title: Antidepressant-like activity of a new piperazine derivative of xanthone in the forced swim test in mice: The involvement of serotonergic system.
abstract: BACKGROUND
  The studied compound: 3-chloro-5-{[4-(2-hydroxyethyl)piperazin-1-yl]methyl}-9H-xanthen-9-one dihydrochloride (HBK-6) is a new xanthone derivative. In this study we investigated its antidepressant-like properties and possible mechanism of action.
  
  
  METHODS
  Antidepressant-like activity was evaluated in the forced swim test (FST) in mice. The influence on locomotor activity in mice was analyzed to determine whether the observed in FST effect is specific. Rotarod test was used to determine neurotoxic properties.
  
  
  RESULTS
  HBK-6 reduced immobility time in mice in FST at the doses 5 and 10mg/kg, whereas fluoxetine (FX) at 15 mg/kg, reboxetine (RX) at 10mg/kg and bupropion (BPR) at 5mg/kg. Joint administration of sub-effective doses of HBK-6 and FX, but not RX or BPR, reduced immobility in mice in FST. HBK-6 at the dose 5mg/kg did not show activity in FST after pretreatment with p-chlorophenylalanine. The studied xanthone derivative at the doses 5 and 10mg/kg did not impair motor coordination in mice.
  
  
  CONCLUSIONS
  We demonstrated that HBK-6 has a potent antidepressant-like activity in FST, stronger than that of FX and RX, and seems to mediate its effect through serotonergic system. Moreover, at antidepressant-like doses it does not show neurotoxic properties. Given the promising results, HBK-6 may have potential in the treatment of depression, but this needs extended studies.
authors.affiliation: Department of Pharmacodynamics, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland. Electronic address: karolina.pytka@uj.edu.pl.
authors.forename: Karolina
authors.initials: K
authors.lastname: Pytka
authors.affiliation: Department of Pharmacodynamics, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Rapacz
authors.affiliation: Department of Pharmacodynamics, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Zygmunt
authors.affiliation: Institute of Automatic Control, Silesian University of Technology, Gliwice, Poland.
authors.forename: Adrian
authors.initials: A
authors.lastname: Olczyk
authors.affiliation: Department of Bioorganic Chemistry, Chair of Organic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Waszkielewicz
authors.affiliation: Department of Pharmacodynamics, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Sapa
authors.affiliation: Department of Pharmacodynamics, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Filipek
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D016642:Bupropion / Q000494:pharmacology; D003866:Depressive Disorder / Q000188:drug therapy* / Q000523:psychology*; D010134:Fenclonine / Q000494:pharmacology; D005473:Fluoxetine / Q000494:pharmacology; D008297:Male; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D004856:Postural Balance / Q000187:drug effects; D000077593:Reboxetine; D012701:Serotonin / Q000502:physiology*; D018490:Serotonin Agents / Q000494:pharmacology; D013550:Swimming / Q000523:psychology*; D044004:Xanthones / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D000928:Antidepressive Agents; D009025:Morpholines; D010879:Piperazines; D018490:Serotonin Agents; D044004:Xanthones; D005473:Fluoxetine; D016642:Bupropion; D012701:Serotonin; D000077593:Reboxetine; D010134:Fenclonine
keywords: Antidepressant-like activity; Neurotoxicity; Piperazine derivative; Serotonergic system; Xanthone derivative