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
{"title":"新的合成大麻素和潜在的心律失常风险","authors":"Jules C. Hancox ,&nbsp;Caroline S. Copeland ,&nbsp;Stephen C. Harmer ,&nbsp;Graeme Henderson","doi":"10.1016/j.jmccpl.2023.100049","DOIUrl":null,"url":null,"abstract":"<div><p>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.</p></div>","PeriodicalId":73835,"journal":{"name":"Journal of molecular and cellular cardiology plus","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2023-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"New synthetic cannabinoids and the potential for cardiac arrhythmia risk\",\"authors\":\"Jules C. Hancox ,&nbsp;Caroline S. Copeland ,&nbsp;Stephen C. Harmer ,&nbsp;Graeme Henderson\",\"doi\":\"10.1016/j.jmccpl.2023.100049\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>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.</p></div>\",\"PeriodicalId\":73835,\"journal\":{\"name\":\"Journal of molecular and cellular cardiology plus\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2023-09-16\",\"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/S2772976123000193\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of molecular and cellular cardiology plus","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2772976123000193","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
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。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

New synthetic cannabinoids and the potential for cardiac arrhythmia risk

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.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Journal of molecular and cellular cardiology plus
Journal of molecular and cellular cardiology plus Cardiology and Cardiovascular Medicine
自引率
0.00%
发文量
0
审稿时长
31 days
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信