Two new psychoactive substances (NPSs) classified as phenethylamines, namely 2-((2-(4-Iodo-2,5-dimethoxyphenyl)ethylamino)methyl)phenol (25I-NBOH) and 2-(((2-(4-chloro-2,5-dimethoxyphenyl)ethyl)amino)methyl)phenol (25C-NBOH), are being abused by people seeking recreational hallucinogens. These NPSs may cause serious health problems as their adverse effects are not known in most cases. Therefore, in the present study, we evaluated the cardiotoxicity of 25I-NBOH and 25C-NBOH using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, rat electrocardiography (ECG), Langendorff test, and human ether-a-go-go-related gene (hERG) assay. Furthermore, we analyzed the expression levels of p21 CDC42/RAC1-activated kinase 1 (PAK1), which is known to play various roles in the cardiovascular system. In the MTT assay, treatment with 25I-NBOH or 25C-NBOH dramatically decreased viability of H9c2 cardiomyocytes. Meanwhile, these two compounds significantly increased QT intervals and RR intervals in the rat ECG measurement. 25I-NBOH down-regulated the PAK1 protein expression in rat primary cardiomyocytes as well as H9c2 cells. However, 25C-NBOH had no effect on the PAK1 expression in H9c2 cells. In an in-depth study, 25I-NBOH inhibited potassium channels in the hERG assay, but in ex vivo test, the substance did not affect the left ventricular developed pressure (LVDP) and heart rate of the isolated rat hearts. Taken together, these results suggest that both 25I-NBOH and 25C-NBOH may have adverse cardiovascular effect. Further investigation would be needed to determine which factors mainly influence the relationship between PAK1 expression and cardiotoxicity.

两种新的精神活性物质 (NPS) 被归类为苯乙胺，即 2-((2-(4-Iodo-2,5-dimethoxyphenyl)ethylamino)methyl)phenol (25I-NBOH) 和 2-(((2-(4-氯-2,5-二甲氧基苯基）乙基）氨基）甲基）苯酚（25C-NBOH）被寻求娱乐致幻剂的人滥用。这些 NPS 可能会导致严重的健康问题，因为它们的不利影响在大多数情况下是未知的。因此，在本研究中，我们使用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四唑 (MTT) 测定法、大鼠心电图 (ECG) 评估了 25I-NBOH 和 25C-NBOH 的心脏毒性、Langendorff 测试和人类 ether-a-go-go 相关基因 (hERG) 测定。此外，我们分析了已知在心血管系统中发挥各种作用的 p21 CDC42/RAC1 激活激酶 1 (PAK1) 的表达水平。在 MTT 测定中，用 25I-NBOH 或 25C-NBOH 处理显着降低了 H9c2 心肌细胞的活力。同时，这两种化合物在大鼠心电图测量中显着增加了 QT 间期和 RR 间期。25I-NBOH 下调大鼠原代心肌细胞和 H9c2 细胞中 PAK1 蛋白的表达。然而，25C-NBOH 对 H9c2 细胞中 PAK1 的表达没有影响。在一项深入研究中，25I-NBOH 在 hERG 测定中抑制钾通道，但在离体试验，该物质不影响离体大鼠心脏的左心室发展压（LVDP）和心率。总之，这些结果表明 25I-NBOH 和 25C-NBOH 都可能对心血管产生不利影响。需要进一步调查以确定哪些因素主要影响 PAK1 表达与心脏毒性之间的关系。