Etomidate

Identification

Summary

Etomidate is a short-acting intravenous anesthetic indicated for the induction of anesthesia and supplementation of subpotent anesthesia during short operative procedures.

Brand Names
Amidate
Generic Name
Etomidate
DrugBank Accession Number
DB00292
Background

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

Type
Small Molecule
Groups
Approved
Structure
Weight
Average: 244.289
Monoisotopic: 244.121177766
Chemical Formula
C14H16N2O2
Synonyms
  • (+)-ethyl 1-(α-methylbenzyl)imidazole-5-carboxylate
  • (+)-etomidate
  • (R)-(+)-1-(α-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

Pharmacology

Indication

Used in the induction of general anesthesia.

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Associated Therapies
Contraindications & Blackbox Warnings
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Pharmacodynamics

Etomidate 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 action

Etomidate 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.

TargetActionsOrganism
AGamma-aminobutyric acid receptor subunit alpha-1
agonist
Humans
AAlpha-2B adrenergic receptor
agonist
Humans
AGABA(A) Receptor
positive allosteric modulator
Humans
Absorption

Not Available

Volume of distribution

Not Available

Protein binding

76%, primarily to serum albumin.

Metabolism

Hepatic. Metabolized rapidly by ester hydrolysis to inactive metabolites.

Route of elimination

Approximately 75% of the administered dose is excreted in the urine during the first day after injection.

Half-life

75 minutes.

Clearance

Not Available

Adverse Effects
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Toxicity

Undesirable 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.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
1,2-BenzodiazepineThe risk or severity of CNS depression can be increased when Etomidate is combined with 1,2-Benzodiazepine.
AbacavirEtomidate may decrease the excretion rate of Abacavir which could result in a higher serum level.
AcebutololThe therapeutic efficacy of Etomidate can be decreased when used in combination with Acebutolol.
AceclofenacThe risk or severity of hypertension can be increased when Etomidate is combined with Aceclofenac.
AcemetacinThe risk or severity of hypertension can be increased when Etomidate is combined with Acemetacin.
Food Interactions
No interactions found.

Products

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International/Other Brands
Hypnomidate (Janssen)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
AmidateInjection, solution2 mg/1mLIntravenousHospira, Inc.2006-11-072006-11-07US flag
AmidateInjection, solution2 mg/1mLIntravenousHenry Schein, Inc.2022-01-06Not applicableUS flag
AmidateInjection, solution2 mg/1mLIntravenousGeneral Injectables & Vaccines, Inc2010-08-012023-05-01US flag
AmidateInjection, solution2 mg/1mLIntravenousHospira, Inc.2005-07-26Not applicableUS flag
AmidateInjection, solution2 mg/1mLIntravenousHospira, Inc.2006-11-072006-11-07US flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
EtomidateInjection, solution2 mg/1mLIntravenousFresenius Kabi USA, LLC2023-10-01Not applicableUS flag
EtomidateInjection, solution2 mg/1mLIntravenousBedford Pharmaceuticals1996-12-012012-02-29US flag
EtomidateInjection, solution2 mg/1mLIntravenousREMEDYREPACK INC.2018-02-062020-05-07US flag
EtomidateInjection, solution2 mg/1mLIntravenousMylan Institutional LLC2019-03-01Not applicableUS flag
EtomidateInjection, solution2 mg/1mLIntravenousMylan Institutional LLC2012-02-032018-03-31US flag

Categories

ATC Codes
N01AX07 — Etomidate
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as carbonylimidazoles. These are substituted imidazoles in which the imidazole ring bears a carbonyl group.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Azoles
Sub Class
Imidazoles
Direct Parent
Carbonylimidazoles
Alternative Parents
N-substituted imidazoles / Benzene and substituted derivatives / Heteroaromatic compounds / Carboxylic acid esters / Monocarboxylic acids and derivatives / Azacyclic compounds / Organopnictogen compounds / Organooxygen compounds / Organonitrogen compounds / Organic oxides
show 1 more
Substituents
Aromatic heteromonocyclic compound / Azacycle / Benzenoid / Carboxylic acid derivative / Carboxylic acid ester / Heteroaromatic compound / Hydrocarbon derivative / Imidazole-4-carbonyl group / Monocarboxylic acid or derivatives / Monocyclic benzene moiety
show 7 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
ethyl ester, imidazoles (CHEBI:4910)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
Z22628B598
CAS number
33125-97-2
InChI Key
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

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 References
Not Available
Human Metabolome Database
HMDB0014437
KEGG Drug
D00548
KEGG Compound
C07522
PubChem Compound
667484
PubChem Substance
46507012
ChemSpider
580864
BindingDB
50125935
RxNav
4177
ChEBI
4910
ChEMBL
CHEMBL681
ZINC
ZINC000000001408
Therapeutic Targets Database
DAP000669
PharmGKB
PA164743987
PDBe Ligand
V8D
Drugs.com
Drugs.com Drug Page
Wikipedia
Etomidate
PDB Entries
6x3v / 8f6y / 8pvb

