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

doi:10.1016/j.jmccpl.2024.100118

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

J Mol Cell Cardiol Plus. 2024 Dec:10:100118. doi: 10.1016/j.jmccpl.2024.100118.

Authors

Jules C Hancox^{1

2}, Yibo Wang², Caroline S Copeland^{3

4}, Henggui Zhang², Stephen C Harmer¹, Graeme Henderson¹

Affiliations

¹ School of Physiology, Pharmacology and Neuroscience, Biomedical Sciences Building, University Walk, Bristol BS8 1TD, UK.
² Biological Physics Group, Department of Physics and Astronomy, The University of Manchester, M13 9PL, UK.
³ Centre for Pharmaceutical Medicine Research, Institute of Pharmaceutical Science, King's College London, 150 Stamford Street, London SE1 9NH, UK.
⁴ National Programme on Substance Use Mortality, London, UK.

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.

Keywords: Etonitazene; Isotonitazene; Long QT; Metonitazene; Nitazene; Opioid; Protonitazene; QT interval; Torsades de pointes; hERG.