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Identification
NameHexobarbital
Accession NumberDB01355  (EXPT03301)
TypeSmall Molecule
GroupsApproved
Description

A barbiturate that is effective as a hypnotic and sedative. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
5-(1-Cyclohexen-1-yl)-1,5-dimethyl-2,4,6(1H,3H,5H)-pyrimidinetrioneNot AvailableNot Available
5-(1-cyclohexen-1-yl)-1,5-dimethylbarbituric acidNot AvailableNot Available
5-Cyclohex-1-enyl-1,5-dimethyl-pyrimidine-2,4,6-trioneNot AvailableNot Available
EvipanNot AvailableNot Available
HexobarbitalNot AvailableNot Available
HexobarbitoneNot AvailableNot Available
MethexenylNot AvailableNot Available
MethylhexabitalNot AvailableNot Available
Salts
Name/CAS Structure Properties
Hexobarbital sodium
Thumb Not applicable DBSALT000914
Brand names
NameCompany
EvipalNot Available
EvipanNot Available
TobinalNot Available
Brand mixturesNot Available
Categories
CAS number56-29-1
WeightAverage: 236.267
Monoisotopic: 236.116092388
Chemical FormulaC12H16N2O3
InChI KeyUYXAWHWODHRRMR-UHFFFAOYSA-N
InChI
InChI=1S/C12H16N2O3/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)
IUPAC Name
5-(cyclohex-1-en-1-yl)-1,5-dimethyl-1,3-diazinane-2,4,6-trione
SMILES
CN1C(=O)NC(=O)C(C)(C1=O)C1=CCCCC1
Mass Specshow(9.16 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassDiazines
SubclassPyrimidines and Pyrimidine Derivatives
Direct parentBarbituric Acid Derivatives
Alternative parentsUreides; Diazinanes; N-substituted Carboxylic Acid Imides; Tertiary Carboxylic Acid Amides; N-unsubstituted Carboxylic Acid Imides; Tertiary Amines; Secondary Carboxylic Acid Amides; Polyamines; Carboxylic Acids
Substituentsureide; 1,3-diazinane; carboxylic acid imide, n-substituted; tertiary carboxylic acid amide; carboxylic acid imide, n-unsubstituted; tertiary amine; carboxamide group; secondary carboxylic acid amide; carboxylic acid derivative; polyamine; carboxylic acid; amine; organonitrogen compound
Classification descriptionThis compound belongs to the barbituric acid derivatives. These are compounds containing a perhydropyrimidine ring substituted at C-2, -4 and -6 by oxo groups.
Pharmacology
IndicationFor the induction of anesthesia prior to the use of other general anesthetic agents and for induction of anesthesia for short surgical, diagnostic, or therapeutic procedures associated with minimal painful stimuli.
PharmacodynamicsHexobarbital is a barbiturate derivative having hypnotic and sedative effects. It was used in the 1940s-1950s as an agent for inducing anesthesia for surgery and has a relatively fast onset of effects and short duration of action. However it can be difficult to control the depth of anesthesia with hexobarbital which makes it quite dangerous, and it has now been replaced by safer drugs in human medicine, usually thiopental would be the barbiturate of choice for this application these days.
Mechanism of actionHexobarbital binds at a distinct binding site associated with a Cl- ionopore at the GABA-A receptor, increasing the duration of time for which the Cl- ionopore is open. The post-synaptic inhibitory effect of GABA in the thalamus is, therefore, prolonged.
AbsorptionNot Available
Volume of distributionNot Available
Protein binding25%
Metabolism

Hepatic.

