Acetylfentanyl

IUPAC Name

N-[1-(2-phenylethyl)-4-piperidyl]-N-phenylacetamide

Year(s) and type of review / ECDD meetings
Drug Class
ECDD Recommendation
Inclusion in Schedule IV of the 1961 Convention on Narcotic Drugs
Recommendation (from TRS)
Substance identification
Chemically, acetylfentanyl is N-phenyl-N-[1-(2-phenylethyl)-4-piperidinyl] acetamide. It is in the phenylpiperidine class of synthetic opioids that includes fentanyl, a Schedule I drug under the UN 1961 Single Convention on Narcotic Drugs. Acetylfentanyl has also been referred to as "desmethyl fentanyl".

Previous review
Acetylfentanyl has not been previously reviewed by the Committee. A critical review was proposed based on information brought to WHO’s attention that acetylfentanyl is clandestinely manufactured, poses a risk to public health and society, and has no recognized therapeutic use by any Party.

Similarity to known substances and effects on the central nervous system
Acetylfentanyl displaces 3H-etorphine binding in rat cerebral membrane and can completely inhibit the mouse vas deferens stimulated twitch, which is reduced to 29.3 (±2.1)% levels by the µ-opioid receptor antagonist, beta-funaltrexamine, and reversed by an equimolar concentration of naltrexone. Overall, these data indicate that acetylfentanyl is a µ-opioid receptor agonist similar to morphine. Also similar to morphine-like µ-opioid receptor agonists, it has antinociceptive effects in several rodent models.

Dependence potential
Studies on physical dependence in animals have found that acetylfentanyl can relieve signs of withdrawal in morphine-dependent rhesus monkeys and thus demonstrates cross-dependency to morphine. There have been no published reports involving human subjects and acetylfentanyl under controlled conditions on the primary physical dependence-inducing effects, or the cross-dependency effects of acetylfentanyl.

Actual abuse and/or evidence of likelihood of abuse
Published reports involving controlled studies with acetylfentanyl in directly relevant abuse-liability procedures such as self-administration, drug discrimination, intra-cranial self-stimulation, or conditioned place preference are not currently available. Acetylfentanyl is being used for non-medical purposes, although the incidence and prevalence of its abuse cannot be accurately estimated partly because it is not routinely tested for in forensic toxicology. It has been identified in confiscated material being trafficked illicitly in the United States, Europe and Japan where it has been found as a white or pale-beige powder, in tablets and in nasal sprays, and in one report on blotting paper. At least eight countries have brought acetylfentanyl under some level of control as an abused substance. Users have reported using acetylfentanyl via insufflation, smoking, and through the intravenous routes of administration. It is sold over the Internet where it is sometimes promoted as a "research chemical", and its use is discussed on drug-user websites. Preclinical studies indicate that there is a narrow margin of safety for acetylfentanyl. More than 50 fatal intoxications involving acetylfentanyl have been reported from the United States, across Europe and from Japan.

Therapeutic usefulness
There are no known approved medical products containing acetylfentanyl, nor are there any known industrial uses for the drug.

Recommendation
Acetylfentanyl has effects similar to those of morphine and fentanyl that are included in Schedule I of the 1961 Single Convention on Narcotic Drugs. It has no recorded therapeutic use and its use has resulted in fatalities. Thus, because it meets the required condition of similarity, it is recommended that acetylfentanyl be placed in Schedule I of the Single Convention on Narcotic Drugs, 1961, as consistent with Article 3, paragraph 3 (iii) of that convention in that the substance is liable to similar abuse and productive of similar ill-effects to drugs in Schedule I. In addition, in accordance with Article 3, paragraph 5 of that convention, considering acetylfentanyl is particularly liable to abuse and to produce ill-effects, and its liability is not offset by substantial therapeutic advantages not possessed by substances other than drugs in Schedule IV, it is further recommended it be included in Schedule IV of the Single Convention on Narcotic Drugs, 1961.