Poleszak Ewa, Stasiuk Weronika, Szopa Aleksandra, Wyska Elżbieta, Serefko Anna, Oniszczuk Anna, Wośko Sylwia, Świąder Katarzyna, Wlaź Piotr
Department of Applied Pharmacy, Medical University of Lublin, Chodźki 1, PL 20-093, Lublin, Poland.
Department of Human Physiology, Medical University of Lublin, Lublin, Poland.
Metab Brain Dis. 2016 Aug;31(4):803-14. doi: 10.1007/s11011-016-9810-5. Epub 2016 Feb 29.
One of the newest substances, whose antidepressant activity was shown is traxoprodil, which is a selective antagonist of the NR2B subunit of the NMDA receptor. The main goal of the present study was to evaluate the effect of traxoprodil on animals' behavior using the forced swim test (FST), as well as the effect of traxoprodil (10 mg/kg) on the activity of antidepressants, such as imipramine (15 mg/kg), fluoxetine (5 mg/kg), escitalopram (2 mg/kg) and reboxetine (2.5 mg/kg). Serotonergic lesion and experiment using the selective agonists of serotonin receptors 5-HT1A and 5-HT2 was conducted to evaluate the role of the serotonergic system in the antidepressant action of traxoprodil. Brain concentrations of tested agents were determined using HPLC. The results showed that traxoprodil at a dose of 20 and 40 mg/kg exhibited antidepressant activity in the FST and it was not related to changes in animals' locomotor activity. Co-administration of traxoprodil with imipramine, fluoxetine or escitalopram, each in subtherapeutic doses, significantly affected the animals' behavior in the FST and, what is important, these changes were not due to the severity of locomotor activity. The observed effect of traxoprodil is only partially associated with serotonergic system and is independent of the effect on the 5-HT1A and 5-HT2 serotonin receptors. The results of an attempt to assess the nature of the interaction between traxoprodil and the tested drugs show that in the case of joint administration of traxoprodil and fluoxetine, imipramine or escitalopram, there were interactions in the pharmacokinetic phase.
曲唑酮是最新发现具有抗抑郁活性的物质之一，它是N-甲基-D-天冬氨酸（NMDA）受体NR2B亚基的选择性拮抗剂。本研究的主要目的是使用强迫游泳试验（FST）评估曲唑酮对动物行为的影响，以及曲唑酮（10毫克/千克）对丙咪嗪（15毫克/千克）、氟西汀（5毫克/千克）、艾司西酞普兰（2毫克/千克）和瑞波西汀（2.5毫克/千克）等抗抑郁药活性的影响。进行了5-羟色胺能损伤以及使用5-羟色胺受体5-HT1A和5-HT2的选择性激动剂的实验，以评估5-羟色胺能系统在曲唑酮抗抑郁作用中的作用。使用高效液相色谱法（HPLC）测定受试药物的脑内浓度。结果表明，20毫克/千克和40毫克/千克剂量的曲唑酮在FST中表现出抗抑郁活性，且这与动物运动活性的变化无关。曲唑酮与亚治疗剂量的丙咪嗪、氟西汀或艾司西酞普兰联合给药，显著影响动物在FST中的行为，重要的是，这些变化并非由于运动活性的严重程度所致。观察到的曲唑酮的作用仅部分与5-羟色胺能系统相关，且独立于对5-HT1A和5-HT2 5-羟色胺受体的作用。评估曲唑酮与受试药物之间相互作用性质的尝试结果表明，在曲唑酮与氟西汀、丙咪嗪或艾司西酞普兰联合给药的情况下，在药代动力学阶段存在相互作用。
