Yokukansan contains compounds that antagonize the 5-HT₃ receptor

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.

To evaluate the effect of seven alkaloids in Uncaria hook (hirsutine, hirsuteine, rhynchophylline, isorhynchophylline, corynoxeine, isocorynoxeine and geissoschizine methyl ether) on the hydroxytryptamine type-3 (5-HT₃) receptor ion channel.

We examined the effect of these alkaloids on the current of human 5-HT₃ receptors expressed in Xenopus laevis oocytes.

The human 5-HT₃A subunit alone for the 5-HT₃A receptor, or 5-HT₃A and 5-HT₃B subunits for the 5-HT₃AB receptor, were expressed in Xenopus laevis oocytes. The 5-HT current was measured with or without alkaloid application using a two-electrode voltage clamp.

Each alkaloid, except for geissoschizine methyl ether, weakly inhibited the 5-HT-mediated 5-HT₃A and/or 5-HT₃AB receptor current, but co-application of these seven alkaloids inhibited the current strongly.

Each alkaloid contributes to antagonism of the 5-HT₃ receptor.