Growth of Novel Potent Opioids (NPOs) in the Unregulated Drug Market

"Novel potent opioids (NPOs) are novel nonfentanyl opioids in the illicit opioid supply. Synthetic opioids are one of the fastest growing classes of opioids being detected in patients in the emergency department (ED) with opioid overdose (OD).1

"A subclass of synthetic opioids referred to as nitazenes contain a 2-benzylbenzimidazole structure that has μ-opioid agonism. Isotonitazene, metonitazene, and N-piperidinyl etonitazene are NPOs with a piperidine benzimidazolone structure. Brorphine is a nonnitazene NPO that is a full μ-opioid receptor agonist with a structure similar to fentanyl. NPOs possess high potency at the μ-opioid receptor and an understudied propensity for adverse health effects. Nitazenes are structurally unrelated to fentanyl, but have been found to be up to 1000-fold more potent than morphine.1

"The exact motivation to produce nitazenes and brorphine are unclear. The increased regulation of fentanyl and fentanyl analogues throughout the last decade may have led to a change in the chemical precursors required for clandestine laboratory production that were not yet regulated.1 This change in chemical precursors may have led to these newer and more potent opioids."