Antidepressant-like effect of novel 5-HT3 receptor antagonist N-n-butyl-3-ethoxyquinoxalin-2-carboxamide (6p): An approach using rodent behavioral antidepressant tests

Abstract

Objective:The present study was designed to investigate the antidepressant potential of N-n-butyl-3-ethoxyquinoxalin-2-carboxamide (6p), a novel 5-HT3 receptor antagonist in rodent behavioral models of depression.Materials and Methods:The compound 6p was examined in various behavioral models like forced swim test (FST), tail suspension test (TST), mechanistic models [5-hydroxytryptophan (5-HTP)-induced head twitch and reserpine-induced hypothermia (RIH)], and in chronic surgery model-olfactory bulbectomy in rats.Results:Compound 6p (1, 2, and 4 mg/kg, i.p.) exhibited antidepressant-like effect in FST and TST after acute treatment without having an effect on baseline locomotor activity. Moreover, 6p (2 mg/kg, i.p.), potentiated the 5-HTP–induced head twitch responses in mice and inhibited the RIH in rats. Chronic treatment (14 days) with 6p (1 and 2 mg/kg, p.o.) and paroxetine (10 mg/kg, p.o.) in rats significantly reversed the behavioral anomalies induced by bilateral olfactory bulbectomy using open field exploration.Conclusion:The preliminary studies reveal that compound 6p exhibits antidepressant-like effect in behavioral rodent models of depression.