Protonitazene

Substance identification
Protonitazene (IUPAC chemical name: N,N-Diethyl-5-nitro-2-[(4-propoxyphenyl) methyl]-1H-benzimidazole-1-ethanamine), also known as propoxynitazene, is a 5-nitro-2-benzylbenzimidazole synthetic opioid. Protonitazene has been described as a white, yellow or brown powder and as a crystalline solid.

WHO review history
Protonitazene has not been formally reviewed by WHO and is not currently under international control. Information was brought to the attention of WHO that this substance is manufactured clandestinely, poses a risk to public health and has no recognized therapeutic use.

Similarity to known substances and effects on the central nervous system
Protonitazene is a chemical analogue of metonitazene and etonitazene, which are controlled under Schedule I of the Single Convention on Narcotic Drugs of 1961. Studies in animals have demonstrated that protonitazene is a full agonist at μ-opioid receptors, with greater potency than morphine and similar potency to fentanyl. Its effects are blocked by the opioid antagonist, naltrexone.

Dependence potential
No controlled studies of the dependence potential of protonitazene in animals or humans have been reported. As it is a potent µ-opioid receptor agonist, it would be expected to produce dependence similar to other opioids such as morphine and fentanyl.

Actual abuse and/or evidence of likelihood of abuse
In animals, protonitazene showed potent opioid effects and abuse potential, similar to those of morphine and fentanyl. Its abuse potential has not been studied in humans; however, online self-reports indicate typical opioid effects, including sedation and euphoria.

Protonitazene is relatively new on the illicit drug market, and there is limited information on the prevalence of its use or of its harm. Several fatalities have occurred in which the presence of protonitazene was confirmed, usually with other substances. The number of deaths may be underreported because of limitations in testing, including difficulty in differentiating this substance from isotonitazene. Protonitazene is reported to be administered through various routes, including intranasally and intravenously.

Seizures of protonitazene have been reported in multiple countries in two regions.

Therapeutic usefulness
Protonitazene is not known to have any therapeutic use.

Recommendation
Protonitazene (IUPAC chemical name: N,N-Diethyl-5-nitro-2-[(4-propoxyphenyl) methyl]-1H-benzimidazole-1-ethanamine), also known as propoxynitazene, is a synthetic opioid that is liable to abuse and to produce ill effects similar to other opioids that are controlled under Schedule I of the 1961 Single Convention on Narcotic Drugs. Its use has been reported in a number of countries and has been associated with adverse effects, including death. It has no known therapeutic use and is likely to cause substantial harm.

Recommendation: The Committee recommended that protonitazene (IUPAC chemical name: N,N-Diethyl-5-nitro-2-[(4-propoxyphenyl)methyl]-1H- benzimidazole-1-ethanamine), also known as propoxynitazene, be added to Schedule I of the 1961 Single Convention on Narcotic Drugs.