Glutethimide
Encyclopedia
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.
, hallucinosis, convulsions and fever
.
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.
. 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, after it was discovered that misuse combined with codeine
increased the effect of the codeine and deaths had resulted from the combination.
), 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.
Hypnosis
Hypnosis is "a trance state characterized by extreme suggestibility, relaxation and heightened imagination."It is a mental state or imaginative role-enactment . It is usually induced by a procedure known as a hypnotic induction, which is commonly composed of a long series of preliminary...
sedative
Sedative
A sedative or tranquilizer is a substance that induces sedation by reducing irritability or excitement....
that was introduced in 1954 as a safe alternative to barbiturates to treat insomnia
Insomnia
Insomnia is most often defined by an individual's report of sleeping difficulties. While the term is sometimes used in sleep literature to describe a disorder demonstrated by polysomnographic evidence of disturbed sleep, insomnia is often defined as a positive response to either of two questions:...
. Before long, however, it had become clear that glutethimide was just as likely to cause addiction and caused similarly severe withdrawal
Withdrawal
Withdrawal can refer to any sort of separation, but is most commonly used to describe the group of symptoms that occurs upon the abrupt discontinuation/separation or a decrease in dosage of the intake of medications, recreational drugs, and alcohol...
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 deliriumDelirium
Delirium or acute confusional state is a common and severe neuropsychiatric syndrome with core features of acute onset and fluctuating course, attentional deficits and generalized severe disorganization of behavior...
, hallucinosis, convulsions and fever
Fever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
.
Recreational use
Glutethimide is a CYP2D6CYP2D6
Cytochrome P450 2D6 , a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. Also, many substances are bioactivated by CYP2D6 to form their active compounds...
enzyme inducer. When taken with codeine
Codeine
Codeine or 3-methylmorphine is an opiate used for its analgesic, antitussive, and antidiarrheal properties...
, it enables the body to convert higher amounts of the codeine (higher than the average 5 - 10%) to morphine
Morphine
Morphine is a potent opiate analgesic medication and is considered to be the prototypical opioid. It was first isolated in 1804 by Friedrich Sertürner, first distributed by same in 1817, and first commercially sold by Merck in 1827, which at the time was a single small chemists' shop. It was more...
. The general sedative effect also adds to the effect of the combination.
Legal status
Glutethimide is a Schedule II drug under the Convention on Psychotropic SubstancesConvention on Psychotropic Substances
The Convention on Psychotropic Substances of 1971 is a United Nations treaty designed to control psychoactive drugs such as amphetamines, barbiturates, benzodiazepines, and psychedelics signed at Vienna on February 21, 1971...
. It was originally a Schedule III drug in the United States under the Controlled Substances Act
Controlled Substances Act
The Controlled Substances Act was enacted into law by the Congress of the United States as Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970. The CSA is the federal U.S. drug policy under which the manufacture, importation, possession, use and distribution of certain...
, but in 1991 it was upgraded to Schedule II, after it was discovered that misuse combined with codeine
Codeine
Codeine or 3-methylmorphine is an opiate used for its analgesic, antitussive, and antidiarrheal properties...
increased the effect of the codeine and deaths had resulted from the combination.
Chemistry
Glutethimide (2-ethyl-2-phenylgutarimide) is synthesized by addition of 2-phenylbutyronitrile to the methylacrylate (Michael reactionMichael reaction
The Michael reaction or Michael addition is the nucleophilic addition of a carbanion or another nucleophile to an alpha, beta unsaturated carbonyl compound. It belongs to the larger class of conjugate additions. This is one of the most useful methods for the mild formation of C-C bonds...
), and the subsequent alkaline hydrolysis of the nitrile
Nitrile
A nitrile is any organic compound that has a -C≡N functional group. The prefix cyano- is used interchangeably with the term nitrile in industrial literature. Nitriles are found in many useful compounds, one example being super glue .Inorganic compounds containing the -C≡N group are not called...
group in the obtained compound into an amide
Amide
In chemistry, an amide is an organic compound that contains the functional group consisting of a carbonyl group linked to a nitrogen atom . The term refers both to a class of compounds and a functional group within those compounds. The term amide also refers to deprotonated form of ammonia or an...
group, and the subsequent acidic cyclization of the product into the desired glutethimide.