METOMIDATE

Details

Stereochemistry	RACEMIC
Molecular Formula	C13H14N2O2
Molecular Weight	230.2625
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC(=O)C1=CN=CN1C(C)C2=CC=CC=C2

InChI

InChIKey=FHFZEKYDSVTYLL-UHFFFAOYSA-N

InChI=1S/C13H14N2O2/c1-10(11-6-4-3-5-7-11)15-9-14-8-12(15)13(16)17-2/h3-10H,1-2H3

HIDE SMILES / InChI

Description
Sources: http://www.vetpharm.uzh.ch/reloader.htm?tak/old/03000000/00037201.01?inhalt_c.htm
Curator's Comment: description was created based on several sources, including: https://www.fda.gov/AnimalVeterinary/DevelopmentApprovalProcess/MinorUseMinorSpecies/ucm164110.htm | https://www.drugs.com/vet/aquacalm-can.html | https://www.ncbi.nlm.nih.gov/pubmed/27003680

Metomidate is a non-barbiturate imidazole which produces a sleepy condition of 20-60 minutes duration without substantial analgesia. Since the beginning of 1997 the use of the hypnotic drug metomidate (Hypnodil) in swine is nor longer allowed. This ban caused a substantial therapeutic deficit for anesthesia in swine. 11C-metomidate may be used with positron emission tomography which can differentiate adrenocortical from nonadrenocortical tumors and a suspected adrenocortical cancer may be characterized and staged before surgery. Metomidate hydrochloride is for the sedation and anesthesia of aquarium and non-food fish species. Aquacalm has been granted Indexed status by the FDA for this purpose.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Cytochrome P450 2A5 3 Target ID: CHEMBL4085 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2573050	Inhibitor 8297	0.9 µM [Ki]
Cytochrome P450 11B1 9 Target ID: CHEMBL1908 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25871964	Inhibitor 8297
Cytochrome P450 11B2 6 Target ID: CHEMBL2722 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25871964	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Sleepy condition 2 Sources: http://www.vetpharm.uzh.ch/reloader.htm?tak/old/03000000/00037201.01?inhalt_c.htm	Primary		Withdrawn	Hypnodil Approved Use Unknown
Adrenocortical tumors 2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27003680	Diagnostic		Phase II 1132	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP11A1 6 CYP2C19 1478 CYP19A1 60 CYP11B1 10 MRP-1 2 CYP11B2 11 UMAT 3	P-gp 1537

Drug as perpetrator

Target	Modality	Activity
CYP3A4 1925	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=170466159	inconclusive [IC50 1.5487 uM]
CYP11A1 6	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/18397978/	likely
UMAT 3	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/602162#sid=850834	no [Inhibition 10 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/778#sid=850834	no [Inhibition 5 uM]
CYP19A1 60	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/743139#sid=144204539	no
MRP-1 2	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/799#sid=850834	no
CYP2C9 1819	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=170466159	yes [IC50 10.964 uM]
CYP11B2 12	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/18397978/	yes [IC50 16.7 uM]
CYP11B1 10	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/18397978/	yes [IC50 4.6 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=170466159	yes [IC50 7.7619 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1537	substrate 3367 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=144204539	no

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/588834#sid=124889791

PubMed

Title	Date	PubMed
The role of PET in localization of neuroendocrine and adrenocortical tumors.	2002 Sep	12381551
Pharmacokinetic and pharmacodynamic properties of metomidate in turbot (Scophthalmus maximus) and halibut (Hippoglossus hippoglossus).	2003 Apr	12667178
Comparison of three different purification methods for the routine preparation of [11C] Metomidate.	2003 Aug-Sep	12941500
11C-metomidate PET imaging of adrenocortical cancer.	2003 Mar	12634969
Imaging of adrenal incidentalomas with PET using (11)C-metomidate and (18)F-FDG.	2004 Jun	15181132
Positron emission tomography imaging of adrenal masses: (18)F-fluorodeoxyglucose and the 11beta-hydroxylase tracer (11)C-metomidate.	2004 Sep	15197504
Invasive versus noninvasive measurement of allergic and cholinergic airway responsiveness in mice.	2005 Nov 25	16309547
[11C]metomidate positron emission tomography of adrenocortical tumors in correlation with histopathological findings.	2006 Apr	16403816
Imaging of adrenocortical metastases with [11C]metomidate.	2006 Aug	16721573
Rates of cortisol increase and decrease in channel catfish and sunshine bass exposed to an acute confinement stressor.	2006 May	16466968
Vasopressin in septic shock: effects on pancreatic, renal, and hepatic blood flow.	2007	18078508
Do anesthetics and sampling strategies affect transcription analysis of fish tissues?	2007 Jun 8	17559653
PET in the diagnostic evaluation of adrenal tumors.	2007 Sep	17464268
Something old, something new, PET in adrenal imaging.	2008 Jul	18338165
[123 I]Iodometomidate for molecular imaging of adrenocortical cytochrome P450 family 11B enzymes.	2008 Jun	18397978
Cloning of somatolactin alpha, beta forms and the somatolactin receptor in Atlantic salmon: seasonal expression profile in pituitary and ovary of maturing female broodstock.	2008 Sep 15	18793397
Masked volume wise Principal Component Analysis of small adrenocortical tumours in dynamic [11C]-metomidate Positron Emission Tomography.	2009 Apr 22	19386097
Computed tomography, magnetic resonance imaging and 11C-metomidate positron emission tomography for evaluation of adrenal incidentalomas.	2009 Feb	18082990
(18)F-labelled metomidate analogues as adrenocortical imaging agents.	2009 May	19423012
Intestinal barrier function of Atlantic salmon (Salmo salar L.) post smolts is reduced by common sea cage environments and suggested as a possible physiological welfare indicator.	2010 Nov 9	21062437
Various aspects of piscine toxicology.	2010 Sep	21217882
11C-metomidate positron emission tomography after dexamethasone suppression for detection of small adrenocortical adenomas in primary aldosteronism.	2010 Sep	20644954
Anesthesia induces stress in Atlantic salmon (Salmo salar), Atlantic cod (Gadus morhua) and Atlantic halibut (Hippoglossus hippoglossus).	2010 Sep	19680764

Patents

Sample Use Guides

In Vivo Use Guide

Pigs below 50 kg body weight: Intraperitoneal 10 mg/kg Pigs over 50 kg body weight: Intravenous 4 mg/kg

Route of Administration: Other

In Vitro Use Guide

Ks-values for substrate binding spectra of metomidate from solubilized liver microsomes of control and pyrazole-treated D2 mice are 7.3 and 1.3 uM respectively.

Name

Type

Language

METOMIDATE

Official Name

English

METHOXYMOL

Common Name

English

(±)-METOMIDATE

Common Name

English

R-7315

Code

English

metomidate [INN]

Common Name

English

METOMIDATE [MI]

Common Name

English

METHYL 1-(.ALPHA.-METHYLBENZYL)IMIDAZOLE-5-CARBOXYLATE

Systematic Name

English

ETOMIDATE IMPURITY B [EP IMPURITY]

Common Name

English

ETOMIDATE IMPURITY, METOMIDATE- [USP IMPURITY]

Common Name

English

1H-IMIDAZOLE-5-CARBOXYLIC ACID, 1-(1-PHENYLETHYL)-, METHYL ESTER

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29756