Identification

Name
Etomidate
Accession Number
DB00292  (APRD00965)
Type
Small Molecule
Groups
Approved
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
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AmidateInjection, solution2 mg/1mLIntravenousGeneral Injectables & Vaccines2010-03-102017-06-19Us
AmidateInjection, solution2 mg/1mLIntravenousHospira, Inc.2005-10-07Not applicableUs
AmidateInjection, solution2 mg/1mLIntravenousHospira, Inc.2005-07-26Not applicableUs
AmidateInjection, solution2 mg/1mLIntravenousGeneral Injectables & Vaccines, Inc2010-08-01Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
EtomidateInjection, solution2 mg/1mLIntravenousMylan Institutional2012-02-03Not applicableUs
EtomidateInjection, solution2 mg/1mLIntravenousPar Pharmaceutical2014-06-242015-01-15Us
EtomidateInjection, solution2 mg/1mLIntravenousSandoz2009-04-012011-09-27Us
EtomidateInjection, solution20 mg/10mLIntravenousAuro Medics Pharma Llc2017-02-24Not applicableUs
EtomidateInjection, solution2 mg/1mLIntravenousRemedy Repack2018-02-06Not applicableUs
EtomidateInjection, solution2 mg/1mLIntravenousBedford Pharmaceuticals1996-12-012012-02-29Us
EtomidateInjection, solution2 mg/1mLIntravenousPharma Force, Inc.2010-06-082016-06-21Us
EtomidateInjection, solution2 mg/1mLIntravenousSagent Agila2012-06-152012-06-15Us
EtomidateSolution2 mg/1mLIntravenousGland Pharma Limited2017-05-20Not applicableUs
EtomidateInjection2 mg/1mLIntravenousWest-Ward Pharmaceuticals Corp2016-02-25Not applicableUs
International/Other Brands
Hypnomidate (Janssen)
Categories
UNII
Z22628B598
CAS number
33125-97-2
Weight
Average: 244.289
Monoisotopic: 244.121177766
Chemical Formula
C14H16N2O2
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

Pharmacology

Indication

Used in the induction of general anesthesia.

Associated Therapies
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
Human
AAlpha-2B adrenergic receptor
agonist
Human
AGABA-A receptor (anion channel)
positive allosteric modulator
Human
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
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.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic AcidThe risk or severity of hypertension can be increased when Etomidate is combined with 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid.
1-benzylimidazoleThe risk or severity of hypertension can be increased when Etomidate is combined with 1-benzylimidazole.
2,5-Dimethoxy-4-ethylamphetamineThe risk or severity of hypertension can be increased when Etomidate is combined with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when Etomidate is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineThe risk or severity of adverse effects can be increased when Etomidate is combined with 3,4-Methylenedioxyamphetamine.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when Etomidate is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when Etomidate is combined with 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of adverse effects can be increased when Etomidate is combined with 5-methoxy-N,N-dimethyltryptamine.
7-NitroindazoleThe risk or severity of adverse effects can be increased when Etomidate is combined with 7-Nitroindazole.
AbacavirEtomidate may decrease the excretion rate of Abacavir which could result in a higher serum level.
Food Interactions
Not 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 References
Not Available
External Links
Human Metabolome Database
HMDB0014437
KEGG Drug
D00548
KEGG Compound
C07522
PubChem Compound
667484
PubChem Substance
46507012
ChemSpider
580864
BindingDB
50125935
ChEBI
4910
ChEMBL
CHEMBL681
Therapeutic Targets Database
DAP000669
PharmGKB
PA164743987
Drugs.com
Drugs.com Drug Page
Wikipedia
Etomidate
ATC Codes
N01AX07 — Etomidate

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2, 3Active Not RecruitingTreatmentCritical Illness1
3RecruitingTreatmentStrokes1
3WithdrawnNot AvailableHigh Blood Pressure (Hypertension)1
4Active Not RecruitingTreatmentAnaesthesia therapy / Electroconvulsive Therapy1
4CompletedPreventionAdrenocortical Deficiency / Hemodynamics Instability1
4CompletedPreventionInduction of Anaesthesia1
4CompletedTreatmentAirway Control / Anaesthesia therapy / Complications / Intubations1
4CompletedTreatmentCholangiocarcinomas / Choledocholithiasis / Malignant Neoplasm of Pancreas / Pancreatitis1
4CompletedTreatmentConscious Sedation Failure During Procedure1
4CompletedTreatmentCoronary Artery Disease / Mitral Valve Regurgitation1
4CompletedTreatmentCoronary Artery Disease / Valvular Heart Disease1
4CompletedTreatmentIntubation; Difficult1
4CompletedTreatmentSurgery, Cardiac1
4Not Yet RecruitingTreatmentDelirium / Hemodynamics Instability1
4Not Yet RecruitingTreatmentMyoclonus1
4RecruitingTreatmentCardio Respiratory Arrest / Respiratory Arrest1
4RecruitingTreatmentDepression1
4RecruitingTreatmentIntubation Complications1
4Unknown StatusTreatmentAnaesthesia therapy / Hemodynamics / Oxidative Stress1
4Unknown StatusTreatmentAnaesthesia therapy / Pregnancy Termination1
4Unknown StatusTreatmentBispectral Index / Etomidate / Induction / Pediatric1
4Unknown StatusTreatmentCongenital Choledochal Cyst / Congenital Hydronephrosis / Fracture Bone1
4Unknown StatusTreatmentCoronary Artery Bypass Graft Surgery Patients1
4Unknown StatusTreatmentHemodynamics / Hysteroscopy / Sedation therapy1
4Unknown StatusTreatmentAdjunct to general anesthesia therapy / Target Controlled Infusion (TCI)1
Not AvailableCompletedNot AvailableNeuromuscular Monitoring1
Not AvailableCompletedBasic ScienceDepression1
Not AvailableCompletedPreventionAdrenal Insufficiency1
Not AvailableCompletedTreatmentComplication of Gastrostomy1
Not AvailableCompletedTreatmentMajor Depressive Disorder (MDD)1
Not AvailableCompletedTreatmentSepsis / Traumas1
Not AvailableRecruitingTreatmentIschemia, Brain / Strokes1
Not AvailableRecruitingTreatmentPostoperative Complications1
Not AvailableWithdrawnNot AvailableTraumas1

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
InjectionIntravenous2 mg/1mL
Injection, solutionIntravenous2 mg/1mL
Injection, solutionIntravenous20 mg/10mL
Injection, solutionIntravenous40 mg/20mL
SolutionIntravenous2 mg/1mL
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)4.54ChemAxon
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 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-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

Taxonomy

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
Imidazole-4-carbonyl group / Monocyclic benzene moiety / Benzenoid / N-substituted imidazole / Heteroaromatic compound / Carboxylic acid ester / Carboxylic acid derivative / Monocarboxylic acid or derivatives / Azacycle / Organic nitrogen compound
show 7 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
ethyl ester, imidazoles (CHEBI:4910)

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...
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. [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...
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. [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]

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 cytochro...
Gene Name
CYP11B1
Uniprot ID
P15538
Uniprot Name
Cytochrome P450 11B1, mitochondrial
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
Uniprot Name
Cytochrome P450 11B2, mitochondrial
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
Uniprot Name
Aromatase
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 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. [PubMed:10927023]

Drug created on June 13, 2005 07:24 / Updated on December 12, 2018 13:12