Karolina Pytka1, Anna Rapacz2, Małgorzata Zygmunt2, Adrian Olczyk3, Anna Waszkielewicz4, Jacek Sapa2, Barbara Filipek2. 1. Department of Pharmacodynamics, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland. Electronic address: karolina.pytka@uj.edu.pl. 2. Department of Pharmacodynamics, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland. 3. Institute of Automatic Control, Silesian University of Technology, Gliwice, Poland. 4. Department of Bioorganic Chemistry, Chair of Organic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland.
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.
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: Karolina Pytka; Monika Głuch-Lutwin; Elżbieta Żmudzka; Kinga Sałaciak; Agata Siwek; Katarzyna Niemczyk; Maria Walczak; Magdalena Smolik; Adrian Olczyk; Adam Gałuszka; Jarosław Śmieja; Barbara Filipek; Jacek Sapa; Marcin Kołaczkowski; Katarzyna Pańczyk; Anna Waszkielewicz; Henryk Marona Journal: Front Pharmacol Date: 2018-10-16 Impact factor: 5.810
Authors: Karolina Pytka; Anna Partyka; Magdalena Jastrzębska-Więsek; Agata Siwek; Monika Głuch-Lutwin; Barbara Mordyl; Grzegorz Kazek; Anna Rapacz; Adrian Olczyk; Adam Gałuszka; Marian Błachuta; Anna Waszkielewicz; Henryk Marona; Jacek Sapa; Barbara Filipek; Anna Wesołowska Journal: PLoS One Date: 2015-11-10 Impact factor: 3.240
Authors: Magdalena Dudek; Kamil Kuder; Marcin Kołaczkowski; Adrian Olczyk; Elżbieta Żmudzka; Aleksandra Rak; Marek Bednarski; Karolina Pytka; Jacek Sapa; Katarzyna Kieć-Kononowicz Journal: Metab Brain Dis Date: 2016-05-24 Impact factor: 3.584
Authors: Karolina Pytka; Elżbieta Żmudzka; Klaudia Lustyk; Anna Rapacz; Adrian Olczyk; Adam Gałuszka; Anna Waszkielewicz; Henryk Marona; Jacek Sapa; Filipek Barbara Journal: Indian J Pharmacol Date: 2016 May-Jun Impact factor: 1.200