Anti-depressant - Like Effect of Novel 5-HT3 Receptor Antagonist, (4-benzylpiperazin-1-yl) (3-methoxyquinoxalin-2-yl)methanone (6g) in Acute and Chronic Animal Models of Depression

A novel 5-HT3 receptor antagonist '6g' with a good log P and pA(2) value identified from a series of compounds synthesized in our laboratory was subjected to forced swim test (FST) (1 and 2 mg/kg, i.p) and tail suspension test (TST) (0.5-2 mg/kg, i.p.). Compound 6g significantly reduced the duration of immobility in mice without affecting the base line locomotion. Moreover, 6g (1 and 2 mg/kg, i.p.), potentiated the 5-hydroxytryptophan (5-HTP)-induced head twitch responses in mice and reversed the reserpine-induced hypothermia (RIH) in rats. In interaction studies of 6g with various standard drugs/ligands using FST, 6g (1 mg/kg, i.p.) potentiated the anti-depressant effect of venlafaxine, desipramine and fluoxetine. Moreover, 6g (1 and 2 mg/kg, i.p.) influenced the effect of 8-OH DPAT and harmane as well as reverse the effect of parthenolide by reducing the duration of immobility in FST. However, 6g (1 and 2 mg/kg, i.p.) has no influence on mCPP induced increase in duration of immobility in FST. Furthermore, 6g (1 mg/kg, i.p.) potentiated the effect of bupropion in TST. Chronic 6g treatment attenuated the behavioral anomalies in olfactory bulbectomy (OBX) rats. In conclusion, these various findings reiterated the anti-depressant-like effects of 6g in behavioral models of depression.