Identification

Name
Glutethimide
Accession Number
DB01437
Type
Small Molecule
Groups
Approved, Illicit
Description

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 Its use has been largely superseded by other drugs.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

Structure
Thumb
Synonyms
  • 2-Ethyl-2-phenylglutarimide
  • Doriden
International/Other Brands
Doriden (U.S.V .) / Elrodorm / Glimid (Polfa Pabianice) / Glutethimid (Balkanpharma) / Noxyron
Categories
UNII
C8I4BVN78E
CAS number
77-21-4
Weight
Average: 217.2637
Monoisotopic: 217.110278729
Chemical Formula
C13H15NO2
InChI Key
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)
IUPAC Name
3-ethyl-3-phenylpiperidine-2,6-dione
SMILES
CCC1(CCC(=O)NC1=O)C1=CC=CC=C1

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.

TargetActionsOrganism
AGamma-aminobutyric acid receptor subunit alpha-1
agonist
Human
AGABA-A receptor (anion channel)
positive allosteric modulator
Human
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
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
7-NitroindazoleThe risk or severity of adverse effects can be increased when Glutethimide is combined with 7-Nitroindazole.
AcenocoumarolThe metabolism of Acenocoumarol can be increased when combined with Glutethimide.
AcepromazineThe risk or severity of adverse effects can be increased when Glutethimide is combined with Acepromazine.
AceprometazineThe risk or severity of adverse effects can be increased when Glutethimide is combined with Aceprometazine.
AcetazolamideThe risk or severity of adverse effects can be increased when Glutethimide is combined with Acetazolamide.
AdipiplonThe risk or severity of adverse effects can be increased when Glutethimide is combined with Adipiplon.
AgomelatineThe risk or severity of adverse effects can be increased when Glutethimide is combined with Agomelatine.
AlaproclateThe risk or severity of adverse effects can be increased when Glutethimide is combined with Alaproclate.
AlfaxaloneThe risk or severity of adverse effects can be increased when Glutethimide is combined with Alfaxalone.
AlfentanilThe risk or severity of adverse effects can be increased when Alfentanil is combined with Glutethimide.
Food Interactions
  • Avoid alcohol.
  • Take without regard to meals.

References

Synthesis Reference

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

General References
Not Available
External Links
Human Metabolome Database
HMDB0015505
KEGG Drug
D00532
KEGG Compound
C07489
PubChem Compound
3487
PubChem Substance
46506283
ChemSpider
3367
ChEBI
5439
ChEMBL
CHEMBL1102
Therapeutic Targets Database
DAP001305
PharmGKB
PA164749505
Wikipedia
Glutethimide
ATC Codes
N05CE01 — Glutethimide

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)78-81Hoffmann, 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 RuleNoChemAxon
MDDR-like RuleNoChemAxon
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 inhibitorNon-inhibitor0.9101
CYP450 2D6 inhibitorNon-inhibitor0.8664
CYP450 2C19 inhibitorNon-inhibitor0.8671
CYP450 3A4 inhibitorNon-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
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (9.43 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - CI-BGC-MSsplash10-014i-0090000000-df13dd29711d257fd7b0
GC-MS Spectrum - EI-BGC-MSsplash10-014r-4900000000-8d3add816c0b57475d49
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Piperidines
Sub Class
Phenylpiperidines
Direct Parent
Phenylpiperidines
Alternative Parents
Piperidinediones / Delta lactams / Benzene and substituted derivatives / N-unsubstituted carboxylic acid imides / Dicarboximides / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives
show 1 more
Substituents
Phenylpiperidine / Piperidinedione / Delta-lactam / Piperidinone / Monocyclic benzene moiety / Benzenoid / Carboxylic acid imide / Dicarboximide / Carboxylic acid imide, n-unsubstituted / Lactam
show 11 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
piperidines (CHEBI:5439)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Inhibitory extracellular ligand-gated ion channel activity
Specific Function
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine...
Gene Name
GABRA1
Uniprot ID
P14867
Uniprot Name
Gamma-aminobutyric acid receptor subunit alpha-1
Molecular Weight
51801.395 Da
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:6318143]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, nad(p)h as one donor, and incorporation of one atom of oxygen
Specific Function
Catalyzes the side-chain cleavage reaction of cholesterol to pregnenolone.
Gene Name
CYP11A1
Uniprot ID
P05108
Uniprot Name
Cholesterol side-chain cleavage enzyme, mitochondrial
Molecular Weight
60101.87 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Steroid hydroxylase activity
Specific Function
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...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Pearson MW, Roberts CJ: Drug induction of hepatic enzymes in the elderly. Age Ageing. 1984 Sep;13(5):313-6. [PubMed:6496244]
  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. doi: 10.1177/0748233708089014. [PubMed:18818183]

Drug created on July 26, 2007 13:33 / Updated on October 06, 2018 17:53