Ethinamate

Ethinamate
Clinical data
Trade namesValmid, Valamin
AHFS/Drugs.comMicromedex Detailed Consumer Information
Pregnancy
category
  • C
Routes of
administration		Oral
ATC code
  • none
Legal status
Legal status
Pharmacokinetic data
Elimination half-life2.5 hours
Identifiers
  • (1-ethynylcyclohexyl)carbamate
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.004.355 Edit this at Wikidata
Chemical and physical data
FormulaC9H13NO2
Molar mass167.208 g·mol−1
3D model (JSmol)
  • O=C(OC1(C#C)CCCCC1)N
  • InChI=1S/C9H13NO2/c1-2-9(12-8(10)11)6-4-3-5-7-9/h1H,3-7H2,(H2,10,11) checkY
  • Key:GXRZIMHKGDIBEW-UHFFFAOYSA-N checkY
  (verify)

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

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 commonly prescribed in Germany, the United States, Australia, Canada, the Netherlands, and much[dubious – discuss][clarification needed] of Europe. Ethinamate is not known to be available in any country. Despite being available in the U.S. until 1982, ethinamate largely fell out of favor by the 1960s, as contemporary novel sedatives were viewed as safer alternatives, including methaqualone, ethchlorvynol, glutethimide, methyprylon, meprobamate, and by the 1960s, chlordiazepoxide and diazepam.

Recognition

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

The compound is synthesized by reacting acetylene with cyclohexanone to form 1-ethynylcyclohexanol. This intermediate is then 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.

Ethinamate, whose molecular structure is known as 1-ethynylcyclohexane carbamate is an odorless, white crystalline powder. It is typically formulated as 500 mg tablets for oral administration, with an adult dose of one tablet at bedtime; two tablets may be taken if necessary. Children are more prone to paradoxical effects and the drug is not indicated for individuals under 18.[citation needed]The compound is synthesized by reacting acetylene with cyclohexanone to form 1-ethynylcyclohexanol. This intermediate is then 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. 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.

References

  1. ↑ Anvisa (31 March 2023). "RDC Nº 784 – Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 – Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 4 April 2023). Archived from the original on 3 August 2023. Retrieved 16 August 2023.
  2. 1 2 "Victoria Museum of Pharmacology". Valamin at the Victoria Museum of Pharmacy. Retrieved 18 January 2026.
  3. 1 2 "Ethinamate (Valmid, Valamin): Overview". PubChem. Retrieved 2 May 2025.
  4. 1 2 Lowry WT, Garriot JC (1979). "Ethinamate". Forensic Toxicology: Controlled Substances and Dangerous Drugs. Boston, MA: Springer US. p. 215. ISBN 978-1-4684-3444-6.
  5. ↑ Cole J, Thompson C (2 August 2017). "The Death of Elvis". Memphis Magazine. Memphis Magazine. Retrieved 4 September 2025.
  6. 1 2 US 2816910, Pfeiffer H, Junkman K, "Esters of carbamic acid and a method of making same", issued 17 December 1957, assigned to Schering AG
  7. 1 2 DE 1021843, Emde H, Grimme W, "Verfahren zur Herstellung des Allophanats des 1-AEthinylcyclohexanols-(1)", issued 2 January 1958, assigned to Rheinpreussen AG