Ethinamate

Ethinamate

Clinical data
Trade names	Valmid, Valamin
AHFS/Drugs.com	Micromedex Detailed Consumer Information
Pregnancy category	C
Routes of administration	Oral
ATC code	none
Legal status
Legal status	BR: Class B1 (Psychoactive drugs) [1] CA: Schedule IV DE: Anlage II (Authorized trade only, not prescriptible) UK: Class C US: Schedule IV In general: ℞ (Prescription only)
Pharmacokinetic data
Elimination half-life	2.5 hours
Identifiers
IUPAC name (1-ethynylcyclohexyl)carbamate
CAS Number	126-52-3  Y
PubChem CID	3284
IUPHAR/BPS	7325
DrugBank	DB01031  Y
ChemSpider	3169  Y
UNII	IAN371PP48
KEGG	D00703  Y
ChEBI	CHEBI:4884  Y
ChEMBL	ChEMBL1576  Y
CompTox Dashboard (EPA)	DTXSID7023013
ECHA InfoCard	100.004.355
Chemical and physical data
Formula	C9H13NO2
Molar mass	167.208 g·mol−1
3D model (JSmol)	Interactive image
SMILES O=C(OC1(C#C)CCCCC1)N
InChI InChI=1S/C9H13NO2/c1-2-9(12-8(10)11)6-4-3-5-7-9/h1H,3-7H2,(H2,10,11) Y Key:GXRZIMHKGDIBEW-UHFFFAOYSA-N Y
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Ethinamate, marketed as Valmid in the United States and Valamin in Australia, ^[2] 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. ^[3]

Availability

Ethinamate was introduced by German drug company Schering AG in 1957, marketed as as a sleeping pill with "barbiturate-like" effects and 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 of Europe. ^{[2] [4]} 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 tranquilizers with less tolerance and longer duration of action were viewed as more effective – including methaqualone, ethchlorvynol, glutethimide, methyprylon, meprobamate, and the benzodiazepines chlordiazepoxide and diazepam In the United States, ethinamate is now primarily remembered in connection with the toxicology reports on the death of Elvis Presley: it was listed among multiple sedatives detected in his system, and some forensic experts, including Cyril Wecht, later emphasized that polypharmacy was an important factor in the case. ^[5]

Toxicity and overdose

Ethinamate has a wider therapeutic index and safety profile compared to barbiturates, with drug overdose of the former rarely causing fatality by respiratory depression (as is more likely in barbiturate overdose). Reported cases illustrate that doses as high as 2,800 mg induce temporary loss of consciousness or comatose state, though recovery is possible and likely with supportive care. Activated charcoal may reduce absorption if administered early (25–100 g for adults; 25–50 g in children under 12; 1 g/kg in infants), and hemodialysis can be considered in severe cases.^{[ citation needed ]}

Adverse effects and safety in pregnancy

Ethinamate's primary effects result from CNS depression, manifesting as a slow heart rate, shallow breathing, and low blood pressure. Minor side effects at therapeutic doses include nausea, vomiting, gastrointestinal upset, and skin rash. Rare hypersensitivity reactions may involve thrombocytopenia purpura, fever, and rashes. Children are more likely than adults to experience paradoxical effects, so the drug was not indicated for individuals under 18.^{[ citation needed ]}

Hypersensitivity reactions may involve thrombocytopenia purpura, fever, and various skin rashes. ^[4]

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. ^{[6] [7]}

Ethinamate, whose molecular structure is known as 1-ethynylcyclohexanyneone 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. ^{[6] [7]}

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. ^[3]

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. "Victoria Museum of Pharmacology". Valamin at the Victoria Museum of Pharmacy. Retrieved 18 January 2026.
3. "Ethinamate (Valmid, Valamin): Overview". PubChem. Retrieved 2 May 2025.
4. 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. 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. DE 1021843,Emde H, Grimme W,"Verfahren zur Herstellung des Allophanats des 1-AEthinylcyclohexanols-(1)",issued 2 January 1958, assigned to Rheinpreussen AG