ETOMIDATE

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 Search

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
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/nda/99/018227_S012_AMIDATE_PRNTLBL.pdf
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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
GABA-A receptor; alpha-6/beta-3/gamma-2 6 Target ID: CHEMBL2095190 Sources: https://academic.oup.com/bjaed/article/6/2/49/305039/The-molecular-mechanisms-of-general-anaesthesia	Agonist 2678		23.0 µM [EC50]
GABA-A receptor; alpha-6/beta-3/gamma-2 6 Target ID: CHEMBL2095190 Sources: https://academic.oup.com/bjaed/article/6/2/49/305039/The-molecular-mechanisms-of-general-anaesthesia	Modulator 828		0.7 µM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pain 614 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/nda/99/018227_S012_AMIDATE_PRNTLBL.pdf	Primary		Approved 8429	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

C_max

Value	Dose	Co-administered	Analyte	Population
87 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9447861/	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

Value	Dose	Co-administered	Analyte	Population
3263 ng × min/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9447861/	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
75 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9447861/	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

CYP3A4	CYP2C9	CYP2D6	hERG
			inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP 111 CYP11B1 10 CYP11B2 11 CYP11A1 6 GLUT1 5		CYP17A1 3 CYP11A1 3

Drug as perpetrator

Target	Modality	Activity
CYP11A1 6	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/20352599/	no
CYP 147	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/3377236/	yes
CYP11A1 6	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/20352599/	yes
CYP11B1 10	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/20352599/	yes
CYP11B2 12	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/20352599/	yes
CYP17A1 3	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/20352599/	yes
GLUT1 15	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/10927023/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/29324898/

Sourcing

Vendor/Aggregator	ID	URL
AA Blocks	AA00DB3A	https://www.aablocks.com/goods/Goods/detail?id=AA00DB3A
AK Scientific, Inc. (AKSCI)	X5016	http://www.aksci.com/item_detail.php?cat=X5016
ApexBio Technology	B1246	http://www.apexbt.com/etomidate-hydrochloride.html
BOC Sciences	53188-20-8	https://www.bocsci.com/etomidate-hydrochloride-cas-53188-20-8-item-474221.html
BioCrick	BCC4255	http://www.biocrick.com/Etomidate-hydrochloride-BCC4255.html
CSNpharm	CSN18321	https://www.csnpharm.com/products/etomidate-hydrochloride.html
Chem Scene	CS-1834	http://www.chemscene.com/53188-20-8.html
Chemspace	CSSB00102527356	https://chem-space.com/CSSB00102527356
Lab Network	LN01343487	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01343487
MedChem Express	HY-B0100A	https://www.medchemexpress.com/etomidate-hydrochloride.html
MolPort	MolPort-006-130-018	https://www.molport.com/shop/molecule-link/MolPort-006-130-018
MuseChem	I003948	https://www.musechem.com/product/I003948.html
eNovation Chemicals	D394223	https://www.enovationchem.com/ProductDetails.asp?ProductID=D394223

