HEXOBARBITAL SODIUM

US Previously Marketed

First marketed in 1933

Details

Stereochemistry	RACEMIC
Molecular Formula	C12H15N2O3.Na
Molecular Weight	258.2489
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[Na+].CN1C(=O)[N-]C(=O)C(C)(C1=O)C2=CCCCC2

InChI

InChIKey=SQMCFUSVGSBKFK-UHFFFAOYSA-M

InChI=1S/C12H16N2O3.Na/c1-12(8-6-4-3-5-7-8)9(15)13-11(17)14(2)10(12)16;/h6H,3-5,7H2,1-2H3,(H,13,15,17);/q;+1/p-1

HIDE SMILES / InChI

Description
Sources: https://www.drugbank.ca/drugs/DB01355
Curator's Comment: description was created based on several sources, including https://www.drugs.com/international/citopam.html | https://www.ncbi.nlm.nih.gov/pubmed/2458634 | https://www.ncbi.nlm.nih.gov/pubmed/7965056

Hexobarbital or hexobarbitone, (sold both in acid and sodium salt, brand name Evipan, and Tobinal), is a barbiturate derivative having hypnotic and sedative effects. It was used in the 1940s and 1950s as an agent for inducing anesthesia for surgery, as well as a rapid-acting, short-lasting hypnotic for general use, and has a relatively fast onset of effects and short duration of action. It was also used to murder women prisoners at Ravensbruck Concentration Camp. Modern barbiturates (such as Thiopental) has largely supplanted the use of hexobarbital as an anesthetic, as they allow for better control of the depth of anesthesia. Hexobarbital is still used in some scientific research. Hexobarbital binds at a distinct binding site associated with a Cl- ionophore at the GABA-A receptor, increasing the duration of time for which the Cl- ionophore is open. The post-synaptic inhibitory effect of GABA in the thalamus is, therefore, prolonged.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
GABA-A receptor; benzodiazepine site 38 Target ID: CHEMBL2109243 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7965056	Activator 1430

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pain 614 Sources: https://www.ncbi.nlm.nih.gov/pubmed/4692611	Primary		Approved 8429	Citopan Approved Use Unknown

T_1/2

Value	Dose	Analyte	Population
419 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1164825/	2.97 mg/kg single, intravenous dose: 2.97 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	HEXOBARBITAL blood	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
376 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1164825/	4.1 mg/kg single, intravenous dose: 4.1 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	HEXOBARBITAL blood	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
261 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1164825/	7.32 mg/kg single, intravenous dose: 7.32 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	HEXOBARBITAL blood	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
490 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1164825/	7.32 mg/kg single, intravenous dose: 7.32 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	HEXOBARBITAL blood	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
	substrate 1037

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP2C19 991

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2C19 991	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/17487889/	yes
CYP2C9 1037	substrate 3367 Sources: https://doi.org/10.1093/oxfordjournals.jbchem.a123445	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:5706	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:5706
eMolecules	538943	https://www.emolecules.com/cgi-bin/more?vid=538943

PubMed

Title	Date	PubMed
Interaction of the competitive AMPA receptor antagonist NBQX with hexobarbital.	1993 Sep	8255925
Interaction between flumazenil and the anesthetic effects of hexobarbital in the rat.	1995 Apr 10	7614008
Pentobarbital decreases the gamma-aminobutyric acidA receptor subunit gamma-2 long/short mRNA ratio by a mechanism distinct from receptor occupation.	1997 Oct	9336343
A study of the duration of acute tolerance induced with hexobarbital in male rats.	1998 Apr	9586853
Essential requirements for substrate binding affinity and selectivity toward human CYP2 family enzymes.	2003 Jan 1	12464242
[New aspects of hexobarbital metabolism: stereoselective metabolism, new metabolic pathway via GSH conjugation, and 3-hydroxyhexobarbital dehydrogenases].	2004 Dec	15577260
Antiglucocorticoid RU38486 reduces net protein catabolism in experimental acute renal failure.	2005 Feb 17	15715918
Enantioselective gas chromatographic separation of racemic N-alkylated barbiturates: application of C11-Chirasil-Dex as chiral stationary phase in GC.	2007 Sep 18	19662180
Sir Ivan Magill KCVO, DSc, MB, BCh, BAO, FRCS, FFARCS (Hon), FFARCSI (Hon), DA, (1888-1986).	2008 Sep	18956794
Ligand diversity of human and chimpanzee CYP3A4: activation of human CYP3A4 by lithocholic acid results from positive selection.	2009 Jun	19299527
Detection of ubiquityl-calmodulin conjugates with a novel high-molecular weight ubiquitylprotein-isopeptidase in rabbit tissues.	2010 Oct 25	21156402

Patents

Sample Use Guides

In Vivo Use Guide

3.571 to 7.142 mg/kg

Route of Administration: Intravenous

In Vitro Use Guide

Membranes were incubated with [35S]TBPS in 10 mM Na, K-phosphate buffer at 21°C for 60 min, in the presence or absence of Hexobarbital except for experiments on anion and cation effects. The reaction was terminated by filtration through a Whatman GF/B filter presoaked in 0.05% polyethyleneimine (so as to reduce [gammaS]TBPS binding to the filter) and washing twice with 5 ml of buffer solution. Specific [35S]TBPS binding was obtained by subtracting nonspecific binding obtained in the presence of 10 mkM gamma-BHC from total binding.

Name

Type

Language

HEXOBARBITAL SODIUM

Common Name

English

NSC-255103

Code

English

HEXOBARBITAL SODIUM SALT [MI]

Common Name

English

HEXOBARBITAL SODIUM [MART.]

Common Name

English

Hexobarbital sodium [WHO-DD]

Common Name

English

HEXOBARBITAL SODIUM SALT

Common Name

English

EVIPAL SODIUM

Brand Name

English

Classification Tree Code System Code

NCI_THESAURUS

C67084