gamma-aminobutyric acid receptor subunit alpha-4 P48169 Details
Gamma-aminobutyric acid receptor subunit alpha-5 P31644 Details
Gamma-aminobutyric acid receptor subunit alpha-6 Q16445 Details
Gamma-aminobutyric acid receptor subunit beta-1 P18505 Details
Gamma-aminobutyric acid receptor subunit beta-2 P47870 Details
Gamma-aminobutyric acid receptor subunit beta-3 P28472 Details
Gamma-aminobutyric acid receptor subunit delta O14764 Details
Gamma-aminobutyric acid receptor subunit epsilon P78334 Details
Gamma-aminobutyric acid receptor subunit gamma-1 Q8N1C3 Details
Gamma-aminobutyric acid receptor subunit gamma-2 P18507 Details
Gamma-aminobutyric acid receptor subunit gamma-3 Q99928 Details
Gamma-aminobutyric acid receptor subunit pi O00591 Details
Gamma-aminobutyric acid receptor subunit theta Q9UN88 Details

References:

  1. ChEMBL Compound Report Card (Accessed December 2013)

1. Cytochrome P450 11B1, mitochondrial

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 11B1, mitochondrial P15538 Details

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

2. Cytochrome P450 11B2, mitochondrial

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 11B2, mitochondrial P19099 Details

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

3. Cytochrome P450 19A1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 19A1 P11511 Details

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

1. Solute carrier family 2, facilitated glucose transporter member 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 2, facilitated glucose transporter member 1 P11166 Details

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

Comments
Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:09