N-Pyrrolidino protonitazene

Substance identification 

N-Pyrrolidino protonitazene (IUPAC name: 2-[(4-Propoxyphenyl)methyl]-5-nitro- 1-(2-pyrrolidin-1-ylethyl)-1H-benzoimidazole), also known as protonitazepyne, is a 5-nitro-2-benzylbenzimidazole synthetic opioid. 

N-Pyrrolidino protonitazene has been described as a beige powder or a white colourless or crystalline solid. N-Pyrrolidino protonitazene has been identified in falsified pharmaceutical opioid tablets. 

WHO review history 

N-Pyrrolidino protonitazene has not previously been reviewed by WHO and is not currently under international control. Information was brought to the attention of WHO that the 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 N-pyrrolidino protonitazene closely resemble those of protonitazene, which is controlled under Schedule I of the Single Convention on Narcotic Drugs of 1961. 

Studies in animals have demonstrated that N-pyrrolidino protonitazene is a full agonist at μ-opioid receptors, with greater potency than morphine and fentanyl. Its effects are blocked by the opioid antagonist naltrexone. 

Its adverse effects, documented in clinical presentations, are also consistent with opioid effects, including dizziness, bradycardia, hypotension and respiratory depression. 

Dependence potential 

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

Actual abuse and/or evidence of likelihood of abuse 

In animals, N-pyrrolidino protonitazene showed opioid effects and abuse potential, with greater potency than fentanyl. Its abuse potential has not been studied in humans. Online self-reports describe typical opioid effects, including relaxation, euphoria and sedation. 

Its presence has been analytically confirmed in many deaths and hospital admissions, including as the only substance detected. N-Pyrrolidino protonitazene is reported to be administered by various routes, including smoking, snorting and by injection. N-Pyrrolidino protonitazene has been available for sale online by Internet retailers. 

Seizures of N-pyrrolidino protonitazene have been reported in multiple countries in three regions. 

Therapeutic usefulness 

N-Pyrrolidino protonitazene is not known to have any therapeutic use. 

Recommendation 

N-Pyrrolidino protonitazene (IUPAC name: 2-[(4-Propoxyphenyl)methyl]- 5-nitro-1-(2-pyrrolidin-1-ylethyl)-1H-benzoimidazole), also referred to as protonitazepyne, 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. Its use causes substantial harm, including death. It has no known therapeutic use. 

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