SubstrateEnzymesProduct
Hexobarbital
3'-HydroxyhexobarbitalDetails
Hexobarbital
Epoxy-hexobarbitalDetails
3'-Hydroxyhexobarbital
Not Available
3'-OxohexobarbitalDetails
3'-Oxohexobarbital
Not Available
Hexobarbital glutathione conjugate derivativeDetails
Epoxy-hexobarbital
Not Available
Hexobarbital dihydrodiol derivativeDetails
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicitySymptoms of an overdose typically include sluggishness, incoordination, difficulty in thinking, slowness of speech, faulty judgment, drowsiness or coma, shallow breathing, staggering, and in severe cases coma and death.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9793
Blood Brain Barrier + 0.9649
Caco-2 permeable + 0.519
P-glycoprotein substrate Substrate 0.5562
P-glycoprotein inhibitor I Inhibitor 0.7705
P-glycoprotein inhibitor II Non-inhibitor 0.8379
Renal organic cation transporter Non-inhibitor 0.7687
CYP450 2C9 substrate Non-substrate 0.7622
CYP450 2D6 substrate Non-substrate 0.894
CYP450 3A4 substrate Non-substrate 0.543
CYP450 1A2 substrate Non-inhibitor 0.7994
CYP450 2C9 substrate Inhibitor 0.5316
CYP450 2D6 substrate Non-inhibitor 0.9369
CYP450 2C19 substrate Non-inhibitor 0.6349
CYP450 3A4 substrate Non-inhibitor 0.9571
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8803
Ames test Non AMES toxic 0.7061
Carcinogenicity Non-carcinogens 0.8753
Biodegradation Not ready biodegradable 0.9143
Rat acute toxicity 2.5050 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9348
hERG inhibition (predictor II) Non-inhibitor 0.8502
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
TabletOral250 mg
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point146.5 °CPhysProp
water solubility435 mg/L (at 25 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP1.98SANGSTER (1994)
logS-2.74ADME Research, USCD
pKa8.2SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility1.51ALOGPS
logP1.8ALOGPS
logP1.25ChemAxon
logS-2.2ALOGPS
pKa (Strongest Acidic)8.41ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area66.48 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity61.95 m3·mol-1ChemAxon
Polarizability24.14 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectra1D NMR
References
Synthesis ReferenceNot Available
General Reference
  1. Takenoshita R, Toki S: [New aspects of hexobarbital metabolism: stereoselective metabolism, new metabolic pathway via GSH conjugation, and 3-hydroxyhexobarbital dehydrogenases] Yakugaku Zasshi. 2004 Dec;124(12):857-71. Pubmed
  2. Wahlstrom G: A study of the duration of acute tolerance induced with hexobarbital in male rats. Pharmacol Biochem Behav. 1998 Apr;59(4):945-8. Pubmed
  3. Korkmaz S, Ljungblad E, Wahlstrom G: Interaction between flumazenil and the anesthetic effects of hexobarbital in the rat. Brain Res. 1995 Apr 10;676(2):371-7. Pubmed
  4. Dall V, Orntoft U, Schmidt A, Nordholm L: Interaction of the competitive AMPA receptor antagonist NBQX with hexobarbital. Pharmacol Biochem Behav. 1993 Sep;46(1):73-6. Pubmed
External Links
ResourceLink
KEGG DrugD01071
KEGG CompoundC11723
ChEBI5706
ChEMBLCHEMBL7728
Therapeutic Targets DatabaseDAP000688
PharmGKBPA449875
WikipediaHexobarbital
ATC CodesN05CA16N01AF02
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AminophyllineThe barbiturate, hexobarbital, decreases the effect of aminophylline.
BetamethasoneThe barbiturate, hexobarbital, may decrease the effect of the corticosteroid, betamethasone.
ClomifeneThe enzyme inducer, hexobarbital, decreases the effect of the hormone agent, clomifene.
Conjugated EstrogensThe enzyme inducer, hexobarbital, decreases the effect of the hormone agent, conjugated estrogens.
CyclosporineThe barbiturate, hexobarbital, increases the effect of cyclosporine.
DexamethasoneThe barbiturate, hexobarbital, may decrease the effect of the corticosteroid, dexamethasone.
DiethylstilbestrolThe enzyme inducer, hexobarbital, decreases the effect of the hormone agent, diethylstilbestrol.
DoxycyclineThe anticonvulsant, hexobarbital, decreases the effect of doxycycline.
EstradiolThe enzyme inducer, hexobarbital, decreases the effect of the hormone agent, estradiol.
Ethinyl EstradiolThis product may cause a slight decrease of contraceptive effect
FelodipineThe barbiturate, hexobarbital, decreases the effect of felodipine.
FludrocortisoneThe barbiturate, hexobarbital, may decrease the effect of the corticosteroid, fludrocortisone.
Folic AcidFolic acid decreases the effect of anticonvulsant, hexobarbital.
GefitinibThe CYP3A4 inducer, hexobarbital, may decrease the serum concentration and therapeutic effects of gefitinib.
GriseofulvinThe barbiturate, hexobarbital, decreases the effect of griseofulvin.
HydrocortisoneThe barbiturate, hexobarbital, may decrease the effect of the corticosteroid, hydrocortisone.
LevonorgestrelPhenobarbital decreases the effect of levonorgestrel
Medroxyprogesterone AcetateThe enzyme inducer, hexobarbital, decreases the effect of the hormone agent, medroxyprogesterone.
Megestrol acetateThe enzyme inducer, hexobarbital, decreases the effect of the hormone agent, megestrol.
MethadoneThe barbiturate, hexobarbital, decreases the effect of methadone.
MetronidazoleThe barbiturate, hexobarbital, decreases the effect of metronidazole.
NifedipineThe barbiturate, hexobarbital, decreases the effect of the calcium channel blocker, nifedipine.
NorethindroneThis product may cause a slight decrease of contraceptive effect
OxtriphyllineThe barbiturate, hexobarbital, decreases the effect of oxtriphylline.
PrednisoloneThe barbiturate, hexobarbital, may decrease the effect of the corticosteroid, prednisolone.
PrednisoneThe barbiturate, hexobarbital, may decrease the effect of the corticosteroid, prednisone.
QuinidineThe anticonvulsant, hexobarbital, decreases the effect of quinidine.
TheophyllineThe barbiturate, hexobarbital, decreases the effect of theophylline.
TriamcinoloneThe barbiturate, hexobarbital, may decrease the effect of the corticosteroid, triamcinolone.
Food InteractionsNot Available

