Glutethimide

Glutethimide

Systematic (IUPAC) name
3-ethyl-3-phenyl-piperidine-2,6-dione
Clinical data
Pregnancy cat.	C: (United States)
Legal status	Schedule II (US) Schedule III international
Routes	oral
Pharmacokinetic data
Bioavailability	Variable
Metabolism	Hepatic
Half-life	10-12 hours
Excretion	Renal:2% Fecal:2%
Identifiers
CAS number	77-21-4
ATC code	N05CE01
PubChem	CID 3487
DrugBank	DB01437
ChemSpider	3367
UNII	C8I4BVN78E
KEGG	D00532
ChEMBL	CHEMBL1102
Chemical data
Formula	C13H15NO2
Mol. mass	217.264 g/mol
SMILES	eMolecules & PubChem
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)  Key:JMBQKKAJIKAWKF-UHFFFAOYSA-N
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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. Doriden is the brand-name version of the drug; both the generic and brand-name forms are rarely prescribed today.

Long term use

In long term use rebound effects , which resembled those seen in withdrawal, have anecdotally been described in patients, who were still taking a stable dose of the drug. The symptoms included delirium, hallucinosis, convulsions and fever.^[1]

Recreational use

Glutethimide is a CYP2D6 enzyme inducer. 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 effect of the combination.^[2][3]

Legal status

Glutethimide is a Schedule II drug under the Convention on Psychotropic Substances.^[4] It was originally a Schedule III drug in the United States under the Controlled Substances Act, but in 1991 it was upgraded to Schedule II^[5], after it was discovered that misuse combined with codeine increased the effect of the codeine and deaths had resulted from the combination.^[6][7]

Chemistry

Glutethimide (2-ethyl-2-phenylgutarimide) is synthesized by addition of 2-phenylbutyronitrile to the methylacrylate (Michael reaction), and the subsequent alkaline hydrolysis of the nitrile group in the obtained compound into an amide group, and the subsequent acidic cyclization of the product into the desired glutethimide.^[8]

See also

• Aminoglutethimide
• Piperidione
• Methyprylone
• Pyrithyldione

References