Identification

Name
Ethinamate
Accession Number
DB01031  (APRD00959)
Type
Small Molecule
Groups
Approved, Illicit, Withdrawn
Description

Ethinamate is a short-acting sedative-hypnotic medication used to treat insomnia. Regular use leads to tolerance, and it is usually not effective for more than 7 days. Structurally, it does not resemble the barbituates, but it shares many effects with this class of drugs; the depressant effects of ethinamate are, however, generally milder than those of most barbiturates.

Structure
Thumb
Synonyms
  • 1-Ethynylcyclohexanol carbamate
  • Aethinyl-cyclohexyl-carbamat
  • Ethinamate
  • Ethinamatum
  • Etinamato
External IDs
USAF EL-42
International/Other Brands
Valamin (Schering) / Valmid (Dista)
Categories
UNII
IAN371PP48
CAS number
126-52-3
Weight
Average: 167.205
Monoisotopic: 167.094628665
Chemical Formula
C9H13NO2
InChI Key
GXRZIMHKGDIBEW-UHFFFAOYSA-N
InChI
InChI=1S/C9H13NO2/c1-2-9(12-8(10)11)6-4-3-5-7-9/h1H,3-7H2,(H2,10,11)
IUPAC Name
1-ethynylcyclohexyl carbamate
SMILES
NC(=O)OC1(CCCCC1)C#C

Pharmacology

Indication

Used for the short-term treatment of insomnia, however, it generally has been replaced by other sedative-hypnotic agents.

Pharmacodynamics

Ethinamate is used to treat insomnia (trouble in sleeping). However, it has generally been replaced by other medicines for the treatment of insomnia. If ethinamate is used regularly (for example, every day) to help produce sleep, it is usually not effective for more than 7 days. Structurally, it does not resemble the barbiturates, but it shares many effects with this class of drugs; the depressant effects of ethinamate are, however, generally milder than those of most barbiturates. Continued and inappropriate use of ethinamate can lead to tolerance and physical dependence, with withdrawal symptoms very similar to those of the barbiturates.

Mechanism of action

The mechanism of action is not known. However, studies have shown that ethinamate inhibits carbonic anhydrases I and II (J Biol Chem. 1992 Dec 15;267(35):25044-50). This inhibition by ethinamate is not sufficiently strong, however, to implicate carbonic anhydrases I and II in the mechanism of action.

TargetActionsOrganism
ACarbonic anhydrase 1
inhibitor
Human
ACarbonic anhydrase 2
inhibitor
Human
Absorption

Rapidly absorbed following oral administration.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Hepatic.

Route of elimination
Not Available
Half life

2.5 hours

Clearance
Not Available
Toxicity

Symptoms of overdose include shortness of breath or slow or troubled breathing, slow heartbeat, severe weakness, chronic confusion, slurred speech, and staggering.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

Synthesis Reference

Junkmann, K. and Pfeiffer, H.; US. Patent 2,816,910; December 17, 1957; assigned to Schering AG, Germany.

General References
Not Available
External Links
Human Metabolome Database
HMDB0015165
KEGG Drug
D00703
KEGG Compound
C07832
PubChem Compound
3284
PubChem Substance
46507468
ChemSpider
3169
ChEBI
4884
ChEMBL
CHEMBL1576
Therapeutic Targets Database
DAP000606
PharmGKB
PA164745394
Wikipedia
Ethinamate

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)94-96Junkmann, K. and Pfeiffer, H.; US. Patent 2,816,910; December 17, 1957; assigned to Schering AG, Germany.
boiling point (°C)120 °C at 3.00E+00 mm HgPhysProp
water solubility2500 mg/L (at 25 °C)MERCK INDEX (1996)
logP1.2Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.106 mg/mLALOGPS
logP1.09ALOGPS
logP1.54ChemAxon
logS-3.2ALOGPS
pKa (Strongest Acidic)15.37ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area52.32 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity44.57 m3·mol-1ChemAxon
Polarizability17.73 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9809
Blood Brain Barrier+0.9923
Caco-2 permeable+0.5
P-glycoprotein substrateNon-substrate0.8609
P-glycoprotein inhibitor INon-inhibitor0.9198
P-glycoprotein inhibitor IINon-inhibitor0.972
Renal organic cation transporterNon-inhibitor0.8683
CYP450 2C9 substrateNon-substrate0.8427
CYP450 2D6 substrateNon-substrate0.7642
CYP450 3A4 substrateNon-substrate0.5213
CYP450 1A2 substrateNon-inhibitor0.7904
CYP450 2C9 inhibitorNon-inhibitor0.8493
CYP450 2D6 inhibitorNon-inhibitor0.9299
CYP450 2C19 inhibitorNon-inhibitor0.8006
CYP450 3A4 inhibitorNon-inhibitor0.852
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8627
Ames testNon AMES toxic0.669
CarcinogenicityNon-carcinogens0.8886
BiodegradationNot ready biodegradable0.9584
Rat acute toxicity2.6719 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9551
hERG inhibition (predictor II)Non-inhibitor0.9467
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - EI-BGC-MSsplash10-054o-9000000000-115ca538c5db7623cd36
GC-MS Spectrum - CI-BGC-MSsplash10-004i-0900000000-3530aac44af3672b4ea8
Mass Spectrum (Electron Ionization)MSsplash10-0arv-9100000000-713c62aa52e71fc3560a
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as ynones. These are organic compounds containing the ynone functional group, an alpha,beta unsaturated ketone group with the general structure RC#C-C(=O)R' (R' not H).
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Carbonyl compounds
Direct Parent
Ynones
Alternative Parents
Carbamate esters / Organic carbonic acids and derivatives / Acetylides / Organopnictogen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives
Substituents
Ynone / Carbamic acid ester / Carbonic acid derivative / Acetylide / Organic nitrogen compound / Organopnictogen compound / Organic oxide / Hydrocarbon derivative / Organonitrogen compound / Aliphatic homomonocyclic compound
Molecular Framework
Aliphatic homomonocyclic compounds
External Descriptors
terminal acetylenic compound, carbamate ester (CHEBI:4884)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Zinc ion binding
Specific Function
Reversible hydration of carbon dioxide. Can hydrates cyanamide to urea.
Gene Name
CA1
Uniprot ID
P00915
Uniprot Name
Carbonic anhydrase 1
Molecular Weight
28870.0 Da
References
  1. Parr JS, Khalifah RG: Inhibition of carbonic anhydrases I and II by N-unsubstituted carbamate esters. J Biol Chem. 1992 Dec 15;267(35):25044-50. [PubMed:1460006]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Zinc ion binding
Specific Function
Essential for bone resorption and osteoclast differentiation (By similarity). Reversible hydration of carbon dioxide. Can hydrate cyanamide to urea. Involved in the regulation of fluid secretion in...
Gene Name
CA2
Uniprot ID
P00918
Uniprot Name
Carbonic anhydrase 2
Molecular Weight
29245.895 Da
References
  1. Parr JS, Khalifah RG: Inhibition of carbonic anhydrases I and II by N-unsubstituted carbamate esters. J Biol Chem. 1992 Dec 15;267(35):25044-50. [PubMed:1460006]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Drug created on June 13, 2005 07:24 / Updated on November 02, 2018 04:54