Targets

1. Gamma-aminobutyric acid receptor subunit alpha-1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: potentiator

Components

Name UniProt ID Details
Gamma-aminobutyric acid receptor subunit alpha-1 P14867 Details

References:

  1. Whiting PJ: The GABAA receptor gene family: new opportunities for drug development. Curr Opin Drug Discov Devel. 2003 Sep;6(5):648-57. Pubmed
  2. Mehta AK, Ticku MK: An update on GABAA receptors. Brain Res Brain Res Rev. 1999 Apr;29(2-3):196-217. Pubmed
  3. Yamakura T, Bertaccini E, Trudell JR, Harris RA: Anesthetics and ion channels: molecular models and sites of action. Annu Rev Pharmacol Toxicol. 2001;41:23-51. Pubmed
  4. Krasowski MD, Harrison NL: General anaesthetic actions on ligand-gated ion channels. Cell Mol Life Sci. 1999 Aug 15;55(10):1278-303. Pubmed
  5. Tomlin SL, Jenkins A, Lieb WR, Franks NP: Preparation of barbiturate optical isomers and their effects on GABA receptors. Anesthesiology. 1999 Jun;90(6):1714-22. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  7. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  8. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

2. Gamma-aminobutyric acid receptor subunit alpha-2

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: potentiator

Components

Name UniProt ID Details
Gamma-aminobutyric acid receptor subunit alpha-2 P47869 Details

References:

  1. Yamakura T, Bertaccini E, Trudell JR, Harris RA: Anesthetics and ion channels: molecular models and sites of action. Annu Rev Pharmacol Toxicol. 2001;41:23-51. Pubmed
  2. Mehta AK, Ticku MK: An update on GABAA receptors. Brain Res Brain Res Rev. 1999 Apr;29(2-3):196-217. Pubmed

3. Gamma-aminobutyric acid receptor subunit alpha-3

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: potentiator

Components

Name UniProt ID Details
Gamma-aminobutyric acid receptor subunit alpha-3 P34903 Details

References:

  1. Yamakura T, Bertaccini E, Trudell JR, Harris RA: Anesthetics and ion channels: molecular models and sites of action. Annu Rev Pharmacol Toxicol. 2001;41:23-51. Pubmed
  2. Mehta AK, Ticku MK: An update on GABAA receptors. Brain Res Brain Res Rev. 1999 Apr;29(2-3):196-217. Pubmed

4. Gamma-aminobutyric acid receptor subunit alpha-4

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: potentiator

Components

Name UniProt ID Details
Gamma-aminobutyric acid receptor subunit alpha-4 P48169 Details

References:

  1. Mehta AK, Ticku MK: An update on GABAA receptors. Brain Res Brain Res Rev. 1999 Apr;29(2-3):196-217. Pubmed

5. Gamma-aminobutyric acid receptor subunit alpha-5

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: potentiator

Components

Name UniProt ID Details
Gamma-aminobutyric acid receptor subunit alpha-5 P31644 Details

References:

  1. Yamakura T, Bertaccini E, Trudell JR, Harris RA: Anesthetics and ion channels: molecular models and sites of action. Annu Rev Pharmacol Toxicol. 2001;41:23-51. Pubmed
  2. Mehta AK, Ticku MK: An update on GABAA receptors. Brain Res Brain Res Rev. 1999 Apr;29(2-3):196-217. Pubmed

