Antidepressant-like activity of a new piperazine derivative of xanthone in the forced swim test in mice: The involvement of serotonergic system

• Published in: Pharmacological reports 2015-02, Vol.67 (1), p.160-165
• Main Authors: Pytka, Karolina, Rapacz, Anna, Zygmunt, Małgorzata, Olczyk, Adrian, Waszkielewicz, Anna, Sapa, Jacek, Filipek, Barbara
• Format: Article
• Language: English
• Subjects: Animals; Antidepressant-like activity; Antidepressive Agents - pharmacology; Bupropion - pharmacology; Depressive Disorder - drug therapy; Depressive Disorder - psychology; Drug Safety and Pharmacovigilance; Fenclonine - pharmacology; Fluoxetine - pharmacology; Male; Mice; Morpholines - pharmacology; Motor Activity - drug effects; Neurotoxicity; Original Research Article; Pharmacotherapy; Pharmacy; Piperazine derivative; Piperazines - pharmacology; Postural Balance - drug effects; Reboxetine; Serotonergic system; Serotonin - physiology; Serotonin Agents - pharmacology; Swimming - psychology; Xanthone derivative; Xanthones - chemical synthesis; Xanthones - pharmacology
• ISSN: 1734-1140; 2299-5684
• DOI: 10.1016/j.pharep.2014.08.016

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. 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. HBK-6 reduced immobility time in mice in FST at the doses 5 and 10mg/kg, whereas fluoxetine (FX) at 15mg/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. 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.