Yokukansan contains compounds that antagonize the 5-HT3 receptor

Background: We recently focused on alkaloids in Uncaria hook (a constituent of the Kampo medicine, yokukansan) and identified the pharmacological action of geissoschizine methyl ether on several G protein-coupled receptors. However, the functions of other identified alkaloids in Uncaria hook, including hirsutine, hirsuteine, rhynchophylline, isorhynchophylline, corynoxeine, isocorynoxeine, are not clear. Purpose: To evaluate the effect of seven alkaloids in Uncaria hook (hirsutine, hirsuteine, rhynchophylline, isorhynchophylline, corynoxeine, isocorynoxeine and geissoschizine methyl ether) on the hydroxytryptamine type3 (5-HT3) receptor ion channel. Study design: We examined the effect of these alkaloids on the current of human 5-HT3 receptors expressed in Xenopus laevis oocytes. Methods: The human 5-HT(3)A subunit alone for the 5-HT(3)A receptor, or 5-HT(3)A and 5-HT3B subunits for the 5HT(3)AB receptor, were expressed in Xenopus laevis oocytes. The 5-HT current was measured with or without alkaloid application using a two-electrode voltage clamp. Results: Each alkaloid, except for geissoschizine methyl ether, weakly inhibited the 5-HT-mediated 5-HT(3)A and/or 5-HT(3)AB receptor current, but co-application of these seven alkaloids inhibited the current strongly. Conclusion: Each alkaloid contributes to antagonism of the 5-HT3 receptor.