Rivastigmine, which is a cholinesterase inhibitor used for the treatment of mild to moderate Alzheimer's disease, is known to be associated with significant gastrointestinal (GI) adverse reactions including nausea, vomiting, anorexia. If severe GI adverse reactions are observed during the course of treatment, the patient should be instructed to stop treatment. Rikkunshi-To (RKT), a traditional herbal Japanese medicine, has been prescribed for patients with various GI symptoms, and we have reported that RKT on therapy-induced nausea in mice. We also reported that pica, kaolin ingestion behavior, could be used to evaluate nausea in mice; thus, in this study, we investigated the effects of rivastigmine on pica in mice and the effects of RKT on inhibition of rivastigmine-induced nausea.
Male mice were consecutively administered rivastigmine (i.p.) for 5 days, and their kaolin intakes were measured. Additionally, we examined the effects of a serotonin 5-HT₃ (granisetron: i.p.), dopamine D₂ (domperidone: i.p.) and muscarinic (butylscopolamine: i.p.) receptor antagonists rivastigmine-induced pica. Furthermore, we investigated whether RKT has the therapeutic effects on the rivastigmine-induced pica. 
We found mice showed pica during the course of donepezil administration. Among the tested anti-emetic drugs, none of the anti-emetic drugs led to any change in the rivastigmine-induced pica. On the other hand, mice fed the diet supplemented with RKT significantly inhibited rivastigmine-induced pica. These findings suggest that RKT is useful to prevent rivastigmine-induced nausea.