METOMIDATE HYDROCHLORIDE

Details

Stereochemistry	RACEMIC
Molecular Formula	C13H14N2O2.ClH
Molecular Weight	266.723
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=NZEDTZKNEKPBGR-UHFFFAOYSA-N

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

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 8504	0.9 µM [Ki]
Cytochrome P450 11B1 9 Target ID: CHEMBL1908 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25871964	Inhibitor 8504
Cytochrome P450 11B2 6 Target ID: CHEMBL2722 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25871964	Inhibitor 8504

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Sleepy condition 2 Sources: http://www.vetpharm.uzh.ch/reloader.htm?tak/old/03000000/00037201.01?inhalt_c.htm	Primary		Withdrawn	Hypnodil Approved Use Unknown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 1147	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252	inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP11A1 6 CYP2C19 2057 CYP19A1 429 CYP11B1 10 MRP-1 2 CYP11B2 11 UMAT 30	P-gp 2052

Drug as perpetrator

Target	Modality	Activity
CYP3A4 2633	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=170466159	inconclusive [IC50 1.5487 uM]
CYP11A1 6	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/18397978/	likely
UMAT 30	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/602162#sid=850834	no [Inhibition 10 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/778#sid=850834	no [Inhibition 5 uM]
CYP19A1 430	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/743139#sid=144204539	no
MRP-1 2	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/799#sid=850834	no
CYP2C9 2497	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=170466159	yes [IC50 10.964 uM]
CYP11B2 12	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/18397978/	yes [IC50 16.7 uM]
CYP11B1 10	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/18397978/	yes [IC50 4.6 uM]
CYP2D6 2546	inhibitor 4027 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 2052	substrate 4014 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=144204539	no

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/588834#sid=124889791

PubMed

Title	Date	PubMed
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.	2010-11-09	21062437
Various aspects of piscine toxicology.	2010-09	21217882
11C-metomidate positron emission tomography after dexamethasone suppression for detection of small adrenocortical adenomas in primary aldosteronism.	2010-09	20644954
Anesthesia induces stress in Atlantic salmon (Salmo salar), Atlantic cod (Gadus morhua) and Atlantic halibut (Hippoglossus hippoglossus).	2010-09	19680764
(18)F-labelled metomidate analogues as adrenocortical imaging agents.	2009-05	19423012
Masked volume wise Principal Component Analysis of small adrenocortical tumours in dynamic [11C]-metomidate Positron Emission Tomography.	2009-04-22	19386097
Computed tomography, magnetic resonance imaging and 11C-metomidate positron emission tomography for evaluation of adrenal incidentalomas.	2009-02	18082990
Cloning of somatolactin alpha, beta forms and the somatolactin receptor in Atlantic salmon: seasonal expression profile in pituitary and ovary of maturing female broodstock.	2008-09-15	18793397
Something old, something new, PET in adrenal imaging.	2008-07	18338165
[123 I]Iodometomidate for molecular imaging of adrenocortical cytochrome P450 family 11B enzymes.	2008-06	18397978
PET in the diagnostic evaluation of adrenal tumors.	2007-09	17464268
Do anesthetics and sampling strategies affect transcription analysis of fish tissues?	2007-06-08	17559653
Vasopressin in septic shock: effects on pancreatic, renal, and hepatic blood flow.	2007	18078508
Imaging of adrenocortical metastases with [11C]metomidate.	2006-08	16721573
Rates of cortisol increase and decrease in channel catfish and sunshine bass exposed to an acute confinement stressor.	2006-05	16466968
[11C]metomidate positron emission tomography of adrenocortical tumors in correlation with histopathological findings.	2006-04	16403816
Invasive versus noninvasive measurement of allergic and cholinergic airway responsiveness in mice.	2005-11-25	16309547
Positron emission tomography imaging of adrenal masses: (18)F-fluorodeoxyglucose and the 11beta-hydroxylase tracer (11)C-metomidate.	2004-09	15197504
Imaging of adrenal incidentalomas with PET using (11)C-metomidate and (18)F-FDG.	2004-06	15181132
Comparison of three different purification methods for the routine preparation of [11C] Metomidate.	2003-08-28	12941500
Pharmacokinetic and pharmacodynamic properties of metomidate in turbot (Scophthalmus maximus) and halibut (Hippoglossus hippoglossus).	2003-04	12667178
11C-metomidate PET imaging of adrenocortical cancer.	2003-03	12634969
The role of PET in localization of neuroendocrine and adrenocortical tumors.	2002-09	12381551

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 HYDROCHLORIDE

Common Name

English

NSC-168403

Preferred Name

English

METOMIDATE HYDROCHLORIDE [USP-RS]

Common Name

English

METOMIDATE CHLORIDE

Common Name

English

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

Systematic Name

English

(±)-METOMIDATE HYDROCHLORIDE

Common Name

English

METOMIDATE HYDROCHLORIDE [USP IMPURITY]

Common Name

English

METOMIDATE HYDROCHLORIDE [MART.]

Common Name

English

Code System Code Type Description

CAS

35944-74-2