Year(s) and type of review / ECDD meetings
Drug Class
Technical information (most recent pre-review / critical review report)
ECDD Recommendation
Inclusion in Schedule I of the 1961 Convention on Narcotic Drugs
Recommendation (from TRS)

Substance identification
Crotonylfentanyl (E-N-(1-phenylethylpiperidin-4-yl)-N-phenylbut-2-enamide) is a synthetic analogue of the opioid fentanyl and a structural isomer of cyclopropylfentanyl, both of which are controlled under Schedule I of the 1961 Single Convention on Narcotic Drugs. It is found in powder and tablet forms.

WHO review history
Crotonylfentanyl has not been reviewed previously. A critical review was proposed on the basis of information brought to WHO’s attention that crotonylfentanyl is manufactured clandestinely, poses a risk to public health and society and has no therapeutic use recognized by any Party.

Similarity to known substances and effects on the central nervous system
Crotonylfentanyl is a µ-opioid receptor agonist that is more potent than oxycodone and morphine but less potent than fentanyl. In view of its mechanism of action, it would be expected to produce the typical range of opioid effects, including analgesia, respiratory depression and sedation. In animals, it produces antinociceptive effects, which are blocked by the opioid antagonist naltrexone, and changes in locomotor activity.

Consistent with its µ-opioid agonist effect, the effects of crotonylfentanyl were reversed by an opioid antagonist in a clinical case of intoxication.

Dependence potential
No controlled experiments of the dependence potential of crotonylfentanyl were available. In view of its mechanism of action, however, crotonylfentanyl would be expected to produce dependence similar to other opioid drugs.

Actual abuse and/or evidence of likelihood of abuse
In drug discrimination assays in animals predictive of subjective effects in humans, crotonylfentanyl fully substituted for oxycodone and would therefore be likely to be abused.

In humans, the abuse potential of crotonylfentanyl has not been evaluated; however, the drug has been found in seized materials either alone or in combination with cyclopropylfentanyl.

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

The available evidence indicates that crotonylfentanyl has opioid actions and effects that are similar to those of other opioid agonists such as cyclopropylfentanyl and fentanyl, which are controlled under Schedule I of the 1961 Single Convention on Narcotic Drugs. Crotonylfentanyl has no known therapeutic use and could cause substantial harm.

■ Recommendation: The Committee recommended that crotonylfentanyl (E-N-(1-phenylethylpiperidin-4-yl)-N-phenylbut- 2-enamide) be added to Schedule I of the 1961 Single Convention on Narcotic Drugs.