新的合成大麻素和潜在的心律失常风险

Jules C. Hancox , Caroline S. Copeland , Stephen C. Harmer , Graeme Henderson
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引用次数: 0

摘要

合成大麻素受体激动剂(SCRAs)与QT间期延长有关。由于新化合物的快速出现和研究可用性的限制,关于SCRA对心脏电生成影响的临床前信息有限。我们使用了两种基于机器学习的工具来评估七种新型SCRA与hERG钾通道(一种重要的药物抗靶标)的相互作用潜力。通过两种预测工具预测5个SCRA具有阻断hERG通道的能力;ADB-FUBIATA被预测为一种强大的hERG阻断剂。ADB-5Br-INACA和ADB-4en-PINACA显示出不同的预测。这些发现突出了新型SCRA潜在的致心律失常hERG阻断,需要进行详细的安全性评估。
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New synthetic cannabinoids and the potential for cardiac arrhythmia risk

Synthetic cannabinoid receptor agonists (SCRAs) have been associated with QT interval prolongation. Limited preclinical information on SCRA effects on cardiac electrogenesis results from the rapid emergence of new compounds and restricted research availability. We used two machine-learning-based tools to evaluate seven novel SCRAs' interaction potential with the hERG potassium channel, an important drug antitarget. Five SCRAs were predicted to have the ability to block the hERG channel by both prediction tools; ADB-FUBIATA was predicted to be a strong hERG blocker. ADB-5Br-INACA and ADB-4en-PINACA showed varied predictions. These findings highlight potentially proarrhythmic hERG block by novel SCRAs, necessitating detailed safety evaluations.

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来源期刊
Journal of molecular and cellular cardiology plus
Journal of molecular and cellular cardiology plus Cardiology and Cardiovascular Medicine
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31 days
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