Ethinamate, marketed as Valmid in the United States and Valamin in Australia, is a central nervous system depressant of the carbamate drug class. It was formerly prescribed as a hypnotic for the short-term treatment of insomnia. The drug has a rapid onset of action, a short elimination half-life of around 2.5 hours, and a correspondingly brief duration of effect. Prolonged use leads to drug tolerance, drug dependence, and diminished efficacy after seven days of continuous use.

Availability and recognition

Ethinamate was introduced by German drug company Schering AG in 1957, marketed as a sleeping pill with a reduced risk of fatality in drug overdose compared to barbiturate overdose. Ethinamate was prescribed in Germany, the United States, Australia, Canada, and the Netherlands. though use peaked in the 1960s, and the trade name patent for Valmid expired in the U.S. in January 1982. Ethinamate was overdhadowed by broader-acting contemporary sedatives, including methaqualone, ethchlorvynol, glutethimide, methyprylon, meprobamate, chlordiazepoxide, and diazepam.

In the United States, ethinamate is now primarily associated with the death of Elvis Presley, as it was listed among multiple sedatives detected in toxicology reports, leading forensic expert Cyril Wecht to emphasized the important role of polypharmacy in the case.

Toxicity and overdose

Ethinamate debuted nearly at the same time as methyprylon and other "nonbarbiturate soporifics," including ethchlorvynol and glutethimide, were being developed and released continuously. Supratherapeutic dosing of 3,000 mg (nearly seven-fold a therapeutic dose) induced a temporary loss of consciousness or comatose state, but resulted in full recovery.

Activated charcoal may reduce absorption if administered early, and hemodialysis can be considered in severe cases.[citation needed][dubious– discuss]

Adverse effects and safety in pregnancy

Common side effects at therapeutic doses are gastrointestinal upset (nausea, vomiting, gastrointestinal upset, rare reactions indicative of hypersensitivity involve thrombocytopenia purpura, fever and various skin rashes[clarification needed]. The drug is classified as pregnancy Category C, and is not recommended during pregnancy or breastfeeding due to insufficient evidence regarding potential teratogenic effects. Animal studies suggest porphyrinogenic potential in vivo. [citation needed]

Chemistry and synthesis

Ethinamate's molecular structure is 1-ethynylcyclohexanol, which is synthesized by reacting acetylene with cyclohexanone, forming an intermediate which is converted into a carbamate through reaction with phosgene and ammonia. Small amounts of lithium or similar reagents may be used to facilitate the initial acetylene reaction, producing an odorless, white crystalline powder, individual formulations comprising 500 mg tablets for oral administration. Children are more prone to paradoxical effects and the drug is not indicated for individuals under 18. After ingestion, ethinamate is metabolized to the active compound 4-hydroxyethinamate, which is eliminated in urine with a half-life of approximately 2.5 hours.