U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C14H16N2O2
Molecular Weight 244.289
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ETOMIDATE

SMILES

CCOC(=O)C1=CN=CN1[C@H](C)C2=CC=CC=C2

InChI

InChIKey=NPUKDXXFDDZOKR-LLVKDONJSA-N
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

HIDE SMILES / InChI

Description
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/mesh/68005045 | https://www.ncbi.nlm.nih.gov/pubmed/21263301 | https://academic.oup.com/bjaed/article/6/2/49/305039/The-molecular-mechanisms-of-general-anaesthesia

Etomidate (AMIDATE®) is an imidazole derivative anesthetic and hypnotic with little effect on blood gases, ventilation, or the cardiovascular system. It is intended for the induction of general anesthesia by intravenous injection. Etomidate (AMIDATE®) is also indicated for the supplementation of subpotent anesthetic agents, such as nitrous oxide in oxygen, during maintenance of anesthesia for short operative procedures such as dilation and curettage or cervical conization. It also produces a unique toxicity among anesthetic drugs - inhibition of adrenal steroid synthesis that far outlasts its hypnotic action and that may reduce survival of critically ill patients. The major molecular targets mediating anesthetic effects of etomidate (AMIDATE®) in the central nervous system are specific gamma-aminobutyric acid (GABA) type A receptor subtypes. The R(+) isomer of etomidate is 10 times more potent than its S(-) isomer at potentiating GABA-A receptor activity.

CNS Activity

Curator's Comment: Etomidate is supposed to be neuroprotective.

Originator

Curator's Comment: # Janssen Pharmaceuticals, a division of Ortho-McNeil-Jannsen Pharmaceuticals

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
AMIDATE

Approved Use

Etomidate injection, USP is indicated by intravenous injection for the induction of general anesthesia. When considering use of etomidate, the usefulness of its hemodynamic properties (see CLINICAL PHARMACOLOGY) should be weighed against the high frequency of transient skeletal muscle movements (see ADVERSE REACTIONS). Intravenous etomidate is also indicated for the supplementation of subpotent anesthetic agents, such as nitrous oxide in oxygen, during maintenance of anesthesia for short operative procedures such as dilation and curettage or cervical conization.

Launch Date

1982
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
87 ng/mL
25 mg 1 times / day multiple, oral
dose: 25 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
ETOMIDATE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
3263 ng × min/mL
25 mg 1 times / day multiple, oral
dose: 25 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
ETOMIDATE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
75 min
25 mg 1 times / day multiple, oral
dose: 25 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
ETOMIDATE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer







Drug as perpetrator​Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Total intravenous anesthesia with etomidate. III. Some observations in adults.
1977
Respiratory effects of etomidate.
1977 Mar
Etomidate in a new solvent. A clinical evaluation.
1977 Nov-Dec
Effect of premedication on etomidate anaesthesia.
1979 Dec
Comparison of etomidate in combination with fentanyl or diazepam, with thiopentone as an induction agent for general anaesthesia.
1979 Dec
Venous complications after intravenous injection of diazepam, flunitrazepam, thiopentone and etomidate.
1980 Jun
Etomidate: a foreshortened clinical trial.
1980 Nov
Pain and myoclonus during induction with etomidate. A double-blind, controlled evaluation of the influence of droperidol and fentanyl.
1981
Epileptiform seizures during prolonged etomidate sedation.
1983 Aug 27
Cardiac complications during use of etomidate.
1983 Dec
The safety of etomidate: a new intravenous anaesthetic induction agent.
1983 Jun
[Etomidate in Intralipid. A solution for pain-free injection].
1983 Oct
Venous reactions following etomidate.
1984 Aug
Alfentanil in minor gynaecological surgery: use with etomidate and a comparison with halothane.
1984 Aug
Venous sequelae following the injection of etomidate or thiopentone i.v.
1984 Feb
The prevention of etomidate-induced myoclonus.
1984 Jan
Prolonged myoclonus after etomidate anesthesia.
1985 Jan
[Increased tendency to seizures as affected by long-term infusions of etomidate in delirium tremens].
1985 Sep
Myoclonus on recovery from etomidate.
1985 Sep
Etomidate versus thiopental for induction of anesthesia.
1985 Sep
Hypertension during anaesthesia with monoamine oxidase inhibitors.
1987 Jun
Angioneurotic oedema following etomidate/lignocaine.
1987 Mar
Use of etomidate for elective cardioversion.
1988 Apr
Respiratory disturbance during recovery from etomidate anaesthesia.
1988 Jan
Vecuronium induced bradycardia following induction of anaesthesia with etomidate or thiopentone, with or without fentanyl.
1988 Jan
Etomidate infusions for the control of refractory status epilepticus.
1989
[The modification of injection pain and the incidence of thrombophlebitis following etomidate].
1990 Jan
[Anesthesia for cardioversion. A comparison of propofol and etomidate].
1990 May-Jun
[Etomidate using a new solubilizer. Experimental clinical studies on venous tolerance and bioavailability].
1990 Oct
Excitatory effects and electroencephalographic correlation of etomidate, thiopental, methohexital, and propofol.
1993 Nov
Acute toxicosis in two dogs associated with etomidate-propylene glycol infusion.
1994 Dec
Propylene glycol toxicity following continuous etomidate infusion for the control of refractory cerebral edema.
1995 Aug
Total intravenous anesthesia for children undergoing brief diagnostic or therapeutic procedures.
1995 Jun
Propylene glycol toxicity caused by prolonged infusion of etomidate.
1995 Oct
Focal cerebral ischemia during anesthesia with etomidate, isoflurane, or thiopental: a comparison of the extent of cerebral injury.
1995 Oct
Cerebral hypoxia after etomidate administration and temporary cerebral artery occlusion.
1997 Oct
An unexpected arousal effect of etomidate in a patient on high-dose steroids.
1998 Dec
Anesthesia sensitivity in mice that lack the beta3 subunit of the gamma-aminobutyric acid type A receptor.
1998 Mar
Vascular effects of etomidate administered for electroencephalographic burst suppression in humans.
1998 Oct
Reducing myoclonus after etomidate.
1999 Jan
Fatal outcome during anaesthesia induction in a patient with amiodarone-induced thyrotoxicosis.
2008 Apr
Pretreatment of rocuronium reduces the frequency and severity of etomidate-induced myoclonus.
2008 Dec
Cytotoxicity and decreased corticosterone production in adrenocortical Y-1 cells by 3-methylsulfonyl-DDE and structurally related molecules.
2009 Apr
Cardiovascular manifestations of sedatives and analgesics in the critical care unit.
2009 Jul-Aug
Epileptic seizure during anaesthesia induction with etomidate.
2010 Jun
Pretreatment with dexmedetomidine or thiopental decreases myoclonus after etomidate: a randomized, double-blind controlled trial.
2010 Mar
Does lidocaine more effectively prevent pain upon induction with propofol or etomidate when given preemptively than when mixed with the drug?
2010 Nov
GABAA receptor open-state conformation determines non-competitive antagonist binding.
2011 Feb 1
Etomidate deteriorates the toxicity of advanced glycation end products to human endothelial Eahy926 cells.
2014
Prevention of etomidate-induced myoclonus: which is superior: Fentanyl, midazolam, or a combination? A Retrospective comparative study.
2014 Feb 16
Patents

