Linalool exerts antiemetic effects via dopaminergic and serotonergic pathways: Evidence from chick model and molecular docking

Linalool (LIN), a naturally occurring monoterpene alcohol found in aromatic plants, exhibits diverse pharmacological properties, yet its antiemetic potential remains underexplored. In this study, we investigated the antiemetic efficacy of LIN using both in vivo and in silico approaches. Emesis was induced in chicks via oral administration of copper sulfate pentahydrate (50 mg/kg), and LIN was tested at doses of 25, 50, and 100 mg/kg. Its effects were compared against the standard antiemetics domperidone (DOM, 7 mg/kg) and ondansetron (OND, 5 mg/kg). Results demonstrated that LIN at 100 mg/kg significantly prolonged the emetic latency and reduced the number of retches. Notably, co-administration of LIN (50 mg/kg) with DOM significantly (p < 0.05) produced the most potent effect, yielding the highest latency and lowest number of retches, reflecting a synergistic interaction. Molecular docking studies revealed a strong binding affinity of LIN to the dopamine D2 receptor (- 6.4 kcal/mol) and moderate binding to the 5-HT3 receptor (- 5.3 kcal/mol), suggesting involvement of both dopaminergic and serotonergic mechanisms. These findings collectively indicate that LIN possesses significant antiemetic activity and may offer a plant-derived alternative for emesis control.