title: Antidepressant and anxiolytic-like effects of 4n, a novel 5-HT3 receptor antagonist using behaviour based rodent models.
abstract: The present study was designed to investigate the putative antidepressant and anxiolytic-like effects of N-n-Butylquinoxalin-2-carboxamide (4n), a novel 5-HT3 receptor antagonist, with an optimal log P (2.01) and pA2 value (7.3) greater than ondansetron (6.9) using rodent behavioural models of depression and anxiety. Acute treatment of 4n (1-4 mg/kg, ip) in mice produced antidepressant-like effect in forced swim test (FST) without affecting the baseline locomotion in actophotometer test in mice. 4n (2-4 mg/kg, ip) treatment also potentiated the 5-hydroxytryptophan (5-HTP) induced head twitch response in mice. Further, 4n (1-4 mg/kg, ip) treatment antagonized reserpine induced hypothermia in rats. Chronic treatment (14 days) with 4n (1-4 mg/kg) and paroxetine (10 mg/kg) significantly attenuated the behavioural anomalies induced by bilateral olfactory bulbectomy in rats in modified open field paradigm. An anxiogenic-like behaviour was induced by light alone as the stimulus using light-dark aversion test. 4n (2-4 mg/kg, ip) treatment significantly increased no. of transitions between dark and lit area and the time spent in the lit area. In conclusion, these preliminary investigations confirm that 4n exhibited antidepressant and anxiolytic-like effects in rodent models of depression and anxiety.
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science (BITS), Pilani 333 031, India. dev.nuru@gmail.com
authors.forename: Baldev
authors.initials: B
authors.lastname: Kumar
authors.forename: Ankur
authors.initials: A
authors.lastname: Jindal
authors.forename: Dilip Kumar
authors.initials: DK
authors.lastname: Pandey
authors.forename: Shvetank
authors.initials: S
authors.lastname: Bhatt
authors.forename: Thangaraj
authors.initials: T
authors.lastname: Devadoss
authors.forename: Radhakrishnan
authors.initials: R
authors.lastname: Mahesh
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage* / Q000737:chemistry; D001007:Anxiety / Q000188:drug therapy; D001522:Behavior, Animal / Q000187:drug effects; D003863:Depression / Q000188:drug therapy; D004644:Emotions / Q000187:drug effects; D051379:Mice; D009830:Olfactory Bulb / Q000601:surgery; D017294:Ondansetron / Q000627:therapeutic use; D017374:Paroxetine / Q000008:administration & dosage; D017440:Photoperiod; D011810:Quinoxalines / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D012110:Reserpine / Q000008:administration & dosage; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000008:administration & dosage / Q000737:chemistry; D013550:Swimming
chemical_list: D000928:Antidepressive Agents; C577102:N-n-butylquinoxalin-2-carboxamide; D011810:Quinoxalines; D058831:Serotonin 5-HT3 Receptor Antagonists; D017374:Paroxetine; D017294:Ondansetron; D012110:Reserpine