GLUTETHIMIDE

US Previously Marketed

Details

Stereochemistry	RACEMIC
Molecular Formula	C13H15NO2
Molecular Weight	217.2637
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCC1(CCC(=O)NC1=O)C2=CC=CC=C2

InChI

InChIKey=JMBQKKAJIKAWKF-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Description
Sources: https://www.drugs.com/mmx/glutethimide.html
Curator's Comment: description was created based on several sources, including https://www.drugbank.ca/drugs/DB01437 | https://www.ncbi.nlm.nih.gov/pubmed/2549762 | https://www.ncbi.nlm.nih.gov/pubmed/14193389

Glutethimide is a GABA agonist that was introduced by Ciba 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. Glutethimide was discontinued in the US by manufacturers in 1993. Current production levels in the United States point to it only being used in small-scale research.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
GABA-A receptor; anion channel 202 Target ID: CHEMBL2093872 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2845220	Positive Allosteric Modulator 179

Conditions

Condition	Modality	Targets	Highest Phase	Product
Insomnia 108 Sources: https://www.drugs.com/mmx/glutethimide.html	Primary		Approved 8429	GLUTETHIMIDE Approved Use Unknown Launch Date 2.15308796E11

C_max

Value	Dose	Analyte	Population
4.34 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/5568259/	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:	GLUTETHIMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
5 μg/mL OTHER https://www.pharmacompass.com/chemistry-chemical-name/glutethimide	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:	GLUTETHIMIDE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
6.5 μg/mL OTHER https://www.pharmacompass.com/chemistry-chemical-name/glutethimide	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:	GLUTETHIMIDE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
33.51 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/902458/	500 mg 3 times / day multiple, oral dose: 500 mg route of administration: Oral experiment type: MULTIPLE co-administered:		GLUTETHIMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
11.6 h OTHER https://www.pharmacompass.com/chemistry-chemical-name/glutethimide			GLUTETHIMIDE serum	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
45.8% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/5568259/	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:		GLUTETHIMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED

Doses

Dose	Population	Adverse events
4 g multiple, oral (max) Overdose Dose: 4 g Route: oral Route: multiple Dose: 4 g Sources: https://pubmed.ncbi.nlm.nih.gov/5709841 Page: p.561	unhealthy, 42 n = 1 Health Status: unhealthy Condition: alcohol addiction Age Group: 42 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/5709841 Page: p.561	Disc. AE: Cerebellar ataxia... AEs leading to discontinuation/dose reduction: Cerebellar ataxia (severe) Sources: https://pubmed.ncbi.nlm.nih.gov/5709841 Page: p.561
10 g single, oral (min) Overdose Dose: 10 g Route: oral Route: single Dose: 10 g Sources: https://pubmed.ncbi.nlm.nih.gov/512618	unknown Health Status: unknown Sources: https://pubmed.ncbi.nlm.nih.gov/512618	Disc. AE: Coma... AEs leading to discontinuation/dose reduction: Coma (grade 4-5) Sources: https://pubmed.ncbi.nlm.nih.gov/512618
15000 mg single, oral Overdose Dose: 15000 mg Route: oral Route: single Dose: 15000 mg Sources: https://pubmed.ncbi.nlm.nih.gov/18818183 Page: p.72, 74	healthy n = 1 Health Status: healthy Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/18818183 Page: p.72, 74	Disc. AE: Unconsciousness, Uremia... AEs leading to discontinuation/dose reduction: Unconsciousness (grade 4) Uremia (severe) Multiorgan failure (severe) Multiple congenital abnormalities (severe) Sources: https://pubmed.ncbi.nlm.nih.gov/18818183 Page: p.72, 74

