Geissoschizine methyl ether, a major indole alkaloid found in Uncaria hook, is a key active component of Yokukansan with psychotropic effects. It is a potent serotonin A receptor agonist and a candidate for ameliorating aggressiveness and sociality by Yokukansan.

To find the candidate ingredients, we examined competitive binding assay and [(35)S] guanosine 5'-O-(3-thiotriphosphate) (GTPγS) binding assay of seven major alkaloids in UH using Chinese hamster ovary cells expressing 5-HT(1A) receptors artificially. Only Geissoschizine methyl ether (GM) among seven alkaloids potently bound to 5-HT(1A) receptors and acted as a partial agonist. This in vitro result on GM was further demonstrated in the socially isolated mice. As did YKS and UH, GM ameliorated the isolation-induced increased aggressiveness and decreased sociality, and the effect was counteracted by coadministration of WAY-100635[1]