title: 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.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Pharmacy, Birla Institute of Technology and Science (BITS), Pilani, Rajasthan, India.
authors.forename: Radhakrishnan
authors.initials: R
authors.lastname: Mahesh
authors.forename: Baldev
authors.initials: B
authors.lastname: Kumar
authors.forename: Ankur
authors.initials: A
authors.lastname: Jindal
authors.forename: Shvetank
authors.initials: S
authors.lastname: Bhatt
authors.forename: Thangaraj
authors.initials: T
authors.lastname: Devadoss
authors.forename: Dilip Kumar
authors.initials: DK
authors.lastname: Pandey
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000737:chemistry / Q000627:therapeutic use*; D003863:Depression / Q000188:drug therapy* / Q000523:psychology; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D010879:Piperazines / Q000737:chemistry / Q000627:therapeutic use*; D011810:Quinoxalines / Q000737:chemistry / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000737:chemistry / Q000627:therapeutic use*
chemical_list: C000599654:(4-phenylpiperazin-1-yl)(quinoxalin-2-yl)methanone; D000928:Antidepressive Agents; D010879:Piperazines; D011810:Quinoxalines; D058831:Serotonin 5-HT3 Receptor Antagonists
keywords: (4-phenylpiperazin-1-yl) (quinoxalin-2-yl) methanone; 4a; 5-HT3 receptor antagonist; depression; forced swim test; olfactory bulbectomy