Glutethimide

Jump to: navigation, search
Glutethimide
Glutethimide.png
Glutethimide ball-and-stick.png
Clinical data
Pregnancy
category
  • C: (United States)
Routes of
administration
oral
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • US: Schedule II

  • Schedule III international
Pharmacokinetic data
BioavailabilityVariable
MetabolismHepatic
Elimination half-life10-12 hours
ExcretionRenal:2% Fecal:2%
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
E number{{#property:P628}}
ECHA InfoCard{{#property:P2566}}Lua error in Module:EditAtWikidata at line 36: attempt to index field 'wikibase' (a nil value).
Chemical and physical data
FormulaC13H15NO2
Molar mass217.264 g/mol
3D model (JSmol)
  (verify)

WikiDoc Resources for Glutethimide

Articles

Most recent articles on Glutethimide

Most cited articles on Glutethimide

Review articles on Glutethimide

Articles on Glutethimide in N Eng J Med, Lancet, BMJ

Media

Powerpoint slides on Glutethimide

Images of Glutethimide

Photos of Glutethimide

Podcasts & MP3s on Glutethimide

Videos on Glutethimide

Evidence Based Medicine

Cochrane Collaboration on Glutethimide

Bandolier on Glutethimide

TRIP on Glutethimide

Clinical Trials

Ongoing Trials on Glutethimide at Clinical Trials.gov

Trial results on Glutethimide

Clinical Trials on Glutethimide at Google

Guidelines / Policies / Govt

US National Guidelines Clearinghouse on Glutethimide

NICE Guidance on Glutethimide

NHS PRODIGY Guidance

FDA on Glutethimide

CDC on Glutethimide

Books

Books on Glutethimide

News

Glutethimide in the news

Be alerted to news on Glutethimide

News trends on Glutethimide

Commentary

Blogs on Glutethimide

Definitions

Definitions of Glutethimide

Patient Resources / Community

Patient resources on Glutethimide

Discussion groups on Glutethimide

Patient Handouts on Glutethimide

Directions to Hospitals Treating Glutethimide

Risk calculators and risk factors for Glutethimide

Healthcare Provider Resources

Symptoms of Glutethimide

Causes & Risk Factors for Glutethimide

Diagnostic studies for Glutethimide

Treatment of Glutethimide

Continuing Medical Education (CME)

CME Programs on Glutethimide

International

Glutethimide en Espanol

Glutethimide en Francais

Business

Glutethimide in the Marketplace

Patents on Glutethimide

Experimental / Informatics

List of terms related to Glutethimide

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Glutethimide is a hypnotic sedative that was introduced by Ciba[1] 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 was the brand-name version of the drug; it was also available under the brand names Elrodorm, Noxyron, Glimid and others. Both the generic and brand-name forms are very rarely prescribed today. Current production levels in the United States (the annual quota for manufacturing imposed by the DEA has been three grams, enough for six Doriden tablets, for a number of years) point to it only being used in small scale research.

Long term use

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.[2]

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. The effect was also used clinically, including some research in the 1970s in various countries of using it under carefully monitored circumstances as a form of oral opioid agonist substitution therapy, e.g. as a Substitutionmittel that may be a useful alternative to methadone[3][4] The combination was known as Dors & Fours, a Six Pack, Loads, etc. as two Doriden tablets and four Tylenol (or Emprin, Emprazil or other drugs) With Codeine No. 4, or plain 60 mg codeine tablets were sold as a set. The demand for this combination, in western Pennsylvania and surrounding areas of other states and perhaps elsewhere, has led to small-scale clandestine synthesis of glutethimide since 1984,[5] a process that is, like methaqualone synthesis, somewhat difficult and fraught with potential bad outcomes when less-than-gifted chemists are doing the deed with industrial-grade precursors without adequate quality control. The fact that the simpler clandestine synthesis of other extinct pharmaceutical depressants like ethchlorvynol, methyprylon, or the oldest barbiturates is not reported would seem to point to a high level of motivation surrounding a unique drug, again much like methaqualone. Analysis of confiscated glutethimide seems to invariably show the drug or the results of attempted synthesis, whereas purported methaqualone is in a significant minority of cases found to be inert, or contain diphenhydramine or benzodiazepines [6]

The enzyme induction is apparently several times stronger than that induced by promethazine (Phenergan, Atosil), a phenothiazine antihistamine used clinically as an opioid potentiator (Phenergan VC With Codeine, Mepergan (pethidine + promethazine), mixing the antihistamine with alphaprodine and other such drugs in an IV)

Legal status

Glutethimide is a Schedule II drug under the Convention on Psychotropic Substances.[7] 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,[8] after it was discovered that misuse combined with codeine increased the effect of the codeine and deaths had resulted from the combination.[9][10] It has a DEA ACSCN of 2550 and a 2013 production quota of 3 g.

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.[11] The (R) isomer has a faster onset and more potent anticonvulsant activity in animal models than the (S) isomer.[12]

See also

References

  1. US patent 2673205, Hoffmann, K.; Tagmann, E., "3-Disubstituted Dioxopiperidines and the Manufacture thereof", issued 1954-03-23, assigned to Ciba 
  2. PMID 7562864 (PMID 7562864)
    Citation will be completed automatically in a few minutes. Jump the queue or expand by hand
  3. PMID 12899973 (PMID 12899973)
    Citation will be completed automatically in a few minutes. Jump the queue or expand by hand
  4. PMID 7135952 (PMID 7135952)
    Citation will be completed automatically in a few minutes. Jump the queue or expand by hand
  5. Gahlinger, 2001, pp 203
  6. Gahlinger, 2001 Ch "Methaqualone & Glutethimide"
  7. "List of psychotropic substances under international control" (pdf). INCB.
  8. "Code of Federal Regulations Section 1308.12 Schedule II". DEA.
  9. PMID 3998703 (PMID 3998703)
    Citation will be completed automatically in a few minutes. Jump the queue or expand by hand
  10. PMID 6695899 (PMID 6695899)
    Citation will be completed automatically in a few minutes. Jump the queue or expand by hand
  11. Template:Cite doi
    DE patent 950193, Hoffmann, K. & Tagmann, E., "Verfahren zur Herstellung neuer Dioxopiperidine" 
    US patent 2673205, Hoffmann, K. & Tagmann, E., "3-disubstituted dioxopiperidines and the manufacture thereof" 
    Salmon-Legagneur, F.; Neveu, C. (1952). Compt. Rend. 234: 1060. Missing or empty |title= (help)
    Salmon-Legagneur, F.; Neveu, C. (1953). Bull. Soc. Chim. France. 70. Missing or empty |title= (help)
  12. Annual Report in Medicinal Chemistry Volume 12 page 13

Linked-in.jpg