It has been shown that anti-cancer drug induces secretion of serotonin (5-HT) from small intestine which activates serotonin type 3 (5-HT3) receptor to cause nausea and vomiting. In general, antagonist for 5-HT3 receptor is used as anti-emetics during chemotherapy. However, we found that anti-cancer drug irinotecan itself inhibits 5-HT-gated current through the homomeric 5-HT3A and heteromeric 5-HT3AB receptor in a concentration-dependent manner. The inhibitory effect of irinotecan on 5-HT3A receptor was more potent than that on 5-HT3AB receptor. On the other hand, SN-38. a metabolite of irinotecan, had no effect on the responsiveness. Our findings suggest that irinotecan itself could have anti-emetic activities through inhibition of the 5-HT3A and 5-HT3AB receptor. (C) 2011 Elsevier Inc. All rights reserved.