Objective: Chemotherapy-induced nausea and vomiting (CINV) following antineoplastic drug administration in cancer patients significantly affects their quality of life and treatment adherence. The 5-hydroxytryptamine type 3A receptor (5-HT3A) (serotonin) is a key target involved in emetic signaling. Understanding the molecular interactions between chemotherapeutic agents and this receptor may aid in the development of more effective antiemetic therapies. This study aims to investigate the binding potential of commonly used chemotherapeutic drugs to the serotonin receptor to better understand their role in triggering emetic responses.
Materials and Methods: A computer-aided protein-ligand docking analysis was performed using AutoDock4 and PyMol software to evaluate drug-receptor binding affinities. Frequently used chemotherapeutic agents (azacitidine, carboplatin, cyclophosphamide, dacarbazine, doxorubicin, lomustine, melphalan, and streptozocin) and standard antiemetics were analyzed in experimental groups, with serotonin used as a control in the computational study.
Results: The chemotherapeutic agents demonstrated significantly higher binding potential compared to antiemetics and serotonin. Notably, these antineoplastic drugs were shown, for the first time, to interact with common amino acids, antiemetics, and serotonin, suggesting that chemotherapy drugs might compete with them for binding to the 5-HT3A receptor and thereby exacerbate nausea and vomiting during chemotherapy administration.
Conclusion: Chemotherapy-induced nausea and vomiting are known to result indirectly from serotonin released by damaged intestinal cells in response to the toxic side effects of chemotherapy drugs. However, this study remarkably proposes an alternative mechanism for CINV and presents the first evidence of a direct interaction between certain antineoplastic drugs and the serotonin receptor.