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedPreventionAdrenocortical Deficiency / Hemodynamics Instability1
4CompletedPreventionInduction of Anaesthesia1
4CompletedScreeningHemodynamics / Side Effects1
4CompletedSupportive CareSurgery1
4CompletedTreatmentAirway Control / Anesthesia therapy / Complications / Intubation1

Pharmacoeconomics

Manufacturers
  • Hospira inc
  • Bedford laboratories div ben venue laboratories inc
  • Parenta pharmaceuticals inc
  • Pharmaforce inc
Packagers
  • American Regent
  • Bedford Labs
  • Ben Venue Laboratories Inc.
  • Ebewe Pharma
  • General Injectables and Vaccines Inc.
  • Hospira Inc.
Dosage Forms
FormRouteStrength
SolutionIntravenous20.000 mg
SolutionIntravenous20 mg
Injection, emulsionIntravenous2 mg/ml
InjectionIntravenous2 mg/1mL
Injection, solutionIntravenous2 mg/1mL
Injection, solutionIntravenous20 mg/10mL
Injection, solutionIntravenous40 mg/20mL
SolutionIntravenous2 mg/1mL
Emulsion2 mg/1ml
Injection, emulsionIntravenous
InjectionIntravenous20 mg/10ml
EmulsionIntravenous20 mg
EmulsionParenteral2 mg
InjectionIntravenous
Injection, solutionIntravenous2 mg/ml
InjectionIntravenous20 mg
SolutionIntravenous2 mg / mL
EmulsionIntravenous2 mg
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.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)142-142.8Godefroi, 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)4.25Chemaxon
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 RuleNoChemaxon
MDDR-like RuleNoChemaxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-0a6r-2910000000-df43a9b83f023b0bb392
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0005-5910000000-e3e55142d021e58cf423
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0297-2970000000-ab1c97a95da9dcaa9899
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-052b-7900000000-49c3144b2769b573db82
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0007-6920000000-a474ce5287ce573c4d69
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4j-3910000000-ca3a936261938f9917a4
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-006w-7900000000-54ef843e8eb9687f7902
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-167.8104813
predicted
DarkChem Lite v0.1.0
[M-H]-157.00337
predicted
DeepCCS 1.0 (2019)
[M+H]+168.4249813
predicted
DarkChem Lite v0.1.0
[M+H]+159.36137
predicted
DeepCCS 1.0 (2019)
[M+Na]+168.2031813
predicted
DarkChem Lite v0.1.0
[M+Na]+165.45451
predicted
DeepCCS 1.0 (2019)

Targets

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insights and accelerate drug research.
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Kind
Protein
Organism
Humans
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...
Gene Name
GABRA1
Uniprot ID
P14867
Uniprot Name
Gamma-aminobutyric acid receptor subunit alpha-1
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Kind
Protein
Organism
Humans
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...
Gene Name
ADRA2B
Uniprot ID
P18089
Uniprot Name
Alpha-2B adrenergic receptor
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. [Article]
  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. [Article]

Enzymes

Kind
Protein
Organism
Humans
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 cytochro...
Gene Name
CYP11B1
Uniprot ID
P15538
Uniprot Name
Cytochrome P450 11B1, mitochondrial
Molecular Weight
57572.44 Da
References
  1. Weber MM, Lang J, Abedinpour F, Zeilberger K, Adelmann B, Engelhardt D: Different inhibitory effect of etomidate and ketoconazole on the human adrenal steroid biosynthesis. Clin Investig. 1993 Nov;71(11):933-8. [Article]
  2. Hermansson V, Asp V, Bergman A, Bergstrom U, Brandt I: Comparative CYP-dependent binding of the adrenocortical toxicants 3-methylsulfonyl-DDE and o,p'-DDD in Y-1 adrenal cells. Arch Toxicol. 2007 Nov;81(11):793-801. Epub 2007 May 9. [Article]
  3. Hahner S, Sturmer A, Fassnacht M, Hartmann RW, Schewe K, Cochran S, Zink M, Schirbel A, Allolio B: Etomidate unmasks intraadrenal regulation of steroidogenesis and proliferation in adrenal cortical cell lines. Horm Metab Res. 2010 Jun;42(7):528-34. doi: 10.1055/s-0030-1249629. Epub 2010 Mar 29. [Article]
Kind
Protein
Organism
Humans
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
Uniprot Name
Cytochrome P450 11B2, mitochondrial
Molecular Weight
57559.62 Da
References
  1. Hahner S, Sturmer A, Fassnacht M, Hartmann RW, Schewe K, Cochran S, Zink M, Schirbel A, Allolio B: Etomidate unmasks intraadrenal regulation of steroidogenesis and proliferation in adrenal cortical cell lines. Horm Metab Res. 2010 Jun;42(7):528-34. doi: 10.1055/s-0030-1249629. Epub 2010 Mar 29. [Article]

Carriers

Kind
Protein
Organism
Humans
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 b...
Gene Name
SLC2A1
Uniprot ID
P11166
Uniprot Name
Solute carrier family 2, facilitated glucose transporter member 1
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. [Article]

Drug created at June 13, 2005 13:24 / Updated at March 03, 2024 02:23