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targets (1) enzymes (2)
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Identification
Name Glutethimide
Accession Number DB01437
Type small molecule
Groups illicit, approved
Description

A hypnotic and sedative. Its use has been largely superseded by other drugs. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Glutathimid
  • Glutethimid
  • Glutetimid
  • Glutetimide
  • Gluthetimide
Brand names
  • Alfimid
  • Doriden
  • Elrodorm
  • Gimid
  • Glimid
  • Noxiron
  • Noxyron
  • Ondasil
  • Rigenox
  • Sarodormin
Brand name mixtures Not Available
Categories
  • Hypnotics and Sedatives
CAS number 77-21-4
Weight Average: 217.2637
Monoisotopic: 217.110278729
Chemical Formula C13H15NO2
InChI Key InChIKey=JMBQKKAJIKAWKF-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)
Plain Text
IUPAC Name
3-ethyl-3-phenylpiperidine-2,6-dione
SMILES
CCC1(CCC(=O)NC1=O)C1=CC=CC=C1
Plain Text
Mass Spec show (9.4 KB)
Taxonomy
Kingdom Organic
Classes
  • Delta Lactams
  • Phenylpiperidines
Substructures
  • Carbonyl Compounds
  • Delta Lactams
  • Carboxylic Acids and Derivatives
  • Amino Ketones
  • Benzene and Derivatives
  • Phenylpiperidines
  • Piperidines
  • Phenethylamines
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxamides and Derivatives
Pharmacology
Indication For the treatment of insomnia.
Pharmacodynamics Glutethimide 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 action Glutethimide 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.
Absorption Variable
Volume of distribution Not Available
Protein binding Not Available
Metabolism

Hepatic. Glutethimide is almost completely metabolized.
Route of elimination glutethimide 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 life 10-12 hours
Clearance Not Available
Toxicity In 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
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Sanofi aventis us llc
  • Halsey drug co inc
  • Lannett co inc
  • Sandoz inc
  • Ucb inc
  • Vitarine pharmaceuticals inc
  • Watson laboratories inc
Packagers Not Available
Dosage forms Not Available
Prices Not Available
Patents Not Available
Properties
State solid
Melting point 84 oC
Experimental Properties
Property Value Source
water solubility 0.999 mg/mL at 30 oC [YALKOWSKY,SH & DANNENFELSER,RM (1992)] PhysProp
logP 1.90 [HANSCH,C ET AL. (1995)] PhysProp
logS -2.34 [ADME Research, USCD] PhysProp
pKa 9.2 Various sources
Predicted Properties
Property Value Source
water solubility 3.27e-01 g/l ALOGPS
logP 1.89 ALOGPS
logP 2.13 ChemAxon Molconvert
logS -2.82 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 2 ChemAxon Molconvert
hydrogen donor count 1 ChemAxon Molconvert
polar surface area 46.17 ChemAxon Molconvert
rotatable bond count 2 ChemAxon Molconvert
refractivity 60.65 ChemAxon Molconvert
polarizability 23.15 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00532 Link_out
KEGG Compound C07489 Link_out
PubChem Compound 3487 Link_out
PubChem Substance 46506283 Link_out
ChemSpider 3367 Link_out
Therapeutic Targets Database DAP001305 Link_out
PharmGKB PA449781 Link_out
Drug Product Database 0 Link_out
Wikipedia http://en.wikipedia.org/wiki/Glutethimide Link_out
ATC Codes
  • N05CE01
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions
  • Avoid alcohol.
  • Take without regard to meals.
Targets

1. Gamma-aminobutyric-acid receptor subunit alpha-1

Pharmacological action: yes
Actions: agonist

GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel

Organism class: human
UniProt ID: P14867 Link_out
Gene: GABRA1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Enzymes

1. Cholesterol side-chain cleavage enzyme, mitochondrial

Actions: inhibitor

Catalyzes the side-chain cleavage reaction of cholesterol to pregnenolone

UniProt ID: P05108 Link_out
Gene: CYP11A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: inducer

Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Comments
Drug created on July 26, 2007 13:33 / Updated on December 29, 2010 09:44

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.