RESEARCH ARTICLE |
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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
Radhakrishnan Mahesh, Baldev Kumar, Ankur Jindal, Shvetank Bhatt, Thangaraj Devadoss, Dilip Kumar Pandey
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
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/0253-7613.100371
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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