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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-dimethylbarbituric acidNot 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 KeyInChIKey=UYXAWHWODHRRMR-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
    3'-OxohexobarbitalDetails
    3'-Oxohexobarbital
      Hexobarbital glutathione conjugate derivativeDetails
      Epoxy-hexobarbital
        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 solubility1.51e+00 g/lALOGPS
        logP1.8ALOGPS
        logP1.25ChemAxon
        logS-2.2ALOGPS
        pKa (strongest acidic)8.41ChemAxon
        physiological charge0ChemAxon
        hydrogen acceptor count3ChemAxon
        hydrogen donor count1ChemAxon
        polar surface area66.48ChemAxon
        rotatable bond count1ChemAxon
        refractivity61.95ChemAxon
        polarizability24.14ChemAxon
        number of rings2ChemAxon
        bioavailability1ChemAxon
        rule of fiveYesChemAxon
        Ghose filterYesChemAxon
        Veber's ruleNoChemAxon
        MDDR-like ruleNoChemAxon
        Spectra
        SpectraNot Available
        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

        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

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