Menthol Inhibits 5-HT3 Receptor–Mediated Currents

@article{Ashoor2013MentholI5,
  title={Menthol Inhibits 5-HT3 Receptor–Mediated Currents},
  author={Abrar Ashoor and Jacob C. Nordman and Daniel Veltri and Keun-Hang Yang and Yaroslav M Shuba and Lina Tariq Al Kury and Bassem Sadek and Frank Christopher Howarth and Amarda Shehu and Nadine Kabbani and Murat Oz},
  journal={The Journal of Pharmacology and Experimental Therapeutics},
  year={2013},
  volume={347},
  pages={398 - 409}
}
The effects of alcohol monoterpene menthol, a major active ingredient of the peppermint plant, were tested on the function of human 5-hydroxytryptamine type 3 (5-HT3) receptors expressed in Xenopus laevis oocytes. 5-HT (1 μM)-evoked currents recorded by two-electrode voltage-clamp technique were reversibly inhibited by menthol in a concentration-dependent (IC50 = 163 μM) manner. The effects of menthol developed gradually, reaching a steady-state level within 10–15 minutes and did not involve G… 

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References

SHOWING 1-10 OF 125 REFERENCES
Direct noncompetitive inhibition of 5-HT(3) receptor-mediated responses by forskolin and steroids.
The Nonpsychoactive Cannabinoid Cannabidiol Inhibits 5-Hydroxytryptamine3A Receptor-Mediated Currents in Xenopus laevis Oocytes
TLDR
It is suggested that allosteric inhibition of 5-HT3 receptors by CBD may contribute to its physiological roles in the modulation of nociception and emesis.
Endogenous cannabinoid, anandamide, acts as a noncompetitive inhibitor on 5‐HT3 receptor‐mediated responses in Xenopus oocytes
TLDR
It is demonstrated that the endogenous cannabinioid anandamide inhibits the function of 5‐HT3 receptors expressed in Xenopus oocytes in a cannabinoid‐receptor independent and noncompetitive manner.
Menthol Suppresses Nicotinic Acetylcholine Receptor Functioning in Sensory Neurons via Allosteric Modulation
TLDR
Findings indicate that menthol is a negative allosteric modulator of nAChRs, which is a significant reduction in nicotine's efficacy.
Noncompetitive inhibition by camphor of nicotinic acetylcholine receptors.
The Endocannabinoid Anandamide Inhibits the Function of α4β2 Nicotinic Acetylcholine Receptors
TLDR
Results indicate that AEA directly inhibits the function of α4β2 nAChRs in a CB1 receptor-independent manner and raises the energy of the activated state.
A-Type GABA Receptor as a Central Target of TRPM8 Agonist Menthol
TLDR
It is shown that menthol reduces the excitation of rat hippocampal neurons in culture and suppresses the epileptic activity induced by pentylenetetrazole injection and electrical kindling in vivo and that hydroxyl plays a critical role in menthol enhancement of tonic GABAAR.
...
...