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Aim: The aim of the study was to evaluate a novel 5 HT 3 receptor antagonist (6g) on chronic stress induced changes in behavioural and brain oxidative stress parameter in mice. A complicated relationship exists among stressful stimuli, body's reaction to stress and the onset of clinical depression. Chronic unpredictable stressors can produce a situation similar to human depression, and such animal models can be used for the preclinical evaluation of antidepressants. Materials and Methods: In the present study, a novel and potential 5-HT3 receptor antagonist (4-benzylpiperazin-1-yl)(3-methoxyquinoxalin-2-yl) methanone (6g) with good Log P (3.08) value and pA2 (7.5) values, synthesized in our laboratory was investigated to study the effects on chronic unpredictable mild stress (CUMS)-induced behavioural and biochemical alterations in mice. Mice were subjected to different stress paradigms daily for a period of 28 days to induce depressive-like behaviour. Results: The results showed that CUMS caused depression-like behaviour in mice, as indicated by the significant (P < 0.05) decrease in sucrose consumption and locomotor activity and increase in immobility the forced swim test. In addition, it was found that lipid peroxidation and nitrite levels were significantly (P < 0.05) increased, whereas glutathione levels, superoxide dismutase and catalase activities decreased in brain tissue of CUMS-treated mice. '6g' (1 and 2 mg/kg, p.o., 21 days) and fluoxetine treatment (20 mg/kg, p.o., 21 days) signficantly (P < 0.05) reversed the CUMS-induced behavioural (increased immobility period, reduced sucrose preference and decreased locomotor activity) and biochemical (increased lipid peroxidation; decreased glutathione levels, superoxide dismutase and catalase activities). However fluoxetine treatment (20 mg/kg, p.o., 21 days) significantly decreased the nitrite level in the brain while '6g' (1 and 2 mg/kg, p.o., 21 days) did not show significant (P < 0.05) effect on the nitrite levels in brain. Conclusion: Compound '6g' exerted antidepressant-like effects in behavioural despair paradigm in chronically stressed mice by restoring antioxidant mechanisms. [ABSTRACT FROM AUTHOR]

Aim: The present study was designed to investigate the anxiolytic activity of 6g, a novel serotonin type-3 receptor (5-HT3) receptor antagonist in experimental mouse models of anxiety. Materials and Methods: The anxiolytic activity of "6g" (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&D) box, hole board (HB), and open field test (OFT) with diazepam (2 mg/kg, i.p.) as standard anxiolytic. None of the tested dose of "6g" affects the base line locomotion. Results: The new chemical entity "6g" (2 mg/kg, i.p.) and diazepam (2 mg/kg, i.p.) significantly (P < 0.05) increased the percentage of time spent and number of entries in open arm in the EPM test. In the L&D test compound "6g" (2 mg/kg, i.p.) and diazepam (2 mg/kg, i.p.) significantly (P < 0.05) increased the total time spent in light compartment as well as number of transitions from one compartment to other. Compound "6g" (1 and 2 mg/kg, i.p.) and diazepam (2 mg/kg, i.p.) also significantly (P < 0.05) increased number of head dips, whereas significantly (P < 0.05) decreased the head dipping latency in HB test as compared to vehicle control group. In addition, 6g (2 mg/kg, i.p.) and diazepam (2 mg/kg, i.p.) significantly (P < 0.05) increased the ambulation scores (square crossed) in OFT and there was no significant effect of 6g (1 and 2 mg/kg, i.p.) and diazepam (2 mg/kg, i.p.) on rearing scores. Conclusion: In conclusion, these findings indicated that compound "6g" exhibited an anxiolytic-like effect in animal models of anxiety. [ABSTRACT FROM AUTHOR]

Aim: The present study was designed to investigate the antidepressant potential of (4-phenylpiperazin-1-yl) (quinoxalin-3-yl) methanone (4a), a novel 5-HT3 receptor antagonist, with an optimal log P (2.84) and pA2 value (7.3) greater than ondansetron (6.9) using rodent behavioural models of depression. Materials and Methods: Swiss albino mice were used in actophotometer test, forced swim test (FST) and 5-hydroxytryptophan (5-HTP) induced head twitch response. Reserpine induced hypothermia (RIH) and olfactory bulbectomy were performed in male Wistar rats. Statistical analysis was carried out by using one-way analysis of variance followed by Tukey's test. Results: Acute treatment of 4a (1-4 mg/kg, i.p.) in mice produced antidepressant-like effects in FST without affecting the baseline locomotion in actophotometer test. Further, 4a (2-4 mg/kg, i.p.) potentiated the 5-HTP induced head twitches response in mice and also antagonized RIH in rats. Furthermore, sub-chronic (14 days) treatment with 4a (2-4 mg/ kg, p.o.) significantly attenuated the behavioural anomalies induced by bilateral olfactory bulbectomy in rats in modified open field exploration. Conclusions: These preliminary investigations confirm that 4a exhibits antidepressant-like activity in behaviour based rodent models of depression. [ABSTRACT FROM AUTHOR]