Anti-depressant - Like Effect of Novel 5-HT Receptor Antagonist, (4- 3 benzylpiperazin-1-yl) (3-methoxyquinoxalin-2-yl)methanone (6g) in Acute and Chronic Animal Models of Depression
Radhakrishnan Mahesh1, Shvetank Bhatt1★, Thangaraj Devadoss1, Ankur Kumar Jindal1, Baldev Kumar Gautam1, Arghya Kusum Dhar1, Dilip Kumar Pandey1★ Corresponding author
- 1Department of Pharmacy, FD-III, Birla Institute of Technology & Science, Pilani, Rajasthan-333031, India.
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Shvetank Bhatt
Department of Pharmacy, FD-III, Birla Institute of Technology & Science, Pilani, Rajasthan-333031, India.
Received: 24-01-2012; Revised: 28-05-2012; Accepted: 08-10-2012.
Volume 47, Issue 1 · pp. 71–81 · PUBLISHED 2013 · DOI:
ABSTRACT
novel 5-HT receptor antagonist '6g' with a good log P and pA value identified from a series of compounds synthesized in our laboratory was subjected to forced 3 2 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.
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Mahesh, R., Bhatt, S., Devadoss, T., Jindal, A. K., Gautam, B. K., Dhar, A. K., & Pandey, D. K. (2013). Anti-depressant - Like Effect of Novel 5-HT Receptor Antagonist, (4- 3 benzylpiperazin-1-yl) (3-methoxyquinoxalin-2-yl)methanone (6g) in Acute and Chronic Animal Models of Depression. Indian Journal of Pharmaceutical Education and Research, 47(1), 71–81.