Nitazene opioids and the heart: Identification of a cardiac ion channel target for illicit nitazene opioids

Jules C. Hancox , Yibo Wang , Caroline S. Copeland , Henggui Zhang , Stephen C. Harmer , Graeme Henderson
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Abstract

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 IC50 values. These findings indicate a potential for proarrhythmic hERG block by nitazene opioids, warranting detailed cardiac safety evaluations of these drugs.

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硝氮烯类阿片与心脏:识别非法硝氮烯类阿片的心脏离子通道靶点
硝氮合成阿片类药物的使用日益增多,预示着阿片类药物危机进入了一个新阶段。然而,除了呼吸抑制倾向外,有关这些药物毒性作用的信息十分有限。由于对硝氮类药物的研究有限,我们使用基于机器学习的工具评估了五种硝氮类化合物与 hERG 钾通道的相互作用潜力。据预测,所有硝氮类化合物都能以较低的μM IC50值抑制hERG。这些研究结果表明,硝氮烯类阿片类药物可能会阻断hERG,从而导致心律失常,因此需要对这些药物进行详细的心脏安全性评估。
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Journal of molecular and cellular cardiology plus
Journal of molecular and cellular cardiology plus Cardiology and Cardiovascular Medicine
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