Sample Use Guides

Etomidate (AMIDATE®) is intended for administration only by the intravenous route. The dose for induction of anesthesia in adult patients will vary between 0.2 and 0.6 mg/kg of body weight, and it must be individualized in each case. The usual dose for induction in these patients is 0.3 mg/kg, injected over a period of 30 to 60 seconds.
Route of Administration: Intravenous
In Vitro Use Guide
The effect of etomidate on GABA-A receptor function was studied in cultured rat hippocampal neurons. At a clinically relevant concentration of 4.1 microM, etomidate shifts the GABA dose response to the left (ED50 shift from 10.2 to 5.2 microM), with no change in the maximum current evoked by saturating concentrations of GABA. At a higher concentration of 82 microM, etomidate directly induces current in the absence of GABA. Analysis of single channels opened by GABA indicates that 8.2 microM etomidate increases the probability of channels being open 13-fold and increases the effective channel open time two-fold.
Name Type Language
ETOMIDATE
EP   INN   MART.   MI   ORANGE BOOK   USAN   USP-RS   VANDF   WHO-DD  
USAN   INN  
Official Name English
AMIDATE
Brand Name English
(+)-ETHYL 1-(.ALPHA.-METHYLBENZYL)IMIDAZOLE-5-CARBOXYLATE
Systematic Name English
etomidate [INN]
Common Name English
IMIDAZOLE-5-CARBOXYLIC ACID, 1-(.ALPHA.-METHYLBENZYL)-, ETHYL ESTER, (R)-(+)-
Systematic Name English
ETOMIDATE [ORANGE BOOK]
Common Name English
ETOMIDATE [EP MONOGRAPH]
Common Name English
ETOMIDATE [USAN]
Common Name English
ETOMIDATE [VANDF]
Common Name English
Etomidate [WHO-DD]
Common Name English
NSC-759160
Code English
HYPNOMIDATE
Brand Name English
ETOMIDATE [USP MONOGRAPH]
Common Name English
1H-IMIDAZOLE-5-CARBOXYLIC ACID, 1-(1-PHENYLETHYL)-, ETHYL ESTER, (+)-
Common Name English
ETOMIDATE [MART.]
Common Name English
ETOMIDATE [USP-RS]
Common Name English
ETOMIDATE [MI]
Common Name English
Classification Tree Code System Code
WHO-ATC N01AX07
Created by admin on Fri Dec 15 15:34:08 GMT 2023 , Edited by admin on Fri Dec 15 15:34:08 GMT 2023
WHO-VATC QN01AX07
Created by admin on Fri Dec 15 15:34:08 GMT 2023 , Edited by admin on Fri Dec 15 15:34:08 GMT 2023
NDF-RT N0000175681
Created by admin on Fri Dec 15 15:34:08 GMT 2023 , Edited by admin on Fri Dec 15 15:34:08 GMT 2023
NCI_THESAURUS C245
Created by admin on Fri Dec 15 15:34:08 GMT 2023 , Edited by admin on Fri Dec 15 15:34:08 GMT 2023
NDF-RT N0000175975
Created by admin on Fri Dec 15 15:34:08 GMT 2023 , Edited by admin on Fri Dec 15 15:34:08 GMT 2023
Code System Code Type Description
DRUG CENTRAL
1109
Created by admin on Fri Dec 15 15:34:08 GMT 2023 , Edited by admin on Fri Dec 15 15:34:08 GMT 2023
