Current Scheduling Status
Year(s) and type of review / ECDD meetings
Drug Class
Recommendation (from TRS)
Substance identification
Methoxyacetylfentanyl (2-methoxy-N-phenyl-N-[1-(2-phenylethyl)piperidin-4- yl]acetamide) is a synthetic analogue of the opioid fentanyl. Samples obtained from seizures and from other sources suggest that methoxyacetylfentanyl is available in the form of powders, liquids and tablets.
WHO review history
Methoxyacetylfentanyl has not been previously pre-reviewed or critically reviewed by the WHO ECDD. A critical review was proposed based on information brought to WHO’s attention that methoxyacetylfentanyl poses a serious risk to public health and has no recognized therapeutic use.
Similarity to known substances and effects on the central nervous system
Methoxyacetylfentanyl has a higher affinity to μ-opioid receptors than to κ- and δ-opioid receptors and has been shown to act as an agonist at the μ-opioid receptor. In animals, it produces analgesia with a potency higher than that of morphine and close to that of fentanyl. The analgesia was blocked by the opioid antagonist naltrexone, confirming its opioid mechanism of action.
The most serious acute health risk is respiratory depression, which in the case of an overdose can lead to respiratory arrest and death. This is consistent with its opioid mechanism of action.
Dependence potential
There are no studies of the dependence potential of this substance in humans or laboratory animals. However, based on its mechanism of action, methoxyacetylfentanyl would be expected to produce dependence similar to other opioid drugs.
Actual abuse and/or evidence of likelihood of abuse
In the animal drug discrimination model of subjective drug effects, methoxyacetylfentanyl produced effects similar to those of morphine. It also decreased activity levels and both the discriminative and rate-decreasing effects were blocked by the opioid antagonist naltrexone. Based on its receptor action and these effects in animal models, it would be expected that methoxyacetylfentanyl would be subject to abuse in a manner comparable to that of other opioids.
There is evidence that methoxyacetylfentanyl has been administered by injection and by nasal insufflation of powder. A large number of seizures of this substance have been reported in Europe and the United States. A number of deaths have been reported in Europe and the United States following which methoxyacetylfentanyl was detected in postmortem samples. While other drugs were also present in most of these cases, methoxyacetylfentanyl was deemed the cause of death or a major contributor to death in a significant proportion of them. Several countries have placed methoxyacetylfentanyl under national control.
Therapeutic usefulness
Methoxyacetylfentanyl is not known to have any therapeutic use.
Recommendation
The Committee considered that methoxyacetylfentanyl is a substance with high abuse liability and dependence potential. It is an opioid agonist that is more potent than morphine and its use has contributed to a large number of deaths in different regions. It has no therapeutic use and it poses a significant risk to public health. The Committee considered that the evidence of its abuse warrants placement under international control.
■■ Recommendation: The Committee recommended that methoxyacetylfentanyl (2-methoxy-N-phenyl-N-[1-(2-phenylethyl) piperidin-4-yl] acetamide) be added to Schedule I of the Single Convention on Narcotic Drugs of 1961.
Methoxyacetylfentanyl (2-methoxy-N-phenyl-N-[1-(2-phenylethyl)piperidin-4- yl]acetamide) is a synthetic analogue of the opioid fentanyl. Samples obtained from seizures and from other sources suggest that methoxyacetylfentanyl is available in the form of powders, liquids and tablets.
WHO review history
Methoxyacetylfentanyl has not been previously pre-reviewed or critically reviewed by the WHO ECDD. A critical review was proposed based on information brought to WHO’s attention that methoxyacetylfentanyl poses a serious risk to public health and has no recognized therapeutic use.
Similarity to known substances and effects on the central nervous system
Methoxyacetylfentanyl has a higher affinity to μ-opioid receptors than to κ- and δ-opioid receptors and has been shown to act as an agonist at the μ-opioid receptor. In animals, it produces analgesia with a potency higher than that of morphine and close to that of fentanyl. The analgesia was blocked by the opioid antagonist naltrexone, confirming its opioid mechanism of action.
The most serious acute health risk is respiratory depression, which in the case of an overdose can lead to respiratory arrest and death. This is consistent with its opioid mechanism of action.
Dependence potential
There are no studies of the dependence potential of this substance in humans or laboratory animals. However, based on its mechanism of action, methoxyacetylfentanyl would be expected to produce dependence similar to other opioid drugs.
Actual abuse and/or evidence of likelihood of abuse
In the animal drug discrimination model of subjective drug effects, methoxyacetylfentanyl produced effects similar to those of morphine. It also decreased activity levels and both the discriminative and rate-decreasing effects were blocked by the opioid antagonist naltrexone. Based on its receptor action and these effects in animal models, it would be expected that methoxyacetylfentanyl would be subject to abuse in a manner comparable to that of other opioids.
There is evidence that methoxyacetylfentanyl has been administered by injection and by nasal insufflation of powder. A large number of seizures of this substance have been reported in Europe and the United States. A number of deaths have been reported in Europe and the United States following which methoxyacetylfentanyl was detected in postmortem samples. While other drugs were also present in most of these cases, methoxyacetylfentanyl was deemed the cause of death or a major contributor to death in a significant proportion of them. Several countries have placed methoxyacetylfentanyl under national control.
Therapeutic usefulness
Methoxyacetylfentanyl is not known to have any therapeutic use.
Recommendation
The Committee considered that methoxyacetylfentanyl is a substance with high abuse liability and dependence potential. It is an opioid agonist that is more potent than morphine and its use has contributed to a large number of deaths in different regions. It has no therapeutic use and it poses a significant risk to public health. The Committee considered that the evidence of its abuse warrants placement under international control.
■■ Recommendation: The Committee recommended that methoxyacetylfentanyl (2-methoxy-N-phenyl-N-[1-(2-phenylethyl) piperidin-4-yl] acetamide) be added to Schedule I of the Single Convention on Narcotic Drugs of 1961.
ECDD Recommendation
Inclusion in Schedule I of the 1961 Convention on Narcotic Drugs
Link to full TRS
9789241210270-eng.pdf453.93 KB
MS Questionnaire Report