6. Gamma-aminobutyric acid receptor subunit alpha-6

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: potentiator

Components

Name UniProt ID Details
Gamma-aminobutyric acid receptor subunit alpha-6 Q16445 Details

References:

  1. Mehta AK, Ticku MK: An update on GABAA receptors. Brain Res Brain Res Rev. 1999 Apr;29(2-3):196-217. Pubmed
  2. Yamakura T, Bertaccini E, Trudell JR, Harris RA: Anesthetics and ion channels: molecular models and sites of action. Annu Rev Pharmacol Toxicol. 2001;41:23-51. Pubmed

7. Neuronal acetylcholine receptor subunit alpha-4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Neuronal acetylcholine receptor subunit alpha-4 P43681 Details

References:

  1. Yamakura T, Bertaccini E, Trudell JR, Harris RA: Anesthetics and ion channels: molecular models and sites of action. Annu Rev Pharmacol Toxicol. 2001;41:23-51. Pubmed
  2. Arias HR, Bhumireddy P: Anesthetics as chemical tools to study the structure and function of nicotinic acetylcholine receptors. Curr Protein Pept Sci. 2005 Oct;6(5):451-72. Pubmed
  3. Krasowski MD, Harrison NL: General anaesthetic actions on ligand-gated ion channels. Cell Mol Life Sci. 1999 Aug 15;55(10):1278-303. Pubmed

8. Neuronal acetylcholine receptor subunit alpha-7

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Neuronal acetylcholine receptor subunit alpha-7 P36544 Details

References:

  1. Yamakura T, Bertaccini E, Trudell JR, Harris RA: Anesthetics and ion channels: molecular models and sites of action. Annu Rev Pharmacol Toxicol. 2001;41:23-51. Pubmed
  2. Arias HR, Bhumireddy P: Anesthetics as chemical tools to study the structure and function of nicotinic acetylcholine receptors. Curr Protein Pept Sci. 2005 Oct;6(5):451-72. Pubmed
  3. Krasowski MD, Harrison NL: General anaesthetic actions on ligand-gated ion channels. Cell Mol Life Sci. 1999 Aug 15;55(10):1278-303. Pubmed

9. Glutamate receptor 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Glutamate receptor 2 P42262 Details

References:

  1. Yamakura T, Bertaccini E, Trudell JR, Harris RA: Anesthetics and ion channels: molecular models and sites of action. Annu Rev Pharmacol Toxicol. 2001;41:23-51. Pubmed
  2. Krasowski MD, Harrison NL: General anaesthetic actions on ligand-gated ion channels. Cell Mol Life Sci. 1999 Aug 15;55(10):1278-303. Pubmed

10. Glutamate receptor ionotropic, kainate 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Glutamate receptor ionotropic, kainate 2 Q13002 Details

References:

  1. Yamakura T, Bertaccini E, Trudell JR, Harris RA: Anesthetics and ion channels: molecular models and sites of action. Annu Rev Pharmacol Toxicol. 2001;41:23-51. Pubmed
  2. Krasowski MD, Harrison NL: General anaesthetic actions on ligand-gated ion channels. Cell Mol Life Sci. 1999 Aug 15;55(10):1278-303. Pubmed

Enzymes

1. Cytochrome P450 2C19

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2C19 P33261 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  3. Adedoyin A, Prakash C, O’Shea D, Blair IA, Wilkinson GR: Stereoselective disposition of hexobarbital and its metabolites: relationship to the S-mephenytoin polymorphism in Caucasian and Chinese subjects. Pharmacogenetics. 1994 Feb;4(1):27-38. Pubmed
  4. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  5. Lewis DF, Modi S, Dickins M: Structure-activity relationship for human cytochrome P450 substrates and inhibitors. Drug Metab Rev. 2002 Feb-May;34(1-2):69-82. Pubmed

2. Cytochrome P450 2C9

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2C9 P11712 Details

References:

  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

3. Prostaglandin G/H synthase 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Prostaglandin G/H synthase 1 P23219 Details

References:

  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed

4. Cytochrome P450 2E1

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Cytochrome P450 2E1 P05181 Details

References:

  1. Ono S, Hatanaka T, Hotta H, Satoh T, Gonzalez FJ, Tsutsui M: Specificity of substrate and inhibitor probes for cytochrome P450s: evaluation of in vitro metabolism using cDNA-expressed human P450s and human liver microsomes. Xenobiotica. 1996 Jul;26(7):681-93. Pubmed

5. Cytochrome P450 1A2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 1A2 P05177 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

6. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

Comments
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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:14