Isoliquiritigenin, a chalcone compound, is a positive allosteric modulator of GABAA receptors and shows hypnotic effects

Biochem Biophys Res Commun. 2011 Oct 7;413(4):637-42. doi: 10.1016/j.bbrc.2011.09.026. Epub 2011 Sep 14.


Isoliquiritigenin (ILTG) is a chalcone compound and has valuable pharmacological properties such as antioxidant, anti-inflammatory, anticancer, and antiallergic activities. Recently, the anxiolytic effect of ILTG has been reported; however, its action mechanism and hypnotic activity have not yet been demonstrated. Therefore, we investigated the hypnotic effect and action mechanism of ILTG. ILTG significantly potentiated the pentobarbital-induced sleep in mice at doses of 25 and 50mg/kg. The hypnotic activity of ILTG was fully inhibited by flumazenil (FLU), a specific gamma-aminobutyric acid type A (GABA(A))-benzodiazepine (BZD) receptor antagonist. The binding affinity of ILTG was 0.453 μM and was found to be higher than that of the reference compound, diazepam (DZP, 0.012 μM). ILTG (10(-5)M) potentiated GABA-evoked currents to 151% of the control level on isolated dorsal raphe neurons. ILTG has 65 times higher affinity for GABA(A)-BZD receptors than DZP, and the dissociation constant for ILTG was 4.0 × 10(-10)M. The effect of ILTG on GABA currents was blocked by 10(-7)M FLU and ZK-93426. These results suggest that ILTG produces hypnotic effects by positive allosteric modulation of GABA(A)-BZD receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allosteric Regulation
  • Animals
  • Benzodiazepines / pharmacology
  • Cells, Cultured
  • Chalcones / chemistry
  • Chalcones / pharmacology*
  • GABA Modulators / pharmacology*
  • Hypnotics and Sedatives / chemistry
  • Hypnotics and Sedatives / pharmacology*
  • Mice
  • Neurons / drug effects
  • Phenobarbital / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, GABA-A / chemistry
  • Receptors, GABA-A / metabolism*


  • Chalcones
  • GABA Modulators
  • Hypnotics and Sedatives
  • Receptors, GABA-A
  • Benzodiazepines
  • isoliquiritigenin
  • Phenobarbital