Glutethimide is a hypnoticsedative 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 similar withdrawal symptoms. Doriden was the brand-name version. Current production levels in the United States point to it being used only in small scale research. Manufacturing of the drug was discontinued in the US in 1993 and discontinued in several eastern European countries in 2006.
Glutethimide is a CYP2D6enzyme inducer. When taken with codeine, it enables the body to convert higher amounts of the codeine to morphine. The general sedative effect of the glutethimide also adds to the effect of the combination. It produces an intense, long lasting euphoria similar to IV heroin use. Quite a few deaths have occurred from abuse of this 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 agonistsubstitution therapy, e.g. as a Substitutionmittel that may be a useful alternative to methadone. The demand for this combination in Philadelphia, Pittsburgh, Newark, NYC, Boston, Baltimore, and surrounding areas of other states and perhaps elsewhere, has led to small-scale clandestine synthesis of glutethimide since 1984, a process that is, like methaqualone synthesis, somewhat difficult and fraught with potential bad outcomes when amateur chemists manufacture the drugs 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. Production of glutethimide was discontinued in the US in 1993 and in several eastern European countries, most notably Hungary, in 2006. Analysis of confiscated glutethimide seems to invariably show the drug or the results of attempted synthesis, whereas purported methaqualone is in a significant majority of cases found to be inert, or contain diphenhydramine or benzodiazepines.
Glutethimide is synthesized by addition of 2-phenylbutanenitrile to the methylacrylate, 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. The isomer has a faster onset and more potent anticonvulsant activity in animal models than the isomer.
