ETOMIDATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C14H16N2O2
Molecular Weight	244.2896
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCOC(=O)c1cncn1[C@]([H])(C)c2ccccc2

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 4 Target ID: CHEMBL2095190 Sources: https://academic.oup.com/bjaed/article/6/2/49/305039/The-molecular-mechanisms-of-general-anaesthesia	Agonist 2456		23.0 µM [EC50]
GABA-A receptor; alpha-6/beta-3/gamma-2 4 Target ID: CHEMBL2095190 Sources: https://academic.oup.com/bjaed/article/6/2/49/305039/The-molecular-mechanisms-of-general-anaesthesia	Modulator 777		0.7 µM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pain 580 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/nda/99/018227_S012_AMIDATE_PRNTLBL.pdf	Primary		Approved 7997	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 4.00204792E11

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 1360

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP 97 CYP11B1 8 CYP11B2 9 CYP11A1 4 GLUT1 3		CYP17A1 3 CYP11A1 3

Drug as perpetrator

Target	Modality	Activity
CYP11A1 4	inducer 1333 Sources: https://pubmed.ncbi.nlm.nih.gov/20352599/	no
CYP 131	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/3377236/	yes
CYP11A1 4	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/20352599/	yes
CYP11B1 8	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/20352599/	yes
CYP11B2 9	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/20352599/	yes
CYP17A1 3	inducer 1333 Sources: https://pubmed.ncbi.nlm.nih.gov/20352599/	yes
GLUT1 13	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/10927023/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1392	inhibitor 1374 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
Respiratory effects of etomidate.	1977 Mar	20912
Etomidate in a new solvent. A clinical evaluation.	1977 Nov-Dec	339773
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
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
Alfentanil in minor gynaecological surgery: use with etomidate and a comparison with halothane.	1984 Aug	6148025
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
[Increase in somatosensory evoked potentials during anesthesia induction with etomidate].	1986 Jun	3752481
[Fentanyl in the prevention of etomidate-induced myoclonus].	1987 May-Jun	3621016
Use of etomidate for elective cardioversion.	1988 Apr	3354919
Respiratory disturbance during recovery from etomidate anaesthesia.	1988 Jan	3344940
Generalised seizures after etomidate anaesthesia.	1988 Sep	3177871
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
[The modification of injection pain and the incidence of thrombophlebitis following etomidate].	1990 Jan	2178488
Excitatory effects and electroencephalographic correlation of etomidate, thiopental, methohexital, and propofol.	1993 Nov	8214699
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
Cerebral hypoxia after etomidate administration and temporary cerebral artery occlusion.	1997 Oct	9322462
Anesthesia sensitivity in mice that lack the beta3 subunit of the gamma-aminobutyric acid type A receptor.	1998 Mar	9523823
Pretreatment with sufentanil reduces myoclonus after etomidate.	2003 Apr	12694150
A single M1 residue in the beta2 subunit alters channel gating of GABAA receptor in anesthetic modulation and direct activation.	2003 Oct 31	12939268
Double-blind placebo controlled study of the effects of etomidate-alfentanil anesthesia in electroconvulsive therapy.	2004 Jun	15167427
Midazolam is more likely to cause hypotension than etomidate in emergency department rapid sequence intubation.	2004 Nov	15496697
Contrasting anesthetic sensitivities of T-type Ca2+ channels of reticular thalamic neurons and recombinant Ca(v)3.3 channels.	2005 Jan	15644869
Magnesium sulfate pretreatment reduces myoclonus after etomidate.	2005 Sep	16115978
BIS during etomidate-induced myoclonus.	2006 Apr	16548978
Alpha5GABAA receptors mediate the amnestic but not sedative-hypnotic effects of the general anesthetic etomidate.	2006 Apr 5	16597725
Remifentanil pretreatment reduces myoclonus after etomidate.	2006 Mar	16563323
[Prevention of myoclonus after etomidate using a priming dose].	2006 Oct	17005362
Etomidate-Lipuro is associated with considerably less injection pain in children compared with propofol with added lidocaine.	2006 Oct	16914464
Complete atrioventricular block following etomidate.	2007 Dec	18210663
Randomized clinical trial of etomidate versus propofol for procedural sedation in the emergency department.	2007 Jan	16997421
Etomidate-induced pacemaker-mediated ventricular tachycardia.	2007 May	17457141
Fatal outcome during anaesthesia induction in a patient with amiodarone-induced thyrotoxicosis.	2008 Apr	18334037
Cardiovascular manifestations of sedatives and analgesics in the critical care unit.	2009 Jul-Aug	19092649
Lidocaine pretreatment reduces the frequency and severity of myoclonus induced by etomidate.	2010 Apr	20108006
Epileptic seizure during anaesthesia induction with etomidate.	2010 Jun	20803863
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.

Name

Type

Language

ETOMIDATE

Official Name

English

AMIDATE

Brand Name

English

ETOMIDATE [WHO-DD]

Common 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

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