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

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

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
Effect of premedication on etomidate anaesthesia.	1979 Dec	526383
Etomidate: a foreshortened clinical trial.	1980 Nov	7457821
The prevention of etomidate-induced myoclonus.	1984 Jan	6696228
Prolonged myoclonus after etomidate anesthesia.	1985 Jan	3966657
Etomidate versus thiopental for induction of anesthesia.	1985 Sep	4025853
Etomidate infusions for the control of refractory status epilepticus.	1989	2745868
[The modification of injection pain and the incidence of thrombophlebitis following etomidate].	1990 Jan	2178488
[Etomidate using a new solubilizer. Experimental clinical studies on venous tolerance and bioavailability].	1990 Oct	2278365
Total intravenous anesthesia for children undergoing brief diagnostic or therapeutic procedures.	1995 Jun	7546752
Midazolam pretreatment reduces etomidate-induced myoclonic movements.	2003 Feb	12635389
Deletion of the alpha1 or beta2 subunit of GABAA receptors reduces actions of alcohol and other drugs.	2003 Jan	12490572
Myoclonus associated with etomidate for ED procedural sedation and analgesia.	2003 Nov	14655236
Myoclonus after prolonged infusion of etomidate treated with dantrolene.	2003 Sep	14652121
BIS during etomidate-induced myoclonus.	2006 Apr	16548978
[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
Randomized clinical trial of etomidate versus propofol for procedural sedation in the emergency department.	2007 Jan	16997421
Pretreatment with dexmedetomidine or thiopental decreases myoclonus after etomidate: a randomized, double-blind controlled trial.	2010 Mar	20018300
Does lidocaine more effectively prevent pain upon induction with propofol or etomidate when given preemptively than when mixed with the drug?	2010 Nov	21056806
GABAA receptor open-state conformation determines non-competitive antagonist binding.	2011 Feb 1	21111751
Etomidate deteriorates the toxicity of advanced glycation end products to human endothelial Eahy926 cells.	2014	25421967
Prevention of etomidate-induced myoclonus: which is superior: Fentanyl, midazolam, or a combination? A Retrospective comparative study.	2014 Feb 16	24535067

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.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:34:08 GMT 2023` Edited by `admin` on `Fri Dec 15 15:34:08 GMT 2023`
Record UNII	Z22628B598
Record Status	`Validated (UNII)`
Record Version

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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