PHARMACOLOGY
Year : 2012  |  Volume : 4  |  Issue : 4  |  Page : 235-244

Antidepressant potential of 5-HT 3 receptor antagonist, N-n- propyl-3-ethoxyquinoxaline-2-carboxamide (6n)


Department of Pharmacy, FD-III, Birla Institute of Technology and Science, Pilani, Rajasthan, India

Correspondence Address:
S Bhatt
Department of Pharmacy, FD-III, Birla Institute of Technology and Science, Pilani, Rajasthan
India
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DOI: 10.4103/0975-1483.104367

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The present study was designed to evaluate the antidepressant potential of 5-HT3 receptor antagonist N-n-propyl-3-ethoxyquinoxaline-2-carboxamide ( 6n). The compound ' 6n' with optimum log P and pA 2 value identified from a series of compounds synthesized in our laboratory was subjected to forced Swim Test (FST) (1, 2, and 4 mg/kg, i.p) and Tail Suspension Test (TST) (1, 2, and 4 mg/kg, i.p.). The compound ' 6n' significantly reduced the duration of immobility in mice without affecting the baseline locomotion. Moreover, ' 6n' (2 mg/kg, i.p.) potentiated the 5-hydroxytryptophan (5-HTP)-induced head twitch responses in mice and ' 6n' at tested dose (1 and 2 mg/kg, i.p.) reversed the reserpine-induced hypothermia in rats. In interaction studies of ' 6n' with various standard drugs/ligands using FST, ' 6n' (1 mg/kg, i.p.) potentiated the antidepressant effect of venlafaxine (4 and 8 mg/kg, i.p.) and fluoxetine (10 and 20 mg/kg, i.p.). Additionally, ' 6n' (1 and 2 mg/kg, i.p.) influenced the effect of harmane (5 mg/ kg, i.p.) as well as reversed the effect of parthenolide (1 mg/kg, i.p.) by reducing the duration of immobility in FST. Furthermore, ' 6n' (1 mg/kg, i.p.) potentiated the effect of bupropion (10 and 20 mg/kg, i.p.) in TST. Chronic ' 6n' (1 and 2 mg/kg, i.p.) treatment attenuated the behavioral abnormalities in olfactory bulbectomized rats. In conclusion, these various findings reiterated the antidepressant-like effects of ' 6n' in behavioral models of depression.


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