Nitazenes

Nitazenes are a group of compounds developed in the 1950s as opioid analgesics, but they were never approved to market (1)

• in the late 1950s, the synthesis of 2-benzylbenzimidazole opioids led to the creation of several compounds now known collectively as nitazenes - although they do not technically meet the current United States Adopted Name (USAN) definition of an "azene" (1)
• chemical structures are distinct from the typical morphine-like phenanthrene motif and meperidine analogues like fentanyl
• they were intended to be developed as analgesics but they were never approved for any therapeutic purpose
• a characteristic of nitazenes is their high potency (1,2) - note, for comparison, fentanyl is 50x as potent as heroin (2)
  • Metonitazene is 50x as potent as heroin
  • Protonitazene is 100x as potent as heroin
  • Isotonitazene is 250x as potent as heroin
  • Etonitazene is 500x as potent as heroin
• several nitazenes, including "designer analogues," have been detected in the illicit drug supply in the last few years
  • they 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
  • in December 2023, the UK National Crime Agency reported 54 deaths in the preceding six months where nitazenes were detected in post-mortem toxicology - although it noted that this "is likely the tip of the iceberg" (2)
• nitazenes can cause fatal respiratory depression (2)
• in the UK, nitazenes have been detected in substances sold as other opioids, benzodiazepines and cannabis products (2)

References:

1. Pergolizzi J Jr, Raffa R, LeQuang JAK, Breve F, Varrassi G. Old Drugs and New Challenges: A Narrative Review of Nitazenes. Cureus. 2023 Jun 21;15(6):e40736.
2. Holland A et al. Nitazenes - heralding a second wave for the UK drug-related death crisis? Lancet Public Health (January 12th 2024).