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Identification
NameGlutethimide
Accession NumberDB01437
TypeSmall Molecule
GroupsApproved, Illicit
Description

A hypnotic and sedative. Its use has been largely superseded by other drugs. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
2-Ethyl-2-phenylglutarimideNot AvailableNot Available
DoridenNot AvailableNot Available
Prescription ProductsNot Available
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International Brands
NameCompany
DoridenU.S.V .
ElrodormNot Available
GlimidPolfa Pabianice
GlutethimidBalkanpharma
NoxyronNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
CAS number77-21-4
WeightAverage: 217.2637
Monoisotopic: 217.110278729
Chemical FormulaC13H15NO2
InChI KeyJMBQKKAJIKAWKF-UHFFFAOYSA-N
InChI
InChI=1S/C13H15NO2/c1-2-13(10-6-4-3-5-7-10)9-8-11(15)14-12(13)16/h3-7H,2,8-9H2,1H3,(H,14,15,16)
IUPAC Name
3-ethyl-3-phenylpiperidine-2,6-dione
SMILES
CCC1(CCC(=O)NC1=O)C1=CC=CC=C1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as phenylpiperidines. These are compounds containing a phenylpiperidine skeleton, which consists of a piperidine bound to a phenyl group.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassPiperidines
Sub ClassPhenylpiperidines
Direct ParentPhenylpiperidines
Alternative Parents
Substituents
  • Phenylpiperidine
  • Piperidinedione
  • Piperidinone
  • Dicarboximide
  • Delta-lactam
  • Benzenoid
  • Monocyclic benzene moiety
  • Carboxylic acid imide, n-unsubstituted
  • Carboxylic acid imide
  • Lactam
  • Carboxamide group
  • Azacycle
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationFor the treatment of insomnia.
PharmacodynamicsGlutethimide is a hypnotic sedative that was introduced in 1954 as a safe alternative to barbiturates to treat insomnia. Before long, however, it had become clear that glutethimide was just as likely to cause addiction and caused similarly severe withdrawal symptoms.
Mechanism of actionGlutethimide seems to be a GABA agonist which helps induced sedation. It also induces CYP 2D6. When taken with codeine, it enables the body to convert higher amounts of the codeine (higher than the average 5 - 10%) to morphine. The general sedative effect also adds to the power of the combination.
AbsorptionVariable
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Hepatic. Glutethimide is almost completely metabolized.

Route of eliminationglutethimide is inactivated by conjugation and the metabolites are excreted in urine, only 2% of the parent substance is excreted in urine, up to 2% of the dose has been reported to be found in the faeces.
Half life10-12 hours
ClearanceNot Available
ToxicityIn adults, death has been reported after 5 g. The usual lethal dose is 10 to 20g, although survival after a dose of 28 g has been reported.
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+0.9973
Blood Brain Barrier+0.996
Caco-2 permeable+0.5931
P-glycoprotein substrateSubstrate0.6677
P-glycoprotein inhibitor INon-inhibitor0.5334
P-glycoprotein inhibitor IINon-inhibitor0.9611
Renal organic cation transporterNon-inhibitor0.7747
CYP450 2C9 substrateNon-substrate0.7785
CYP450 2D6 substrateNon-substrate0.894
CYP450 3A4 substrateSubstrate0.5173
CYP450 1A2 substrateNon-inhibitor0.8856
CYP450 2C9 substrateNon-inhibitor0.9101
CYP450 2D6 substrateNon-inhibitor0.8664
CYP450 2C19 substrateNon-inhibitor0.8671
CYP450 3A4 substrateNon-inhibitor0.863
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8527
Ames testNon AMES toxic0.8254
CarcinogenicityNon-carcinogens0.8911
BiodegradationNot ready biodegradable0.9927
Rat acute toxicity2.5276 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9778
hERG inhibition (predictor II)Non-inhibitor0.7311
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point78-81Hoffmann, K. and Tagmann, E.; U.S. Patent 2,673,205; March 23, 1954; assigned to Ciba Pharmaceutical Products, Inc.
water solubility999 mg/L (at 30 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP1.90HANSCH,C ET AL. (1995)
logS-2.34ADME Research, USCD
pKa9.2SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility0.327 mg/mLALOGPS
logP1.89ALOGPS
logP2.13ChemAxon
logS-2.8ALOGPS
pKa (Strongest Acidic)11.69ChemAxon
pKa (Strongest Basic)-6.7ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area46.17 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity60.65 m3·mol-1ChemAxon
Polarizability23.15 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Download (9.43 KB)
SpectraNot Available
References
Synthesis Reference

Hoffmann, K. and Tagmann, E.; U.S. Patent 2,673,205; March 23, 1954; assigned to Ciba Pharmaceutical Products, Inc.

General ReferenceNot Available
External Links
ATC CodesN05CE01
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AcenocoumarolMay increase the metabolism of Vitamin K Antagonists.
Food Interactions
  • Avoid alcohol.
  • Take without regard to meals.

Targets

1. Gamma-aminobutyric acid receptor subunit alpha-1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

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

References:

  1. Skerritt JH, Johnston GA: Interactions of some anaesthetic, convulsant, and anticonvulsant drugs at GABA-benzodiazepine receptor-ionophore complexes in rat brain synaptosomal membranes. Neurochem Res. 1983 Oct;8(10):1351-62. Pubmed

2. GABA-A receptor (anion channel)

Kind: protein group

Organism: Human

Pharmacological action: yes

Actions: positive allosteric modulator

Components

Name UniProt ID Details
Gamma-aminobutyric acid receptor subunit alpha-1 P14867 Details
Gamma-aminobutyric acid receptor subunit alpha-2 P47869 Details
Gamma-aminobutyric acid receptor subunit alpha-3 P34903 Details
Gamma-aminobutyric acid receptor subunit alpha-4 P48169 Details
Gamma-aminobutyric acid receptor subunit alpha-5 P31644 Details
Gamma-aminobutyric acid receptor subunit alpha-6 Q16445 Details
Gamma-aminobutyric acid receptor subunit beta-1 P18505 Details
Gamma-aminobutyric acid receptor subunit beta-2 P47870 Details
Gamma-aminobutyric acid receptor subunit beta-3 P28472 Details
Gamma-aminobutyric acid receptor subunit delta O14764 Details
Gamma-aminobutyric acid receptor subunit epsilon P78334 Details
Gamma-aminobutyric acid receptor subunit gamma-1 Q8N1C3 Details
Gamma-aminobutyric acid receptor subunit gamma-2 P18507 Details
Gamma-aminobutyric acid receptor subunit gamma-3 Q99928 Details
Gamma-aminobutyric acid receptor subunit pi O00591 Details
Gamma-aminobutyric acid receptor subunit theta Q9UN88 Details

References:

  1. ChEMBL Compound Report Card (Accessed December 2013)

Enzymes

1. Cholesterol side-chain cleavage enzyme, mitochondrial

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cholesterol side-chain cleavage enzyme, mitochondrial P05108 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

2. Cytochrome P450 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

References:

  1. Pearson MW, Roberts CJ: Drug induction of hepatic enzymes in the elderly. Age Ageing. 1984 Sep;13(5):313-6. Pubmed
  2. Petik D, Acs N, Banhidy F, Czeizel AE: A study of the effects of large doses of glutethimide that were used for self-poisoning during pregnancy on human fetuses. Toxicol Ind Health. 2008 Feb-Mar;24(1-2):69-78. Pubmed

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Drug created on July 26, 2007 13:33 / Updated on April 25, 2014 13:26