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Identification
NameButethal
Accession NumberDB01353
TypeSmall Molecule
GroupsApproved, Illicit
Description

Butethal is a sedative and a hypnotic drug.

Structure
Thumb
Synonyms
SynonymLanguageCode
ButethalNot AvailableNot Available
ButobarbitalNot AvailableNot Available
ButobarbitoneNot AvailableNot Available
NeonalNot AvailableNot Available
Prescription ProductsNot Available
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International Brands
NameCompany
NeonalNot Available
SonerylNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
CAS number77-28-1
WeightAverage: 212.2456
Monoisotopic: 212.116092388
Chemical FormulaC10H16N2O3
InChI KeySTDBAQMTJLUMFW-UHFFFAOYSA-N
InChI
InChI=1S/C10H16N2O3/c1-3-5-6-10(4-2)7(13)11-9(15)12-8(10)14/h3-6H2,1-2H3,(H2,11,12,13,14,15)
IUPAC Name
5-butyl-5-ethyl-1,3-diazinane-2,4,6-trione
SMILES
CCCCC1(CC)C(=O)NC(=O)NC1=O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as barbituric acid derivatives. These are compounds containing a perhydropyrimidine ring substituted at C-2, -4 and -6 by oxo groups.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassDiazines
Sub ClassPyrimidines and pyrimidine derivatives
Direct ParentBarbituric acid derivatives
Alternative Parents
Substituents
  • Barbiturate
  • Ureide
  • 1,3-diazinane
  • Urea
  • Carboxamide group
  • Azacycle
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Aliphatic heteromonocyclic compound
Molecular FrameworkAliphatic heteromonocyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationFor the treatment of insomnia.
PharmacodynamicsButethal (also known as butobarbitone and butobarbital) belongs to a group of medicines called the barbiturates. It is thought to act on receptors in the brain (GABA receptors) causing the release of the chemical GABA. This chemical inhibits certain areas of the brain resulting in sleepiness.
Mechanism of actionButethal binds at a distinct binding site associated with a Cl- ionopore at the GABAA 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. All of these effects are associated with marked decreases in GABA-sensitive neuronal calcium conductance (gCa). The net result of barbiturate action is acute potentiation of inhibitory GABAergic tone. Barbiturates also act through potent (if less well characterized) and direct inhibition of excitatory AMPA-type glutamate receptors, resulting in a profound suppression of glutamatergic neurotransmission.
AbsorptionRapidly absorbed following oral administration.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Hepatic.

Route of eliminationNot Available
Half life37 hours
ClearanceNot Available
ToxicitySigns of overdose include confusion (severe), decrease in or loss of reflexes, drowsiness (severe), fever, irritability (continuing), low body temperature, poor judgment, shortness of breath or slow or troubled breathing, slow heartbeat, slurred speech, staggering, trouble in sleeping, unusual movements of the eyes, weakness (severe).
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9222
Blood Brain Barrier+0.9712
Caco-2 permeable-0.5923
P-glycoprotein substrateSubstrate0.601
P-glycoprotein inhibitor INon-inhibitor0.684
P-glycoprotein inhibitor IINon-inhibitor0.968
Renal organic cation transporterNon-inhibitor0.9116
CYP450 2C9 substrateNon-substrate0.7899
CYP450 2D6 substrateNon-substrate0.9146
CYP450 3A4 substrateNon-substrate0.739
CYP450 1A2 substrateNon-inhibitor0.9149
CYP450 2C9 substrateNon-inhibitor0.8109
CYP450 2D6 substrateNon-inhibitor0.9343
CYP450 2C19 substrateNon-inhibitor0.7678
CYP450 3A4 substrateNon-inhibitor0.9762
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9528
Ames testNon AMES toxic0.6449
CarcinogenicityNon-carcinogens0.8975
BiodegradationNot ready biodegradable0.947
Rat acute toxicity3.0258 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9709
hERG inhibition (predictor II)Non-inhibitor0.8922
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point128.5 °CPhysProp
water solubility4880 mg/L (at 25 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP1.73HANSCH,C ET AL. (1995)
logS-1.64ADME Research, USCD
pKa7.86SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility1.27 mg/mLALOGPS
logP1.65ALOGPS
logP1.61ChemAxon
logS-2.2ALOGPS
pKa (Strongest Acidic)8.48ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area75.27 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity53.45 m3·mol-1ChemAxon
Polarizability21.62 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
ATC CodesN05CA03
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AminophyllineThe barbiturate, butethal, decreases the effect of aminophylline.
BetamethasoneThe barbiturate, butethal, may decrease the effect of the corticosteroid, betamethasone.
ClomifeneThe enzyme inducer, butethal, decreases the effect of the hormone agent, clomifene.
Conjugated EstrogensThe enzyme inducer, butethal, decreases the effect of the hormone agent, conjugated estrogens.
CyclosporineThe barbiturate, butethal, increases the effect of cyclosporine.
DexamethasoneThe barbiturate, butethal, may decrease the effect of the corticosteroid, dexamethasone.
DiethylstilbestrolThe enzyme inducer, butethal, decreases the effect of the hormone agent, diethylstilbestrol.
DoxycyclineThe anticonvulsant, butethal, decreases the effect of doxycycline.
EstradiolThe enzyme inducer, butethal, decreases the effect of the hormone agent, estradiol.
Ethinyl EstradiolThis product may cause a slight decrease of contraceptive effect
FelodipineThe barbiturate, butethal, decreases the effect of felodipine.
FludrocortisoneThe barbiturate, butethal, may decrease the effect of the corticosteroid, fludrocortisone.
Folic AcidFolic acid decreases the effect of anticonvulsant, butethal.
GefitinibThe CYP3A4 inducer, butethal, may decrease the serum concentration and therapeutic effects of gefitinib.
GriseofulvinThe barbiturate, butethal, decreases the effect of griseofulvin.
HydrocortisoneThe barbiturate, butethal, may decrease the effect of the corticosteroid, hydrocortisone.
LevonorgestrelPhenobarbital decreases the effect of levonorgestrel
Medroxyprogesterone AcetateThe enzyme inducer, butethal, decreases the effect of the hormone agent, medroxyprogesterone.
Megestrol acetateThe enzyme inducer, butethal, decreases the effect of the hormone agent, megestrol.
MethadoneThe barbiturate, butethal, decreases the effect of methadone.
MetronidazoleThe barbiturate, butethal, decreases the effect of metronidazole.
NifedipineThe barbiturate, butethal, decreases the effect of the calcium channel blocker, nifedipine.
NorethindroneThis product may cause a slight decrease of contraceptive effect
OxtriphyllineThe barbiturate, butethal, decreases the effect of oxtriphylline.
PrednisoloneThe barbiturate, butethal, may decrease the effect of the corticosteroid, prednisolone.
PrednisoneThe barbiturate, butethal, may decrease the effect of the corticosteroid, prednisone.
QuinidineThe anticonvulsant, butethal, decreases the effect of quinidine.
TheophyllineThe barbiturate, butethal, decreases the effect of theophylline.
TriamcinoloneThe barbiturate, butethal, 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. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  6. 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
  7. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. 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

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Drug created on July 06, 2007 13:49 / Updated on February 04, 2014 20:44