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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 Its use has been largely superseded by other drugs.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
SynonymsNot Available
SaltsNot Available
Brand names
NameCompany
DoridenU.S.V .
ElrodormNot Available
GlimidPolfa Pabianice
GlutethimidBalkanpharma
NoxyronNot Available
Brand mixturesNot 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
Mass Specshow(9.43 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassPiperidines
SubclassPhenylpiperidines
Direct parentPhenylpiperidines
Alternative parentsPiperidinediones; Delta Lactams; Benzene and Substituted Derivatives; N-unsubstituted Carboxylic Acid Imides; Secondary Carboxylic Acid Amides; Carboxylic Acids; Polyamines
Substituentspiperidinedione; delta-lactam; piperidinone; benzene; carboxylic acid imide; carboxylic acid imide, n-unsubstituted; carboxamide group; secondary carboxylic acid amide; lactam; carboxylic acid derivative; carboxylic acid; polyamine; organonitrogen compound
Classification descriptionThis compound belongs to the phenylpiperidines. These are compounds containing a phenylpiperidine skeleton, which consists of a piperidine bound to a phenyl group.
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
Property Value Probability
Human Intestinal Absorption + 0.9973
Blood Brain Barrier + 0.996
Caco-2 permeable + 0.5931
P-glycoprotein substrate Substrate 0.6677
P-glycoprotein inhibitor I Non-inhibitor 0.5334
P-glycoprotein inhibitor II Non-inhibitor 0.9611
Renal organic cation transporter Non-inhibitor 0.7747
CYP450 2C9 substrate Non-substrate 0.7785
CYP450 2D6 substrate Non-substrate 0.894
CYP450 3A4 substrate Substrate 0.5173
CYP450 1A2 substrate Non-inhibitor 0.8856
CYP450 2C9 substrate Non-inhibitor 0.9101
CYP450 2D6 substrate Non-inhibitor 0.8664
CYP450 2C19 substrate Non-inhibitor 0.8671
CYP450 3A4 substrate Non-inhibitor 0.863
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8527
Ames test Non AMES toxic 0.8254
Carcinogenicity Non-carcinogens 0.8911
Biodegradation Not ready biodegradable 0.9927
Rat acute toxicity 2.5276 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9778
hERG inhibition (predictor II) Non-inhibitor 0.7311
Pharmacoeconomics
Manufacturers
  • Sanofi aventis us llc
  • Halsey drug co inc
  • Lannett co inc
  • Sandoz inc
  • Ucb inc
  • Vitarine pharmaceuticals inc
  • Watson laboratories inc
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 solubility3.27e-01 g/lALOGPS
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 area46.17ChemAxon
rotatable bond count2ChemAxon
refractivity60.65ChemAxon
polarizability23.15ChemAxon
number of rings2ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
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
ResourceLink
KEGG DrugD00532
KEGG CompoundC07489
PubChem Compound3487
PubChem Substance46506283
ChemSpider3367
Therapeutic Targets DatabaseDAP001305
PharmGKBPA164749505
WikipediaGlutethimide
ATC CodesN05CE01
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AcenocoumarolGlutethimide may decrease the anticoagulant effect of acenocoumarol.
AnisindioneGlutethimide may decrease the anticoagulant effect of anisindione.
DicoumarolGlutethimide may decrease the anticoagulant effect of dicumarol.
DonepezilPossible antagonism of action
GalantaminePossible antagonism of action
RivastigminePossible antagonism of action
TriprolidineThe CNS depressants, Triprolidine and Glutethimide, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
WarfarinGlutethimide may decrease the serum concentration of warfarin by increasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of warfarin if glutethimide is initiated, discontinued or dose changed.
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