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致幻化合物 25I-NBOMe 的神经毒性特征。

Neurotoxicological profile of the hallucinogenic compound 25I-NBOMe.

机构信息

Department of Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna, 31-343, Kraków, Poland.

Laboratory of Pharmacology and Brain Biostructure, Department of Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna, 31-343, Kraków, Poland.

出版信息

Sci Rep. 2022 Feb 21;12(1):2939. doi: 10.1038/s41598-022-07069-8.

Abstract

4-Iodo-2,5-dimethoxy-N-(2-methoxybenzyl)phenethylamine (25I-NBOMe) is a new psychoactive substance with strong hallucinogenic properties. Our previous data reported increased release of dopamine, serotonin, and glutamate after acute injections and a tolerance development in the neurotransmitters release and rats' behavior after chronic treatment with 25I-NBOMe. The recreational use of 25I-NBOMe is associated with severe intoxication and deaths in humans. There is no data about 25I-NBOMe in vivo toxicity towards the brain tissue. In this article 25I-NBOMe-crossing through the blood-brain barrier (BBB), the impact on DNA damage, apoptosis induction, and changes in the number of cortical and hippocampal cells were studied. The presence of 25I-NBOMe in several brain regions shortly after the drug administration and its accumulation after multiple injections was found. The DNA damage was detected 72 h after the chronic treatment. On the contrary, at the same time point apoptotic signal was not identified. A decrease in the number of glial but not in neural cells in the frontal (FC) and medial prefrontal cortex (mPFC) was observed. The obtained data indicate that 25I-NBOMe passes easily across the BBB and accumulates in the brain tissue. Observed oxidative DNA damage may lead to the glial cells' death.

摘要

4-碘-2,5-二甲氧基-N-(2-甲氧基苄基)苯乙胺(25I-NBOMe)是一种具有强烈致幻特性的新型精神活性物质。我们之前的数据显示,急性注射后多巴胺、血清素和谷氨酸释放增加,而慢性 25I-NBOMe 治疗后,神经递质释放和大鼠行为出现耐受。25I-NBOMe 的娱乐性使用与人类严重中毒和死亡有关。目前尚无关于 25I-NBOMe 对脑组织体内毒性的相关数据。在本文中,研究了 25I-NBOMe 穿过血脑屏障(BBB)、对 DNA 损伤、细胞凋亡诱导的影响以及皮质和海马区细胞数量的变化。在药物给药后不久,就在几个脑区发现了 25I-NBOMe 的存在,并且在多次注射后其积累了。在慢性治疗后 72 小时检测到 DNA 损伤。相反,在同一时间点未发现细胞凋亡信号。在前额皮质(FC)和内侧前额皮质(mPFC)中,观察到神经胶质细胞数量减少,但神经元细胞数量没有减少。研究结果表明,25I-NBOMe 很容易穿过血脑屏障并在脑组织中积累。观察到的氧化 DNA 损伤可能导致神经胶质细胞死亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c18/8861095/b3d9f58d64f9/41598_2022_7069_Fig1_HTML.jpg

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