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Details

Stereochemistry ABSOLUTE
Molecular Formula C14H16N2O2.ClH
Molecular Weight 280.75
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ETOMIDATE HYDROCHLORIDE

SMILES

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

InChI

InChIKey=NCDXBSVHIGDPOE-RFVHGSKJSA-N
InChI=1S/C14H16N2O2.ClH/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;1H/t11-;/m1./s1

HIDE SMILES / InChI

Molecular Formula C14H16N2O2
Molecular Weight 244.289
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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
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
Epileptiform seizures during prolonged etomidate sedation.
1983 Aug 27
Venous reactions following etomidate.
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
[Alfentanil in routine clinical use. A study of 50 patients].
1985 Jan
Etomidate versus thiopental for induction of anesthesia.
1985 Sep
[Increase in somatosensory evoked potentials during anesthesia induction with etomidate].
1986 Jun
Hypertension during anaesthesia with monoamine oxidase inhibitors.
1987 Jun
Angioneurotic oedema following etomidate/lignocaine.
1987 Mar
[Fentanyl in the prevention of etomidate-induced myoclonus].
1987 May-Jun
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
Generalised seizures after etomidate anaesthesia.
1988 Sep
Etomidate infusions for the control of refractory status epilepticus.
1989
[A new formulation of etomidate in lipid emulsion--bioavailability and venous provocation].
1989 Aug
Cardiovascular instability following bolus dose of etomidate.
1989 May
[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
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
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
An unexpected arousal effect of etomidate in a patient on high-dose steroids.
1998 Dec
Reducing myoclonus after etomidate.
1999 Jan
Myoclonus associated with etomidate for ED procedural sedation and analgesia.
2003 Nov
Comparison of etomidate and midazolam for prehospital rapid-sequence intubation.
2004 Jul-Sep
Double-blind placebo controlled study of the effects of etomidate-alfentanil anesthesia in electroconvulsive therapy.
2004 Jun
Contrasting anesthetic sensitivities of T-type Ca2+ channels of reticular thalamic neurons and recombinant Ca(v)3.3 channels.
2005 Jan
Magnesium sulfate pretreatment reduces myoclonus after etomidate.
2005 Sep
[Prevention of myoclonus after etomidate using a priming dose].
2006 Oct
Etomidate versus midazolam for procedural sedation in pediatric outpatients: a randomized controlled trial.
2006 Oct
Severe myoclonus prior to electroconvulsive therapy following intravenous etomidate.
2007 Apr
Randomized clinical trial of etomidate versus propofol for procedural sedation in the emergency department.
2007 Jan
Etomidate-induced pacemaker-mediated ventricular tachycardia.
2007 May
Fatal outcome during anaesthesia induction in a patient with amiodarone-induced thyrotoxicosis.
2008 Apr
A comparison of midazolam with remifentanil for the prevention of myoclonic movements following etomidate injection.
2008 Jan-Feb
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
Does lidocaine more effectively prevent pain upon induction with propofol or etomidate when given preemptively than when mixed with the drug?
2010 Nov
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.
Substance Class Chemical
Created
by admin
on Fri Dec 15 19:44:19 GMT 2023
Edited
by admin
on Fri Dec 15 19:44:19 GMT 2023
Record UNII
ZUM3W5027S
Record Status Validated (UNII)
Record Version
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Name Type Language
ETOMIDATE HYDROCHLORIDE
WHO-DD  
Common Name English
Etomidate hydrochloride [WHO-DD]
Common Name English
1H-IMIDAZOLE-5-CARBOXYLIC ACID, 1-(1-PHENYLETHYL)-, ETHYL ESTER, (R)-, HYDROCHLORIDE
Common Name English
Code System Code Type Description
EVMPD
SUB02046MIG
Created by admin on Fri Dec 15 19:44:19 GMT 2023 , Edited by admin on Fri Dec 15 19:44:19 GMT 2023
PRIMARY
ECHA (EC/EINECS)
258-423-3
Created by admin on Fri Dec 15 19:44:19 GMT 2023 , Edited by admin on Fri Dec 15 19:44:19 GMT 2023
PRIMARY
CAS
53188-20-8
Created by admin on Fri Dec 15 19:44:19 GMT 2023 , Edited by admin on Fri Dec 15 19:44:19 GMT 2023
PRIMARY
PUBCHEM
198290
Created by admin on Fri Dec 15 19:44:19 GMT 2023 , Edited by admin on Fri Dec 15 19:44:19 GMT 2023
PRIMARY
SMS_ID
100000088258
Created by admin on Fri Dec 15 19:44:19 GMT 2023 , Edited by admin on Fri Dec 15 19:44:19 GMT 2023
PRIMARY
FDA UNII
ZUM3W5027S
Created by admin on Fri Dec 15 19:44:19 GMT 2023 , Edited by admin on Fri Dec 15 19:44:19 GMT 2023
PRIMARY
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