Menthol suppresses nicotinic acetylcholine receptor functioning in sensory neurons via allosteric modulation

Chem Senses. 2012 Jun;37(5):463-9. doi: 10.1093/chemse/bjr128. Epub 2012 Jan 25.


In this study, we have investigated how the function of native and recombinant nicotinic acetylcholine receptors (nAChRs) is modulated by the monoterpenoid alcohol from peppermint (-) menthol. In trigeminal neurons (TG), we found that nicotine (75 μM)-activated whole-cell currents through nAChRs were reversibly reduced by menthol in a concentration-dependent manner with an IC₅₀ of 111 μM. To analyze the mechanism underlying menthol's action in more detail, we used single channel and whole-cell recordings from recombinant human α4β2 nAChR expressed in HEK tsA201 cells. Here, we found a shortening of channel open time and a prolongation of channel closed time, and an increase in single channel amplitude leading in summary to a reduction in single channel current. Furthermore, menthol did not affect nicotine's EC₅₀ value for currents through recombinant human α4β2 nAChRs but caused a significant reduction in nicotine's efficacy. Taken together, these findings indicate that menthol is a negative allosteric modulator of nAChRs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials
  • Allosteric Regulation
  • Animals
  • Cell Line
  • Humans
  • Mentha piperita / chemistry
  • Menthol / pharmacology*
  • Nicotine / pharmacology*
  • Patch-Clamp Techniques
  • Rats
  • Rats, Wistar
  • Receptors, Nicotinic / metabolism*
  • Sensory Receptor Cells / cytology
  • Sensory Receptor Cells / drug effects*
  • Sensory Receptor Cells / physiology
  • Transfection
  • Trigeminal Nerve / cytology
  • Trigeminal Nerve / drug effects*
  • Trigeminal Nerve / physiology


  • Receptors, Nicotinic
  • nicotinic receptor alpha4beta2
  • Menthol
  • Nicotine