Yokukansan contains compounds that antagonize the 5-HT 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 type-3 (5-HT) receptor ion channel.

STUDY DESIGN

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

METHODS

The human 5-HTA subunit alone for the 5-HTA receptor, or 5-HTA and 5-HTB subunits for the 5-HTAB 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-HTA and/or 5-HTAB receptor current, but co-application of these seven alkaloids inhibited the current strongly.

CONCLUSION

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