In Vivo Evaluation of Psoralen in a Copper Sulfate–Induced Chick ( <i>Gallus gallus domesticus</i> ) Emesis Model and In Silico Analysis of Its Interaction With D ₂ , 5‐HT ₃ _A , and Muscarinic Receptors

Psoralen (PSN), a naturally occurring furocoumarin, was evaluated for its antiemetic potential using integrated in vivo and in silico approaches, considering the limitations of currently available antiemetic agents. The antiemetic activity of PSN was investigated in a copper sulfate–induced emesis model using 2‐day‐old chicks ( Gallus gallus domesticus ). A dose‐dependent experimental design was employed with PSN (5, 10, and 20 mg/kg), alongside standard antiemetics (domperidone 6 mg/kg, ondansetron (OND) 5 mg/kg, and hyoscine 21 mg/kg) and combination treatments. Latency to first retch and total retching episodes were recorded, and percentage inhibition was calculated. Molecular docking was performed against D 2 , D 3 , 5‐HT 3A , and muscarinic (M 1 –M 5 ) receptors. ADMET and toxicity profiles were predicted using SwissADME and ProTox‐3.0. PSN produced a significant, dose‐dependent reduction in retching. The 20 mg/kg dose showed 65.60% inhibition of retches compared to control. Combination treatment with OND further enhanced inhibition (65.60%). Docking analysis revealed that PSN exhibited the strongest binding affinity toward the D 2 receptor (−8.8 kcal/mol), followed by M 5 (−8.1 kcal/mol) and 5‐HT 3A (−7.7 kcal/mol). Pharmacokinetic prediction indicated high gastrointestinal absorption and favorable drug‐likeness properties. PSN demonstrates significant antiemetic activity in a validated chick emesis model, supported by moderate binding affinity toward key emesis‐related receptors. While docking findings suggest possible receptor interactions, further mechanistic and translational studies are required to confirm the molecular basis of its activity.