Etomidate hydrochloride

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 Search

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

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 2752		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 846		0.7 µM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pain 619 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/nda/99/018227_S012_AMIDATE_PRNTLBL.pdf	Primary		Approved 8583	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
2000 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3729056/ \| https://pubmed.ncbi.nlm.nih.gov/34060021/	0.48 mg/kg single, intravenous dose: 0.48 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		ETOMIDATE blood	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE 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
324 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3729056/ \| https://pubmed.ncbi.nlm.nih.gov/34060021/	0.48 mg/kg single, intravenous dose: 0.48 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		ETOMIDATE blood	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
25% REVIEW https://pubmed.ncbi.nlm.nih.gov/34060021/			ETOMIDATE plasma	Homo sapiens

Doses

Dose	Population	Adverse events
0.3 mg/kg single, intravenous Recommended Dose: 0.3 mg/kg Route: intravenous Route: single Dose: 0.3 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/19573904/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/19573904/	Sources: https://pubmed.ncbi.nlm.nih.gov/19573904/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
			inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP 110 CYP11B1 10 CYP11B2 11 CYP11A1 6 GLUT1 5		CYP17A1 3 CYP11A1 3

Drug as perpetrator

Target	Modality	Activity
CYP11A1 6	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/20352599/	no
CYP 150	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/3377236/	yes
CYP11A1 6	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/20352599/	yes
CYP11B1 10	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/20352599/	yes
CYP11B2 12	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/20352599/	yes
CYP17A1 3	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/20352599/	yes
GLUT1 20	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/10927023/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 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
BioCrick	BCC4255	http://www.biocrick.com/Etomidate-hydrochloride-BCC4255.html
BOC Sciences	53188-20-8	https://www.bocsci.com/etomidate-hydrochloride-cas-53188-20-8-item-474221.html
Chem Scene	CS-1834	http://www.chemscene.com/53188-20-8.html
Chemspace	CSSB00102527356	https://chem-space.com/CSSB00102527356
CSNpharm	CSN18321	https://www.csnpharm.com/products/etomidate-hydrochloride.html
eNovation Chemicals	D394223	https://www.enovationchem.com/ProductDetails.asp?ProductID=D394223
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

PubMed

Title	Date	PubMed
Prevention of etomidate-induced myoclonus: which is superior: Fentanyl, midazolam, or a combination? A Retrospective comparative study.	2014-02-16	24535067
Etomidate deteriorates the toxicity of advanced glycation end products to human endothelial Eahy926 cells.	2014	25421967
GABAA receptor open-state conformation determines non-competitive antagonist binding.	2011-02-01	21111751
Does lidocaine more effectively prevent pain upon induction with propofol or etomidate when given preemptively than when mixed with the drug?	2010-11	21056806
Reducing myoclonus after etomidate.	1999-01	9915320
An unexpected arousal effect of etomidate in a patient on high-dose steroids.	1998-12	9856742
Vascular effects of etomidate administered for electroencephalographic burst suppression in humans.	1998-10	9796607
Anesthesia sensitivity in mice that lack the beta3 subunit of the gamma-aminobutyric acid type A receptor.	1998-03	9523823
Cerebral hypoxia after etomidate administration and temporary cerebral artery occlusion.	1997-10	9322462
Propylene glycol toxicity caused by prolonged infusion of etomidate.	1995-10	8563446
Focal cerebral ischemia during anesthesia with etomidate, isoflurane, or thiopental: a comparison of the extent of cerebral injury.	1995-10	8559304
Propylene glycol toxicity following continuous etomidate infusion for the control of refractory cerebral edema.	1995-08	7477798
Total intravenous anesthesia for children undergoing brief diagnostic or therapeutic procedures.	1995-06	7546752
Acute toxicosis in two dogs associated with etomidate-propylene glycol infusion.	1994-12	7898032
Excitatory effects and electroencephalographic correlation of etomidate, thiopental, methohexital, and propofol.	1993-11	8214699
[Etomidate using a new solubilizer. Experimental clinical studies on venous tolerance and bioavailability].	1990-10	2278365
[Anesthesia for cardioversion. A comparison of propofol and etomidate].	1990-05-01	2207824
[The modification of injection pain and the incidence of thrombophlebitis following etomidate].	1990-01	2178488
[A new formulation of etomidate in lipid emulsion--bioavailability and venous provocation].	1989-08	2675669
Cardiovascular instability following bolus dose of etomidate.	1989-05	2742101
Etomidate infusions for the control of refractory status epilepticus.	1989	2745868
Generalised seizures after etomidate anaesthesia.	1988-09	3177871
Use of etomidate for elective cardioversion.	1988-04	3354919
Respiratory disturbance during recovery from etomidate anaesthesia.	1988-01	3344940
Vecuronium induced bradycardia following induction of anaesthesia with etomidate or thiopentone, with or without fentanyl.	1988-01	2892519
Hypertension during anaesthesia with monoamine oxidase inhibitors.	1987-06	3618996
[Fentanyl in the prevention of etomidate-induced myoclonus].	1987-05-01	3621016
Angioneurotic oedema following etomidate/lignocaine.	1987-03	3578739
[Increase in somatosensory evoked potentials during anesthesia induction with etomidate].	1986-06	3752481
[Increased tendency to seizures as affected by long-term infusions of etomidate in delirium tremens].	1985-09	4083468
Myoclonus on recovery from etomidate.	1985-09	4025859
Etomidate versus thiopental for induction of anesthesia.	1985-09	4025853
Prolonged myoclonus after etomidate anesthesia.	1985-01	3966657
[Alfentanil in routine clinical use. A study of 50 patients].	1985-01	3919609
Venous reactions following etomidate.	1984-08	6743462
Alfentanil in minor gynaecological surgery: use with etomidate and a comparison with halothane.	1984-08	6148025
Venous sequelae following the injection of etomidate or thiopentone i.v.	1984-02	6691878
The prevention of etomidate-induced myoclonus.	1984-01	6696228
Cardiac complications during use of etomidate.	1983-12	6362477
[Etomidate in Intralipid. A solution for pain-free injection].	1983-10	6650800
Epileptiform seizures during prolonged etomidate sedation.	1983-08-27	6136664
The safety of etomidate: a new intravenous anaesthetic induction agent.	1983-06	6322557
Pain and myoclonus during induction with etomidate. A double-blind, controlled evaluation of the influence of droperidol and fentanyl.	1981	7027723
Etomidate: a foreshortened clinical trial.	1980-11	7457821
Venous complications after intravenous injection of diazepam, flunitrazepam, thiopentone and etomidate.	1980-06	6108669
Effect of premedication on etomidate anaesthesia.	1979-12	526383
Comparison of etomidate in combination with fentanyl or diazepam, with thiopentone as an induction agent for general anaesthesia.	1979-12	526382
Etomidate in a new solvent. A clinical evaluation.	1977-11-01	339773
Respiratory effects of etomidate.	1977-03	20912
Total intravenous anesthesia with etomidate. III. Some observations in adults.	1977	612112

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 hydrochloride [WHO-DD]

Preferred Name

English

Etomidate hydrochloride

Common Name

English

(R)-Ethyl 1-(1-phenylethyl)-1H-imidazole-5-carboxylate hydrochloride

Systematic Name

English

1H-Imidazole-5-carboxylic acid, 1-[(1R)-1-phenylethyl]-, ethyl ester, hydrochloride (1:1)

Systematic Name

English

Code System Code Type Description

EVMPD

SUB02046MIG