AEs

AE	Significance	Dose	Population
Cerebellar ataxia	severe Disc. AE	4 g multiple, oral (max) Overdose Dose: 4 g Route: oral Route: multiple Dose: 4 g Sources: https://pubmed.ncbi.nlm.nih.gov/5709841 Page: p.561	unhealthy, 42 n = 1 Health Status: unhealthy Condition: alcohol addiction Age Group: 42 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/5709841 Page: p.561
Coma	grade 4-5 Disc. AE	10 g single, oral (min) Overdose Dose: 10 g Route: oral Route: single Dose: 10 g Sources: https://pubmed.ncbi.nlm.nih.gov/512618	unknown Health Status: unknown Sources: https://pubmed.ncbi.nlm.nih.gov/512618
Unconsciousness	grade 4 Disc. AE	15000 mg single, oral Overdose Dose: 15000 mg Route: oral Route: single Dose: 15000 mg Sources: https://pubmed.ncbi.nlm.nih.gov/18818183 Page: p.72, 74	healthy n = 1 Health Status: healthy Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/18818183 Page: p.72, 74
Multiorgan failure	severe Disc. AE	15000 mg single, oral Overdose Dose: 15000 mg Route: oral Route: single Dose: 15000 mg Sources: https://pubmed.ncbi.nlm.nih.gov/18818183 Page: p.72, 74	healthy n = 1 Health Status: healthy Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/18818183 Page: p.72, 74
Multiple congenital abnormalities	severe Disc. AE	15000 mg single, oral Overdose Dose: 15000 mg Route: oral Route: single Dose: 15000 mg Sources: https://pubmed.ncbi.nlm.nih.gov/18818183 Page: p.72, 74	healthy n = 1 Health Status: healthy Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/18818183 Page: p.72, 74
Uremia	severe Disc. AE	15000 mg single, oral Overdose Dose: 15000 mg Route: oral Route: single Dose: 15000 mg Sources: https://pubmed.ncbi.nlm.nih.gov/18818183 Page: p.72, 74	healthy n = 1 Health Status: healthy Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/18818183 Page: p.72, 74

Sourcing

Vendor/Aggregator	ID	URL
ChemIDplus	60490746	https://chem.nlm.nih.gov/chemidplus/id/0060490746
PubChem	133065417	https://pubchem.ncbi.nlm.nih.gov/compound/133065417
Wikidata	Q27270160

PubMed

Title	Date	PubMed
Neurological effects of glutethimide.	1968 Dec	5709841
[Hypocalcemic seizures after misuse of glutethimide (Doriden)].	1976 May 10	1273917
Anti-convulsant effect of phthalazino-2,3b-phthalazine-5(14H),12(7h)-dione (L-5418). I. Behavioral effect.	1978 Feb	565846
Catatonia associated with glutethimide withdrawal.	1983 Jan	6822484
Lack of correlation between plasma 4-hydroxyglutethimide and severity of coma in acute glutethimide poisoning. A case report and brief review of the literature.	1987 Jul-Aug	3626855
Glutethimide intoxication and withdrawal.	1988 Apr	3348460
Mechanism of iron potentiation of hepatic uroporphyria: studies in cultured chick embryo liver cells.	1989 Sep	2759551
Differential expression of c-fos and c-myc protooncogenes by estrogens, xenobiotics and other growth-stimulatory agents in primary rat hepatocytes.	2003 Mar	12632255

Patents

Sample Use Guides

In Vivo Use Guide

Usual adult dose: 500 mg at bedtime; dose may be repeated if necessary, but not less than four hours before patient arises

Route of Administration: Oral

In Vitro Use Guide

Chick embryo liver cells (CELCs) and chicken hepatoma cell line (LMH) were used to evaluate 5-Aminolevulinic acid synthase (ALA synthase) activity. CELCs and LMH cells were treated with Glutethimide (50mkM) or Glutethimide (50mkM)+ 4,6-dioxoheptanoic acid (0-500mkM)) and maintained for 18 h, after which cells were harvested, sonicates prepared and used to measure ALA synthase activity. The combination of glutethimide and DHA synergistically increased ALA synthase activity in both CELCs and LMH cells

Name

Type

Language

GLUTETHIMIDE

Official Name

English

GLUTETHIMIDE [MART.]

Common Name

English

GLUTETHIMIDE [VANDF]

Common Name

English

GLUTETHIMIDE [MI]

Common Name

English

2-Ethyl-2-phenylglutarimide

Systematic Name

English

DORIDEN

Brand Name

English

2,6-PIPERIDINEDIONE, 3-ETHYL-3-PHENYL-

Systematic Name

English

ELRODORM

Common Name

English

NOXYRON

Common Name

English

glutethimide [INN]

Common Name

English

GLUTETHIMIDE [JAN]

Common Name

English

NSC-95239

Code

English

GLUTETHIMIDE [ORANGE BOOK]

Common Name

English

RIGENOX

Common Name

English

GLUTETHIMIDE [HSDB]

Common Name

English

SARODORMIN

Common Name

English

Glutethimide [WHO-DD]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29756