A Comprehensive Narrative Review of Protonitazene: Pharmacological Characteristics, Detection Techniques, and Toxicology

Protonitazene (PNZ) is a synthetic opioid emerging in Europe, Australia, North America and South America with a rapidly increasing number of intoxications. To describe PNZ's pharmacological characteristics, detection methods and the clinical presentation and management of PNZ intoxications, the PubMed database was searched for original articles in English concerning PNZ in any way. All articles were read and analysed completely for their suitability for inclusion, based on the article type, integrity and its description of PNZ pharmacology, toxicology and PNZ intoxications. Of the 21 articles resulting from the search, 16 articles were included. PNZ is a μ-opioid receptor agonist that induces opioid-like effects at subnanomolar concentrations at a much higher potency than morphine and fentanyl. 4′-Hydroxy-nitazene is a shared metabolite of most nitazenes and can be detected in urine for longer than most nitazenes, providing a way to detect nitazenes without knowing the parent nitazene. PNZ is detectable in whole blood, urine, bile, gastric contents and hair using several forms of mass spectrometry at subnanomolar concentrations but is not detectable in urine using traditional opioid test strips. More reports about monointoxications of PNZ and an appropriate public health response are necessary.