IUPAC Name
7-chloro-5-(2-chlorophenyl)-1-methyl-3H-1,4-benzodiazepin-2-one
Current Scheduling Status
Year(s) and type of review / ECDD meetings
Drug Class
Recommendation (from TRS)
Substance identification
Isotonitazene (chemical name: N,N-diethyl-2-(2-(4-isopropoxybenzyl)- 5-nitro-1H-benzo[d]imidazol-1-yl)ethan-1-amine) belongs to the 2-benzylbenzimidazole group of compounds, which include the closely related opioids etonitazene, metonitazene and clonitazene. It is found in yellow, brown or off-white powder forms.
WHO review history
Isotonitazene has not previously been formally reviewed by WHO and is not currently under international control. Information was brought to WHO’s attention 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
Isotonitazene is a chemical analogue of etonitazene and clonitazene, both of which are Schedule I compounds under the Single Convention on Narcotic Drugs, 1961. Isotonitazene is a potent opioid analgesic with a rapid onset of action. Preclinical studies have demonstrated that isotonitazene is more potent than fentanyl and hydromorphone and substantially more potent than morphine. There is limited research on the effects of this compound on the central nervous system, but, given its demonstrated potency at the µ-opioid receptor, it would be expected to produce analgesia, respiratory depression and sedation.
Dependence potential
No controlled animal or human studies have been reported of the dependence potential of isotonitazene. As a potent µ-opioid agonist, it would be expected to produce dependence. An unverified online report described dependent use and withdrawal symptoms, including flu-like symptoms and anxiety.
Actual abuse and/or evidence of likelihood of abuse
No controlled studies have been reported on the abuse potential of isotonitazene, but, as it is a potent µ-opioid receptor agonist, it would be expected to produce euphoria and other effects predictive of high abuse liability.
Because of its relatively recent appearance on the illicit drug market, there is limited information on the prevalence of use of isotonitazene or of its harm. Seizures have been reported in many countries and regions. It is reported to be used through various routes, including sublingually, vaping and intravenously.
The number of deaths involving isotonitazene has increased in a short time. Deaths commonly occur after use in combination with other opioids or benzodiazepines. Deaths due to isotonitazene share features with deaths due to heroin, including evidence of injection and signs consistent with opioid overdose, such as pulmonary and/or cerebral oedema. Deaths due to isotonitazene are likely to be underreported because of its recent, rapid appearance.
Therapeutic usefulness
Isotonitazene is not known to have any therapeutic use.
Recommendation
The mechanism of action of isotonitazene (chemical name: N,N-diethyl- 2-(2-(4-isopropoxybenzyl)-5-nitro-1H-benzo[d]imidazol-1-yl)ethan-1- amine) indicates that it is liable to have similar abuse and similar ill effects as 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 isotonitazene (chemical name: N,N-diethyl-2-(2-(4-isopropoxybenzyl)-5-nitro-1H- benzo[d]imidazol-1-yl)ethan-1-amine) be added to Schedule I of the 1961 Single Convention on Narcotic Drugs.
Isotonitazene (chemical name: N,N-diethyl-2-(2-(4-isopropoxybenzyl)- 5-nitro-1H-benzo[d]imidazol-1-yl)ethan-1-amine) belongs to the 2-benzylbenzimidazole group of compounds, which include the closely related opioids etonitazene, metonitazene and clonitazene. It is found in yellow, brown or off-white powder forms.
WHO review history
Isotonitazene has not previously been formally reviewed by WHO and is not currently under international control. Information was brought to WHO’s attention 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
Isotonitazene is a chemical analogue of etonitazene and clonitazene, both of which are Schedule I compounds under the Single Convention on Narcotic Drugs, 1961. Isotonitazene is a potent opioid analgesic with a rapid onset of action. Preclinical studies have demonstrated that isotonitazene is more potent than fentanyl and hydromorphone and substantially more potent than morphine. There is limited research on the effects of this compound on the central nervous system, but, given its demonstrated potency at the µ-opioid receptor, it would be expected to produce analgesia, respiratory depression and sedation.
Dependence potential
No controlled animal or human studies have been reported of the dependence potential of isotonitazene. As a potent µ-opioid agonist, it would be expected to produce dependence. An unverified online report described dependent use and withdrawal symptoms, including flu-like symptoms and anxiety.
Actual abuse and/or evidence of likelihood of abuse
No controlled studies have been reported on the abuse potential of isotonitazene, but, as it is a potent µ-opioid receptor agonist, it would be expected to produce euphoria and other effects predictive of high abuse liability.
Because of its relatively recent appearance on the illicit drug market, there is limited information on the prevalence of use of isotonitazene or of its harm. Seizures have been reported in many countries and regions. It is reported to be used through various routes, including sublingually, vaping and intravenously.
The number of deaths involving isotonitazene has increased in a short time. Deaths commonly occur after use in combination with other opioids or benzodiazepines. Deaths due to isotonitazene share features with deaths due to heroin, including evidence of injection and signs consistent with opioid overdose, such as pulmonary and/or cerebral oedema. Deaths due to isotonitazene are likely to be underreported because of its recent, rapid appearance.
Therapeutic usefulness
Isotonitazene is not known to have any therapeutic use.
Recommendation
The mechanism of action of isotonitazene (chemical name: N,N-diethyl- 2-(2-(4-isopropoxybenzyl)-5-nitro-1H-benzo[d]imidazol-1-yl)ethan-1- amine) indicates that it is liable to have similar abuse and similar ill effects as 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 isotonitazene (chemical name: N,N-diethyl-2-(2-(4-isopropoxybenzyl)-5-nitro-1H- benzo[d]imidazol-1-yl)ethan-1-amine) be added to Schedule I of the 1961 Single Convention on Narcotic Drugs.
ECDD Recommendation
Inclusion in Schedule I of the 1961 Convention on Narcotic Drugs
Link to full TRS
9789240023024-eng.pdf1.84 MB
MS Questionnaire Report