Jules C. Hancox , Yibo Wang , Caroline S. Copeland , Henggui Zhang , Stephen C. Harmer , Graeme Henderson
{"title":"Nitazene opioids and the heart: Identification of a cardiac ion channel target for illicit nitazene opioids","authors":"Jules C. Hancox , Yibo Wang , Caroline S. Copeland , Henggui Zhang , Stephen C. Harmer , Graeme Henderson","doi":"10.1016/j.jmccpl.2024.100118","DOIUrl":null,"url":null,"abstract":"<div><div>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<sub>50</sub> values. These findings indicate a potential for proarrhythmic hERG block by nitazene opioids, warranting detailed cardiac safety evaluations of these drugs.</div></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":"10 ","pages":"Article 100118"},"PeriodicalIF":0.0000,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of molecular and cellular cardiology plus","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2772976124000588","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
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.