Old Drugs and New Challenges: A Narrative Review of Nitazenes

Abstract

Nitazenes are a group of compounds developed in the 1950s as opioid analgesics, but they were never approved to market. As such, they are not well known outside of academic research laboratories. A characteristic of nitazenes is their high potency (e.g., hundreds to thousands fold more potent than morphine and other opioids and tenfold more potent than fentanyl). In the past few years, several nitazenes, including "designer analogs," have been detected in the illicit drug supply and have been implicated in overdose mortality, primarily due to their exceptionally high potency. In the street drug supply, nitazenes are often found mixed with fentanyl or other agents but their presence is not always disclosed to drug buyers, who may not even be familiar with nitazenes. These drugs pose a particular challenge since there is little experience in how to reverse a nitazene overdose or potential drug-drug or drug-alcohol interactions. Public health efforts are needed to better inform street drug consumers, first responders, healthcare professionals, and the general public about these "new old drugs" that are infiltrating the recreational drug supply.

Seized drug reporting of NPS helps to guide regional toxicological practice: A 17 month review between 2022 and 2023

“…were the only other NSO in the top 10. Nitazenes, initially developed as high potency analgesics, also recently emerged on the drug market, with some compounds of the subclass that are 100-1000 times more potent than morphine and 10 times more than fentanyl [13]. Several compounds of the nitazene subclass of NSO have been reported in toxicological samples, including metonitazene, protonitazene, and others [14].…”

Detecting novel psychoactive substances around the world

“…A concomitant quantitative analysis of N-piperidinyl-etonitazene via LC-HRMS revealed concentrations of 1.21 ng/ml in serum and 0.51 ng/ml in urine. In light of the spread of opioids in the United States and their online availability, it is most likely that further hazardous compounds are present in the northern American territory [35].…”

Taking the pain out of pain

“…The increase in internet sourcing of opioids is also concerning due to the increase in high-potency synthetic opioids that are available in online marketplaces. Recent analyses of illicit opioid samples have demonstrated the presence of high-potency synthetic opioids such as, nitazenes which have higher potency and toxicity than fentanyl ( Pergolizzi et al, 2023 ). We should be mindful however, not to perpetuate widespread panic of a UK based opioid epidemic.…”