Hancox Jules C, Wang Yibo, Copeland Caroline S, Zhang Henggui, Harmer Stephen C, Henderson Graeme
School of Physiology, Pharmacology and Neuroscience, Biomedical Sciences Building, University Walk, Bristol BS8 1TD, UK.
Biological Physics Group, Department of Physics and Astronomy, The University of Manchester, M13 9PL, UK.
J Mol Cell Cardiol Plus. 2024 Dec;10:100118. doi: 10.1016/j.jmccpl.2024.100118.
The growing use of nitazene synthetic opioids heralds a new phase of the opioid crisis. However, limited information exists on the toxic effects of these drugs, aside from a propensity for respiratory depression. With restricted research availability of nitazenes, we used machine-learning-based tools to evaluate five nitazene compounds' interaction potential with the hERG potassium channel, a key drug antitarget in the heart. All nitazenes were predicted to inhibit hERG with low μM IC values. These findings indicate a potential for proarrhythmic hERG block by nitazene opioids, warranting detailed cardiac safety evaluations of these drugs.
氮杂环丁二烯合成阿片类药物的使用日益增加，预示着阿片类药物危机进入了一个新阶段。然而，除了有导致呼吸抑制的倾向外，关于这些药物的毒性作用的信息有限。由于氮杂环丁二烯的研究资源有限，我们使用基于机器学习的工具来评估五种氮杂环丁二烯化合物与hERG钾通道（心脏中一种关键的药物反靶点）的相互作用潜力。所有氮杂环丁二烯预计都能以低 microM IC 值抑制hERG。这些发现表明氮杂环丁二烯类阿片类药物有导致心律失常性hERG阻滞的可能性，因此有必要对这些药物进行详细的心脏安全性评估。
