Mode of action of peppermint oil and (-)-menthol with respect to 5-HT(3) receptor subtypes: binding studies, cation uptake by receptor channels and contraction of isolated rat ileum.

Heimes K, Hauk F, Verspohl EJ

Zusammenfassung

Peppermint oil (Mentha × piperita L. (Lamiaceae) has been shown to exert potent antiemetic properties, but its mode of action has not yet been elucidated. Among its active constituents (-)-menthol is the most important. Three different in vitro models were used to investigate the effects on 5-HT3 receptors (serotonin receptor subtype): [14C]guanidinium influx into N1E-115 cells which express 5-HT3 receptors, isotonic contractions of the isolated rat ileum and equilibrium competition binding studies using a radioactively labelled 5-HT3 receptor antagonist ([3H]GR65630) (3-(5-methyl-1H-imidazol-4-yl)-1-(1-methyl-1H-indol-3-yl)-1-propanone). Both peppermint oil and (-)-menthol inhibited [14C]guanidinium influx through 5-HT3 receptor channels as well as contractions of the ileum induced by serotonin. Neither the peppermint oil nor (-)-menthol, however, was able to displace [3H]GR65630 from 5-HT3 binding sites. It may be concluded that peppermint oil and (-)-menthol exert their antiemetic effect at least partly by acting on the 5-HT3 receptor ion-channel complex, probably by binding to a modulatory site distinct from the serotonin binding site. Copyright © 2010 John Wiley & Sons, Ltd.