Etonitazepyne

Substance identification
Etonitazepyne (IUPAC chemical name: 2-[(4-Ethoxyphenyl)methyl]-5-nitro- 1-(2-pyrrolidin-1-ylethyl)-1Hbenzoimidazole), also known as N-pyrrolidino etonitazene, is a benzimidazole-derived synthetic opioid. Etonitazepyne is found as a yellow powder and crystalline solid and has been identified in falsified pharmaceutical opioid tablets.

WHO review history
Etonitazepyne 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
Studies in animals have demonstrated that etonitazepyne is a potent, full agonist at μ-opioid receptors. In animals, it produces effects similar to those of opioids such as morphine, fentanyl and isotonitazene but with greater potency. There is limited information about the effects of etonitazepyne alone in humans.

Dependence potential
No controlled studies of the dependence potential of etonitazepyne in animals or humans have been reported. As it is a potent µ-opioid receptor agonist, it would be expected to produce dependence similarly to other opioids, such as morphine and fentanyl. Online self-reports describe tolerance and withdrawal after repeated etonitazepyne use.

Actual abuse and/or evidence of likelihood of abuse
In an animal model predictive of abuse potential, etonitazepyne was shown to produce effects that indicated greater potency compared to morphine and fentanyl, and these effects were reversed by the opioid antagonist, naltrexone.

Seizures of etonitazepyne have been reported in multiple countries in two regions. It is reported to be administered by various routes, including snorting, sniffing and oral administration. Etonitazepyne has been identified in falsified medicines, suggesting that its use may sometimes be unintentional.

Etonitazepyne is a relatively new drug on the illicit market, and there is limited information on the prevalence of its use and of its harm, although non-fatal and fatal intoxications have been documented in a number of countries. The number of deaths involving etonitazepyne has increased over a relatively short time but may be underreported because of its recent, rapid appearance.

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

Recommendation
Etonitazepyne (IUPAC chemical name: 2-[(4-Ethoxyphenyl)methyl]-5-nitro- 1-(2-pyrrolidin-1-ylethyl)-1Hbenzoimidazole), also known as N-pyrrolidino etonitazene, 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 poses a significant risk to public health.

Recommendation: The Committee recommended that etonitazepyne (IUPAC chemical name: 2-[(4-Ethoxyphenyl)methyl]-5-nitro-1-(2-pyrrolidin-1-ylethyl)- 1H-benzoimidazole), also known as N-pyrrolidino etonitazene, be added to Schedule I of the 1961 Single Convention on Narcotic Drugs.