N-Desethyl istonitazene

Substance identification 

N-Desethyl isotonitazene (IUPAC name: N-Ethyl-2-[[4-(1-methylethoxy) phenyl]methyl]-5-nitro-1H-benzimidazole-1-ethanamine), also known as norisotonitazene, is a 5-nitro-2-benzylbenzimidazole synthetic opioid. 

N-Desethyl isotonitazene hydrochloride has been described as a crystalline solid. It has also been identified in falsified pharmaceuticals, in the form of round blue tablets. 

WHO review history 

N-Desethyl isotonitazene has not previously been 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 

N-Desethyl isotonitazene is a major metabolite of and has a similar chemical structure and effects to isotonitazene, which is controlled under Schedule I of the Single Convention on Narcotic Drugs of 1961. 

Studies in animals have demonstrated that N-desethyl isotonitazene is a full agonist at μ-opioid receptors, with greater potency than morphine. Its potency varies from similar to to greater than that of fentanyl, depending on the study model. 

Its effects are blocked by the opioid antagonists naltrexone and naloxone. 

Adverse effects, including analgesia, euphoria, miosis, muscle rigidity, unconsciousness, sedation, respiratory depression, coma and hypercapnia, are consistent with opioid toxicity. 

Dependence potential 

No controlled studies of the dependence potential of N-desethyl isotonitazene 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 that produced by other opioids, such as morphine and fentanyl. 

Actual abuse and/or evidence of likelihood of abuse 

In animals, N-desethyl isotonitazene showed potent opioid effects and abuse potential. Its potency was greater than that of morphine and varied from similar to to greater than that of fentanyl, depending on the study model. These effects were blocked by the opioid antagonist naltrexone. 

Many deaths and hospital admissions associated with N-desethyl isotonitazene have been reported in at least two regions, including deaths in which it was considered contributory. 

Seizures of N-desethyl isotonitazene have been reported in many countries in three regions. 

Therapeutic usefulness 

N-desethyl isotonitazene is not known to have any therapeutic use. 

Recommendation 

N-Desethyl isotonitazene (IUPAC name: N-Ethyl-2-[[4-(1-methylethoxy) phenyl]methyl]-5-nitro-1H-benzimidazole-1-ethanamine), also referred to as norisotonitazene, is a synthetic opioid that is liable to abuse and produces ill effects similar to those of other opioids that are controlled under Schedule I of the 1961 Single Convention on Narcotic Drugs. 

There is evidence that its use causes substantial harm, including death. It has no known therapeutic use. 

The Committee recommended that N-desethyl isotonitazene (IUPAC name: N-ethyl-2-[[4-(1-methylethoxy)phenyl]methyl]-5-nitro-1H-benzimidazole-1- ethanamine), also referred to as norisotonitazene, be added to Schedule I of the 1961 Single Convention on Narcotic Drugs.