PRIMARY
EPA CompTox
DTXSID5023033
Created by admin on Fri Dec 15 15:34:08 GMT 2023 , Edited by admin on Fri Dec 15 15:34:08 GMT 2023
PRIMARY
RXCUI
4177
Created by admin on Fri Dec 15 15:34:08 GMT 2023 , Edited by admin on Fri Dec 15 15:34:08 GMT 2023
PRIMARY RxNorm
CAS
33125-97-2
Created by admin on Fri Dec 15 15:34:08 GMT 2023 , Edited by admin on Fri Dec 15 15:34:08 GMT 2023
PRIMARY
IUPHAR
5463
Created by admin on Fri Dec 15 15:34:08 GMT 2023 , Edited by admin on Fri Dec 15 15:34:08 GMT 2023
PRIMARY
FDA UNII
Z22628B598
Created by admin on Fri Dec 15 15:34:08 GMT 2023 , Edited by admin on Fri Dec 15 15:34:08 GMT 2023
PRIMARY
MERCK INDEX
m5196
Created by admin on Fri Dec 15 15:34:08 GMT 2023 , Edited by admin on Fri Dec 15 15:34:08 GMT 2023
PRIMARY Merck Index
NCI_THESAURUS
C47527
Created by admin on Fri Dec 15 15:34:08 GMT 2023 , Edited by admin on Fri Dec 15 15:34:08 GMT 2023
PRIMARY
RS_ITEM_NUM
1268750
Created by admin on Fri Dec 15 15:34:08 GMT 2023 , Edited by admin on Fri Dec 15 15:34:08 GMT 2023
PRIMARY
ECHA (EC/EINECS)
251-385-9
Created by admin on Fri Dec 15 15:34:08 GMT 2023 , Edited by admin on Fri Dec 15 15:34:08 GMT 2023
PRIMARY
DAILYMED
Z22628B598
Created by admin on Fri Dec 15 15:34:08 GMT 2023 , Edited by admin on Fri Dec 15 15:34:08 GMT 2023
PRIMARY
PUBCHEM
667484
Created by admin on Fri Dec 15 15:34:08 GMT 2023 , Edited by admin on Fri Dec 15 15:34:08 GMT 2023
PRIMARY
MESH
D005045
Created by admin on Fri Dec 15 15:34:08 GMT 2023 , Edited by admin on Fri Dec 15 15:34:08 GMT 2023
PRIMARY
ChEMBL
CHEMBL681
Created by admin on Fri Dec 15 15:34:08 GMT 2023 , Edited by admin on Fri Dec 15 15:34:08 GMT 2023
PRIMARY
EVMPD
SUB07330MIG
Created by admin on Fri Dec 15 15:34:08 GMT 2023 , Edited by admin on Fri Dec 15 15:34:08 GMT 2023
PRIMARY
WIKIPEDIA
ETOMIDATE
Created by admin on Fri Dec 15 15:34:08 GMT 2023 , Edited by admin on Fri Dec 15 15:34:08 GMT 2023
PRIMARY
NSC
759160
Created by admin on Fri Dec 15 15:34:08 GMT 2023 , Edited by admin on Fri Dec 15 15:34:08 GMT 2023
PRIMARY
SMS_ID
100000082107
Created by admin on Fri Dec 15 15:34:08 GMT 2023 , Edited by admin on Fri Dec 15 15:34:08 GMT 2023
PRIMARY
CHEBI
4910
Created by admin on Fri Dec 15 15:34:08 GMT 2023 , Edited by admin on Fri Dec 15 15:34:08 GMT 2023
PRIMARY
INN
1926
Created by admin on Fri Dec 15 15:34:08 GMT 2023 , Edited by admin on Fri Dec 15 15:34:08 GMT 2023
PRIMARY
DRUG BANK
DB00292
Created by admin on Fri Dec 15 15:34:08 GMT 2023 , Edited by admin on Fri Dec 15 15:34:08 GMT 2023
PRIMARY
LACTMED
Etomidate
Created by admin on Fri Dec 15 15:34:08 GMT 2023 , Edited by admin on Fri Dec 15 15:34:08 GMT 2023
PRIMARY