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 RESEARCH ARTICLE
Year : 2012  |  Volume : 44  |  Issue : 5  |  Page : 560-565

Antidepressant-like activity of (4-phenylpiperazin-1-yl) (quinoxalin-2-yl) methanone (4a), a novel 5-HT 3 receptor antagonist: An investigation in behaviour-based rodent models of depression


Department of Pharmacy, Birla Institute of Technology and Science (BITS), Pilani, Rajasthan, India

Correspondence Address:
Baldev Kumar
Department of Pharmacy, Birla Institute of Technology and Science (BITS), Pilani, Rajasthan
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0253-7613.100371

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Aim: The present study was designed to investigate the antidepressant potential of (4-phenylpiperazin-1-yl) (quinoxalin-3-yl) methanone (4a), a novel 5-HT 3 receptor antagonist, with an optimal log P (2.84) and pA 2 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.






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