Direct modification of the 5-HT₃ receptor current by some anticancer drugs

The serotonin (5-hydroxytryptamine) type 3 (5-HT₃) receptor is an important target in the control of emesis, and 5-HT₃ receptor antagonists are effective against the early phase chemotherapy evoked vomiting. We recently reported that the anticancer drugs irinotecan and topotecan directly modulate the 5-HT-mediated 5-HT₃ receptor current in vitro. In addition, the drug response depends on the 5-HT₃ subunit composition. Here, we explored the effects of 35 anticancer drugs on the 5-HT₃ receptor current. We microinjected Xenopus laevis oocytes with human 5-HT₃A cRNA or a combination of human 5-HT₃A and human 5-HT₃B cRNA, and performed two-electrode voltage clamp recordings of 5-HT₃A and 5-HT₃AB receptor currents in the presence of each of the 35 drugs. Over 25% of the drugs we tested inhibited or potentiated the 5-HT₃ receptor current. The drugs that modulated the 5-HT₃ receptor current had molecular weights of approximately 500. These results implied that these anticancer drugs could affect 5-HT₃ receptor.