Możdżeń Edyta, Wąsik Agnieszka, Romańska Irena, Michaluk Jerzy, Antkiewicz-Michaluk Lucyna
Institute of Pharmacology, Polish Academy of Sciences, Department of Neurochemistry, Kraków, Poland.
Institute of Pharmacology, Polish Academy of Sciences, Department of Neurochemistry, Kraków, Poland.
Pharmacol Rep. 2017 Jun;69(3):566-574. doi: 10.1016/j.pharep.2017.01.032. Epub 2017 Feb 8.
Most of the currently used antidepressant drugs are monoamine-based compounds, acting by the inhibition of re-uptake or metabolism of noradrenaline (NA) and/or serotonin (5-HT), because these neurotransmitters play a key role in the pathophysiology of depression. The aim of this study was to investigate the potential antidepressant-like activity of an endogenous amine, 1,2,3,4-tetrahydroisoquinoline (TIQ) and its close derivative, 1-methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ).
The experiments were carried out on male C57BL6J mice. The antidepressant-like activity of TIQs was evaluated in the behavioral tests: the forced swim test (FST) and tail suspension test (TST) and neurochemical analysis. TIQ and 1MeTIQ were administrated in three differences doses of 10, 25 or 50mg/kg. Imipramine (IMI; 15 or 30mg/kg) was used as a reference drug. In the neurochemical ex vivo study, the levels of NA, 5-HT and their metabolites, the rate of monoamine metabolism and their neuronal activity in different mouse brain structures were determined by HPLC with electrochemical detection.
The results of this study have demonstrated that TIQ and 1MeTIQ produced antidepressant-like effect in the FST and TST because they significantly decreased the immobility time comparably to IMI. Biochemical data have demonstrated that administration of TIQs led to the activation of NA and 5-HT systems.
The results reported in this paper indicate that TIQ and 1MeTIQ possess a distinct antidepressant activity. In the light of these findings, we suggest that both tested compounds may be effective for the depression therapy in a clinical setting with better tolerance of side effects.
目前使用的大多数抗抑郁药物都是基于单胺的化合物，通过抑制去甲肾上腺素（NA）和/或血清素（5-HT）的再摄取或代谢发挥作用，因为这些神经递质在抑郁症的病理生理学中起关键作用。本研究的目的是研究内源性胺1,2,3,4-四氢异喹啉（TIQ）及其紧密衍生物1-甲基-1,2,3,4-四氢异喹啉（1MeTIQ）的潜在抗抑郁样活性。
实验在雄性C57BL6J小鼠上进行。TIQ的抗抑郁样活性在行为测试中进行评估：强迫游泳试验（FST）和悬尾试验（TST）以及神经化学分析。TIQ和1MeTIQ以10、25或50mg/kg三种不同剂量给药。丙咪嗪（IMI；15或30mg/kg）用作参考药物。在神经化学离体研究中，通过高效液相色谱-电化学检测法测定不同小鼠脑结构中NA、5-HT及其代谢物的水平、单胺代谢率及其神经元活性。
本研究结果表明，TIQ和1MeTIQ在FST和TST中产生了抗抑郁样效应，因为它们与IMI相比显著缩短了不动时间。生化数据表明，TIQ给药导致NA和5-HT系统的激活。
本文报道的结果表明，TIQ和1MeTIQ具有明显的抗抑郁活性。鉴于这些发现，我们建议这两种受试化合物在临床环境中对抑郁症治疗可能有效，且副作用耐受性更好。
