Key result
Nitazene opioids inhibit cardiac hERG channels, with protonitazene prolonging simulated APD90 by ~71%.
Why the study?
Limited information exists on the toxic effects of nitazene synthetic opioids aside from respiratory depression, and research availability of these drugs is restricted.
Do illicit nitazene synthetic opioids inhibit the cardiac hERG potassium channel and prolong action potential duration in computational human heart models?
Do illicit nitazene synthetic opioids inhibit the cardiac hERG potassium channel and prolong action potential duration in computational human heart models?
This computational study identifies the cardiac hERG potassium channel as a likely target of illicit nitazene opioids at low micromolar concentrations, highlighting an unrecognized proarrhythmic risk in nitazene overdoses and polydrug use.
Answers are grounded in this paper and cite their sources.
Suggests unrecognized proarrhythmic risk in nitazene overdoses; hypothesis-generating and requires experimental validation before clinical relevance.
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 50 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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Hancox et al. (2024) studied Nitazene opioid cardiotoxicity / proarrhythmia (n=5). Nitazene opioids (etonitazene, isotonitazene, metonitazene, protonitazene, and brorphine) vs. Fentanyl (positive control for hERG potency prediction) and control action potential simulations was evaluated on Predicted hERG potassium channel inhibition (IC50) and simulated action potential duration at 90% repolarization (APD90) prolongation. Nitazene opioids were predicted to inhibit cardiac hERG channels with IC50 values of 1.25-4.71 μM, with 3.41 μM protonitazene prolonging simulated ventricular APD90 by 70.9%.
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