PubMed

Title	Date	PubMed
Total intravenous anesthesia with etomidate. III. Some observations in adults.	1977	612112
Etomidate in a new solvent. A clinical evaluation.	1977 Nov-Dec	339773
Effect of premedication on etomidate anaesthesia.	1979 Dec	526383
Comparison of etomidate in combination with fentanyl or diazepam, with thiopentone as an induction agent for general anaesthesia.	1979 Dec	526382
Venous complications after intravenous injection of diazepam, flunitrazepam, thiopentone and etomidate.	1980 Jun	6108669
Etomidate: a foreshortened clinical trial.	1980 Nov	7457821
Pain and myoclonus during induction with etomidate. A double-blind, controlled evaluation of the influence of droperidol and fentanyl.	1981	7027723
Epileptiform seizures during prolonged etomidate sedation.	1983 Aug 27	6136664
Cardiac complications during use of etomidate.	1983 Dec	6362477
The safety of etomidate: a new intravenous anaesthetic induction agent.	1983 Jun	6322557
[Etomidate in Intralipid. A solution for pain-free injection].	1983 Oct	6650800
Venous reactions following etomidate.	1984 Aug	6743462
Alfentanil in minor gynaecological surgery: use with etomidate and a comparison with halothane.	1984 Aug	6148025
Venous sequelae following the injection of etomidate or thiopentone i.v.	1984 Feb	6691878
The prevention of etomidate-induced myoclonus.	1984 Jan	6696228
[Increased tendency to seizures as affected by long-term infusions of etomidate in delirium tremens].	1985 Sep	4083468
Myoclonus on recovery from etomidate.	1985 Sep	4025859
Etomidate versus thiopental for induction of anesthesia.	1985 Sep	4025853
Hypertension during anaesthesia with monoamine oxidase inhibitors.	1987 Jun	3618996
Respiratory disturbance during recovery from etomidate anaesthesia.	1988 Jan	3344940
Etomidate infusions for the control of refractory status epilepticus.	1989	2745868
[A new formulation of etomidate in lipid emulsion--bioavailability and venous provocation].	1989 Aug	2675669
Cardiovascular instability following bolus dose of etomidate.	1989 May	2742101
[Anesthesia for cardioversion. A comparison of propofol and etomidate].	1990 May-Jun	2207824
Excitatory effects and electroencephalographic correlation of etomidate, thiopental, methohexital, and propofol.	1993 Nov	8214699
Acute toxicosis in two dogs associated with etomidate-propylene glycol infusion.	1994 Dec	7898032
Propylene glycol toxicity following continuous etomidate infusion for the control of refractory cerebral edema.	1995 Aug	7477798
Total intravenous anesthesia for children undergoing brief diagnostic or therapeutic procedures.	1995 Jun	7546752
Propylene glycol toxicity caused by prolonged infusion of etomidate.	1995 Oct	8563446
Focal cerebral ischemia during anesthesia with etomidate, isoflurane, or thiopental: a comparison of the extent of cerebral injury.	1995 Oct	8559304
Cerebral hypoxia after etomidate administration and temporary cerebral artery occlusion.	1997 Oct	9322462
An unexpected arousal effect of etomidate in a patient on high-dose steroids.	1998 Dec	9856742
Anesthesia sensitivity in mice that lack the beta3 subunit of the gamma-aminobutyric acid type A receptor.	1998 Mar	9523823
Vascular effects of etomidate administered for electroencephalographic burst suppression in humans.	1998 Oct	9796607
Reducing myoclonus after etomidate.	1999 Jan	9915320
Magnesium sulfate pretreatment reduces myoclonus after etomidate.	2005 Sep	16115978
BIS during etomidate-induced myoclonus.	2006 Apr	16548978
Remifentanil pretreatment reduces myoclonus after etomidate.	2006 Mar	16563323
[Prevention of myoclonus after etomidate using a priming dose].	2006 Oct	17005362
Etomidate versus midazolam for procedural sedation in pediatric outpatients: a randomized controlled trial.	2006 Oct	16997680
Etomidate-Lipuro is associated with considerably less injection pain in children compared with propofol with added lidocaine.	2006 Oct	16914464
Severe myoclonus prior to electroconvulsive therapy following intravenous etomidate.	2007 Apr	17471876
Complete atrioventricular block following etomidate.	2007 Dec	18210663
Etomidate-induced pacemaker-mediated ventricular tachycardia.	2007 May	17457141
Low-dose intravenous midazolam reduces etomidate-induced myoclonus: a prospective, randomized study in patients undergoing elective cardioversion.	2007 Nov	17959958
Etomidate and unpredicted seizures during electroconvulsive therapy.	2007 Sep	17804993
Fatal outcome during anaesthesia induction in a patient with amiodarone-induced thyrotoxicosis.	2008 Apr	18334037
Cytotoxicity and decreased corticosterone production in adrenocortical Y-1 cells by 3-methylsulfonyl-DDE and structurally related molecules.	2009 Apr	18651133
Lidocaine pretreatment reduces the frequency and severity of myoclonus induced by etomidate.	2010 Apr	20108006
Etomidate deteriorates the toxicity of advanced glycation end products to human endothelial Eahy926 cells.	2014	25421967

Patents

Sample Use Guides

In Vivo Use Guide

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

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