Computational, molecular modelling and anxiolytic potential of 5-HT₃ receptor antagonist

Serotonin-3 receptor antagonists are useful for treating nausea and vomiting induced by a variety of reasons. These have an impact on a variety of neuropsychiatric illnesses. As a result, we attempted to investigate the anxiolytic potential of the test drug,6j {2-[4-(4-nitro-phenyl)-piperazin-1-yl]-[1,8]naphthyridine-3-carbonitrile}and compare it to the typical 5-HT₃ receptor antagonist, ondansetron. To determine the drug-likeness, computational experiments were conductedusing Molinspiration and Swiss ADME and toxicity profile using ProTox-IItools. Binding affinity of the test and standard drug with the 5-HT3 receptor (pdb id: 6HIS) was assessed by in-silico molecular modelling studies using AutoDoc Vina. Anxiolytic screening was performed using mouse elevated plus maze model. Both the test and standard drugs have good pharmacokinetic (ADME) and same level of toxicity profiles. The test drug, 6j, showed better binding affinity (-8.5 vs. -7.7 kcal/mol) with the receptor protein compared to ondansetron. In anxiolytic animal model, 6jand ondansetron showed anxiolytic potential at 10 mg/kg dose.