title: Mode of action of peppermint oil and (-)-menthol with respect to 5-HT3 receptor subtypes: binding studies, cation uptake by receptor channels and contraction of isolated rat ileum.
abstract: 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-HT(3) receptors (serotonin receptor subtype): [(14)C]guanidinium influx into N1E-115 cells which express 5-HT(3) receptors, isotonic contractions of the isolated rat ileum and equilibrium competition binding studies using a radioactively labelled 5-HT(3) receptor antagonist ([(3)H]GR65630) (3-(5-methyl-1H-imidazol-4-yl)-1-(1-methyl-1H-indol-3-yl)-1-propanone). Both peppermint oil and (-)-menthol inhibited [(14)C]guanidinium influx through 5-HT(3) receptor channels as well as contractions of the ileum induced by serotonin. Neither the peppermint oil nor (-)-menthol, however, was able to displace [(3)H]GR65630 from 5-HT(3) binding sites. It may be concluded that peppermint oil and (-)-menthol exert their antiemetic effect at least partly by acting on the 5-HT(3) receptor ion-channel complex, probably by binding to a modulatory site distinct from the serotonin binding site.
authors.affiliation: Department of Pharmacology, Institute of Pharmaceutical and Medicinal Chemistry, Münster, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Heimes
authors.forename: Florian
authors.initials: F
authors.lastname: Hauk
authors.forename: Eugen J
authors.initials: EJ
authors.lastname: Verspohl
mesh_terms: D000818:Animals; D000932:Antiemetics / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005260:Female; D019791:Guanidine / Q000378:metabolism; D006801:Humans; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007473:Ion Channels / Q000378:metabolism; D007551:Isotonic Contraction / Q000187:drug effects; D008297:Male; D036142:Mentha piperita / Q000737:chemistry*; D008610:Menthol / Q000494:pharmacology*; D051379:Mice; D010938:Plant Oils / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D044406:Receptors, Serotonin, 5-HT3 / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000494:pharmacology; D000077526:Tropisetron
chemical_list: D000932:Antiemetics; D007093:Imidazoles; D007211:Indoles; D007473:Ion Channels; D010938:Plant Oils; D044406:Receptors, Serotonin, 5-HT3; D058831:Serotonin 5-HT3 Receptor Antagonists; C059068:GR 65630; D008610:Menthol; D012701:Serotonin; D000077526:Tropisetron; C015424:peppermint oil; D019791:Guanidine