Neuro-pharmacological evaluation of structurally novel 5-hydroxytryptamine type 3 receptor antagonist, N-n-propyl-3-ethoxyquinoxaline-2-carboxamide (6n) for its anxiolytic potential

Abstract

Aim: The present study was designed to investigate the anxiolytic activity of N-n-propyl-3-ethoxyquinoxaline-2-carboxamide (6n), a novel 5-hydroxytryptamine Type 3 (5-HT 3 ) receptor antagonist in experimental mouse models of anxiety. Materials and Methods: The anxiolytic activity of 6n (1 and 2 mg/kg, intraperitoneally (i.p.)) was evaluated in mice by using a battery of behavioral tests of anxiety such as elevated plus maze (EPM), light/dark (L and D) box, hole board (HB) and open field test (OFT) with diazepam (2 mg/kg, i.p.) as standard anxiolytic. All the tested doses of 6n did not affect the base line locomotion. Results: The new chemical entity 6n (1 and 2 mg/kg, i.p.) and diazepam (2 mg/kg, i.p.) significantly increased the percentage of time spent and number of entries in open arm in the EPM test. In the L and D test compound 6n (1 and 2 mg/kg, i.p.) and diazepam (2 mg/kg, i.p.) significantly increased the total time spent in light compartment as well as the number of transitions from one compartment to other. While 6n (2 mg/kg, i.p.), diazepam (2 mg/kg) showed a significant increase in number of square crossed and 6n at (1 mg/kg, i.p.) did not affect the number of square crossed significantly. Compound 6n (1 and 2 mg/kg, i.p.) and diazepam (2 mg/kg, i.p.) also significantly increased number of head dips and number of square crossed in HB test whereas significantly decreased the head dipping latency as compared with vehicle control group. In addition, 6n (1 and 2 mg diazepam (2 mg/kg, i.p.) significantly increased the ambulation scores and number of rearing in OFT. Conclusion: In conclusion, these findings indicated that compound 6n exhibited an anxiolytic-like effect in animal models of anxiety.