August 29, 2023
New Potent Synthetic Opioid—N-Desethyl Isotonitazene—Proliferating Among Recreational Drug Supply in USA

N-Pyrrolidino protonitazene is a new synthetic opioid and the latest to emerge among the nitazene analogue (or 2-benzyl benzimidazole) subclass. N-Pyrrolidino protonitazene bears structural resemblance to both protonitazene and N-pyrrolidino etonitazene, two previously encountered nitazene analogues. N-Pyrrolidino protonitazene is dissimilar in chemical structure to fentanyl. New synthetic opioids, namely the nitazene analogues, have sustained proliferation following the 2018 scheduling of fentanyl related substances. Most nitazene analogues encountered among the recreational drug supply retain opioid receptor activity and exhibit potency similar to or greater than that of fentanyl. Recently acquired in vitro pharmacological data show that N-pyrrolidino protonitazene is an active opioid with potency approximately 25 times greater than that of fentanyl [source: L. De Vrieze and C. Stove, Ghent University].

To date in August 2023, N-pyrrolidino protonitazene has been confirmed in 20 forensic toxicology cases, all of which were medicolegal death investigations. N-Pyrrolidino protonitazene was first reported by CFSRE’s NPS Discovery in January 2023; however, the date of first sample collection was as early as December 2022. Cases originated from seven states across many regions within the United States, as well as the United Kingdom. Decedent age ranged from mid-20s to mid-70s (mean: 45 years, median: 44 years). Quantitative blood concentrations for N-pyrrolidino protonitazene ranged from 0.1 to 55 ng/mL (mean: 6.9 ng/mL, median: 1.1 ng/mL). The toxicity of N-pyrrolidino protonitazene has not been examined or reported but recent association with overdoses among people who use drugs leads professionals to believe that this synthetic opioid has the potential to cause harm and is of high public health concern globally.