Modulation of human GABAA and glycine receptor currents by menthol and related monoterpenoids

Eur J Pharmacol. 2004 Dec 3;506(1):9-16. doi: 10.1016/j.ejphar.2004.10.026.


Effects of common monoterpenoid alcohols and ketones were investigated on recombinant human gamma-aminobutyric acid A (GABAA; alpha1beta2gamma2s) and glycine (alpha1 homomers) receptors expressed in Xenopus oocytes. GABA currents were enhanced by coapplications of 10-300 microM: (+)-menthol>(-)-menthol>(-)-borneol>>(-)-menthone=camphor enantiomers>carvone enantiomers, with menthol acting stereoselectively. By contrast, thujone diastereomers inhibited GABAA receptor currents while glycine currents were only markedly potentiated by menthol. Positive modulation by (+)-menthol was explored given its pronounced effects (e.g., at 100 microM, GABA and glycine EC20 responses increased by 496+/-113% and 135+/-56%, respectively). (+)-Menthol, 100 microM, reduced EC50 values for GABA and glycine from 82.8+/-9.9 to 25.0+/-1.8 microM, and from 98.7+/-8.6 to 75.7+/-9.4 microM respectively, with negligible effects on maximal currents. This study reveals a novel neuroactive role for menthol as a stereoselective modulator of inhibitory ligand-gated channels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Female
  • Gene Expression
  • Glycine / pharmacology
  • Humans
  • Membrane Potentials / drug effects
  • Menthol / chemistry
  • Menthol / pharmacology*
  • Monoterpenes / pharmacology*
  • Oocytes / drug effects
  • Oocytes / physiology
  • Patch-Clamp Techniques
  • Receptors, GABA-A / genetics
  • Receptors, GABA-A / physiology*
  • Receptors, Glycine / genetics
  • Receptors, Glycine / physiology*
  • Stereoisomerism
  • Xenopus
  • gamma-Aminobutyric Acid / pharmacology


  • Monoterpenes
  • Receptors, GABA-A
  • Receptors, Glycine
  • Menthol
  • gamma-Aminobutyric Acid
  • Glycine