U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C18H27NO5
Molecular Weight 337.4107
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PROPANIDID

SMILES

CCCOC(=O)CC1=CC(OC)=C(OCC(=O)N(CC)CC)C=C1

InChI

InChIKey=KEJXLQUPYHWCNM-UHFFFAOYSA-N
InChI=1S/C18H27NO5/c1-5-10-23-18(21)12-14-8-9-15(16(11-14)22-4)24-13-17(20)19(6-2)7-3/h8-9,11H,5-7,10,12-13H2,1-4H3

HIDE SMILES / InChI

Description

Propanidid (Epontol) is an analgetically potent and shortterm anesthetic, widely used in the 1960s. It was originally introduced by Bayer in 1963. Epontol, an injectable emulsion formulation of propanidid, provided by Bayer, was withdrawn from the market in Great Britain in 1983 because of concern over anaphylactoid reactions. Thus, in spite of the fact that propanidid provides shorter and more predictable recovery times than propofol, it has not been accepted widely as an injectable anesthetic. Even though Cremophor EL has been shown to cause anaphylactic reactions in humans in several cases (both when given intravenously and orally), it is still debated whether or not propanidid itself may have contributed to the reactions. It has been argued that the toxic effects or reactions to propanidid (and Althesin) were due to the drugs themselves. Several cases of negative reactions have been recorded for different drugs using Cremophor EL as solubilizer. This suggest that the negative reactions were mainly caused by Cremophor and not by the drug substances themselves. Propanidid is presumed to work as a GABA receptor agonist.

CNS Activity

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
26.0 µM [EC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
Epontol

PubMed

Sample Use Guides

In Vivo Use Guide
The dose required to inhibit the reflex in 95% of patients was 7.22 mg kg-1 and prevented adrenergic responses to nociceptive stimulation. The dose of propanidid required to induce loss of nystagmus was greater than that necessary to abolish response to verbal command. The reflex inhibition rate increased proportionally to the dose up to 8 mg kg-1; larger doses exerted a facilitatory effect and reduced the reflex inhibition rate.
Route of Administration: Intravenous
In Vitro Use Guide
Propanidid potentiated the GABA (5 uM; EC20 concentration)-mediated current (EC50 values of 26 uM). Propanidid (50 uM) produced >50% inhibition of specific binding at GABAA chloride channels (65%).