Para-methoxy-butyrylfentanyl

IUPAC Name

N-(2-fluorophenyl)-N-[1-(2-phenylethyl)-4-piperidinyl]-propanamide

Current Scheduling Status
None
Year(s) and type of review / ECDD meetings
Drug Class
ECDD Recommendation
Placed under surveillance
Recommendation (from TRS)
Substance identification
Para-methoxy-butyrylfentanyl (N-(4-methoxyphenyl)-N-[1-(2-phenylethyl) piperidin-4-yl]butanamide) is a synthetic analogue of the opioid analgesic fentanyl. Samples obtained from seizures and from other sources suggest that para-methoxy-butyrylfentanyl is available in the form of a powder, tablet and a nasal spray.

WHO review history
Para-methoxy-butyrylfentanyl 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 para-methoxy-butyrylfentanyl poses serious risk to public health and has no recognized therapeutic use.

Similarity to known substances and effects on the central nervous system
Para-methoxy-butyrylfentanyl has a higher affinity to μ-opioid receptors than to κ- and δ-opioid receptors and has been shown to act as a partial agonist at the μ-opioid receptor. In animals, it produces typical opioid effects including analgesia and, in some animal studies, it had a potency higher than that of morphine and close to that of fentanyl.

Reported clinical features of intoxication involving para-methoxy- butyrylfentanyl included the typical opioid effects of reduced level of consciousness, respiratory depression and pupil constriction. In some cases, treatment with the opioid antagonist naloxone was shown to reverse the drug-induced respiratory depression. While this is consistent with an opioid mechanism of action, it should be noted that in all such cases at least one other opioid was present.

Dependence potential
No studies of the dependence potential of this substance in humans or laboratory animals have been reported. However, based on its mechanism of action, para- methoxy-butyrylfentanyl would be expected to produce dependence similar to other opioid drugs.

Abuse potential and/or evidence of likelihood of abuse
No controlled studies of the abuse potential of para-methoxy-butyrylfentanyl have been reported and very little information is available on the extent of its abuse. Para-methoxy-butyrylfentanyl has been detected in biological samples obtained from a limited number of cases of acute intoxication. Reported clinical features are consistent with opioid effects, including respiratory depression. However, in all of the documented cases of severe adverse events associated with use of para- methoxy-butyrylfentanyl, other fentanyl analogues were also detected and the role of para-methoxy-butyrylfentanyl is therefore not clear.

Therapeutic usefulness
Para-methoxy-butyrylfentanyl is not known to have any therapeutic uses.

Recommendation
The limited information available indicates that para-methoxy-butyrylfentanyl is an analogue of the opioid analgesic fentanyl. There is evidence of its use in a limited number of countries, with few reports of intoxication and no reports of death. In the cases of intoxication, the role of para-methoxy-butyrylfentanyl was not clear owing to the presence of other opioids. It has no therapeutic use. Currently, there is little evidence that para-methoxy-butyrylfentanyl in causing substantial harm that would warrant its placement under international control.

■■ Recommendation: The Committee recommended that para-meth- oxy-butyrylfentanyl (N-(4-methoxyphenyl)-N-[1-(2-phenylethyl) piperidin-4-yl]butanamide) be kept under surveillance by the WHO Secretariat.