Etonitazepipne

Substance identification 

Etonitazepipne (IUPAC name: 2-[(4-Ethoxyphenyl)methyl]-5-nitro-1-(2- piperidin-1-ylethyl)-1H-benzoimidazole), also known as N-piperidinyl etonitazene, is a 5-nitro-2-benzylbenzimidazole synthetic opioid. 

Etonitazepipne has been described as a crystalline solid and a white-yellowish or yellow powder. It has been identified in falsified pharmaceutical opioid tablets. 

WHO review history 

Etonitazepipne 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 

The chemical structure and pharmacological effects of etonitazepipne closely resemble those of etonitazepyne, which is controlled under Schedule I of the Single Convention on Narcotic Drugs of 1961. 

Studies in animals have demonstrated that etonitazepipne is a full agonist at μ-opioid receptors, with greater potency than morphine. Its potency varies from less than to similar to that of fentanyl, depending on the study model. Its effects are blocked by the opioid antagonist, naltrexone. In humans, adverse effects include respiratory depression and reduced consciousness, which were reversed by naloxone. 

Dependence potential 

No controlled studies of the dependence potential of etonitazepipne 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 of other opioids such as morphine and fentanyl. 

Actual abuse and/or evidence of likelihood of abuse 

In animals, etonitazepipne showed potent opioid effects and abuse potential, similar to those of morphine and fentanyl. These effects were blocked by the opioid antagonist naltrexone. 

Non-fatal intoxications requiring hospitalization have been reported. Multiple deaths in which etonitazepipne use was analytically confirmed have been reported in at least two regions, including some in which etonitazepipne was considered the primary cause of death or no other substances were involved. Online self-reports indicate typical opioid effects, including relaxation, euphoria and sedation. 

Seizures of etonitazepipne have been reported in multiple countries and regions. 

Therapeutic usefulness 

Etonitazepipne is not known to have any therapeutic use. 

Recommendation 

Etonitazepipne (IUPAC name: 2-[(4-Ethoxyphenyl)methyl]-5-nitro-1-(2- piperidin-1-ylethyl)-1H-benzoimidazole), also referred to as N-piperidinyl etonitazene, 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 etonitazepipne (IUPAC name: 2-[(4-Ethoxyphenyl)methyl]-5-nitro-1-(2-piperidin-1-ylethyl)-1H- benzoimidazole), also referred to as N-piperidinyl etonitazene, be added to Schedule I of the 1961 Single Convention on Narcotic Drugs.