Pytka Karolina, Rapacz Anna, Zygmunt Małgorzata, Olczyk Adrian, Waszkielewicz Anna, Sapa Jacek, Filipek Barbara
Department of Pharmacodynamics, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland.
Department of Pharmacodynamics, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland.
Pharmacol Rep. 2015 Feb;67(1):160-5. doi: 10.1016/j.pharep.2014.08.016. Epub 2014 Aug 27.
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 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.
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.
所研究的化合物：3-氯-5-{[4-(2-羟乙基)哌嗪-1-基]甲基}-9H-呫吨-9-酮二盐酸盐（HBK-6）是一种新型呫吨酮衍生物。在本研究中，我们研究了其抗抑郁样特性及可能的作用机制。
在小鼠强迫游泳试验（FST）中评估抗抑郁样活性。分析对小鼠运动活性的影响，以确定在FST中观察到的效应是否具有特异性。采用转棒试验确定神经毒性特性。
HBK-6在5和10mg/kg剂量时可减少小鼠在FST中的不动时间，而氟西汀（FX）在15mg/kg、瑞波西汀（RX）在10mg/kg和安非他酮（BPR）在5mg/kg时也有此作用。联合给予亚有效剂量的HBK-6和FX可减少小鼠在FST中的不动时间，但联合RX或BPR则无此作用。用对氯苯丙氨酸预处理后，5mg/kg剂量的HBK-6在FST中未显示活性。所研究的呫吨酮衍生物在5和10mg/kg剂量时未损害小鼠的运动协调性。
我们证明HBK-6在FST中具有强效抗抑郁样活性，比FX和RX更强，且似乎通过5-羟色胺能系统介导其作用。此外，在抗抑郁样剂量下它不显示神经毒性特性。鉴于这些有前景的结果，HBK-6在抑郁症治疗中可能具有潜力，但这需要进一步研究。
