IUPAC Name
N-(4-fluorophenyl)-N-(1-phenethylpiperidin-4-yl)isobutyramide
Current Scheduling Status
Year(s) and type of review / ECDD meetings
Drug Class
Recommendation (from TRS)
Substance identification
Chemically, 4-fluoroisobutyrfentanyl (4-FIBF, pFIBF) is N-(4- Fluorophenyl)-2-methyl-N-[1-(2-phenylethyl)piperidin-4-yl]propanamide: 4-Fluoroisobutyryfentanyl is the positional isomer of 4-fluoro-butyrfentanyl (4- FIBF).
Previous review
4-Fluoroisobutyrfentanyl has not been previously pre-reviewed or critically reviewed. A direct critical review was proposed based on information brought to WHO’s attention that it is clandestinely manufactured, of especially serious risk to public health and society, and of no recognized therapeutic use by any Party. Preliminary information collected from various sources indicated that this substance may cause substantial harm and that it has no medical use.
Similarity to known substances and effects on the central nervous system
4-Fluoroisobutyryfentanyl is similar to fentanyl, a drug in Schedule I of the 1961 Single Convention on Narcotic Drugs. It is manufactured using precursors and synthetic methods similar to those used to manufacture the pharmaceutical, fentanyl.
4-Fluoroisobutyryfentanyl potently and preferentially binds to the µ-opioid receptor relative to the κ- and δ-opioid receptors. It also preferentially activates the µ-opioid receptor relative to the other opioid receptors. This in vitro profile is similar to that of fentanyl. Similar to fentanyl and morphine, 4-fluoroisobutyryfentanyl produces antinociception in laboratory animals that is blocked with naloxone. Consistent with clinical effects involving fentanyl analogues and derivatives, typical opioid overdose symptoms of central nervous system and respiratory depression, decreased consciousness and miotic pupils have been observed with 4-fluoroisobutyryfentanyl, but its use has also been associated with tachycardia and hypertension. Two countries have reported deaths associated with 4-fluoroisobutyryfentanyl use.
Dependence potential
No controlled, experimental studies of either laboratory animals or human subjects that are directly pertinent to the dependence potential of 4-fluoroisobutyryfentanyl are currently available.
Actual abuse and/or evidence of likelihood of abuse
Evidence of abuse of 4-Fluoroisobutyrfentanyl is available. It is currently sold online and through illicit markets as a nonscheduled substitute for illicit opioids and/or prescription opioids. It has been discussed on user forums where it is described as having typical opioid effects.
4-Fluoroisobutyryfentanyl has been encountered as a single substance, seized as a liquid, in powder form, and as tablets or in mixtures with heroin, fentanyl, furanyl fentanyl, metamfetamine and cocaine. Based on forensic reports and paraphernalia found at overdose sites, routes of administration appear to be intravenous, oral and as a nasal spray. 4-Fluoroisobutyryfentanyl has been connected to fatal overdoses in which intravenous and insufflation routes of administration were confirmed. One country reported that 62 overdose deaths involving 4-fluoroisobutyryfentanyl abuse had occurred in 2016 alone. Seizures of the compound have been reported from Europe and North America.
Therapeutic usefulness
No countries have approved 4-fluoroisobutryfentanyl for either medical or veterinary use.
Recommendation
4-Fluoroisobutyryfentanyl is an opioid that has similar in vitro and in vivo effects to those of fentanyl and other fentanyl analogues that are included in Schedule I of the 1961 Single Convention on Narcotic Drugs. It potently and preferentially binds to, and activates the µ-opioid receptor more than the κ- and δ-opioid receptors. Similar to fentanyl and morphine, 4-fluoroisobutyryfentanyl produces antinociception in laboratory animals, which is antagonized by naloxone. It is currently sold online and through illicit markets as a non-controlled substitute for illicit opioids and/or prescription opioids. Consistent with clinical effects involving fentanyl analogues and derivatives, typical opioid overdose symptoms of central nervous system and respiratory depression, decreased consciousness and miotic pupils have been observed with 4-fluoroisobutyryfentanyl.
4-Fluoroisobutyryfentanyl is a compound liable to similar abuse and with similar ill effects to controlled opioids such as fentanyl, which are included in Schedule I of the Single Convention on Narcotic Drugs of 1961. It has no recorded therapeutic use, and its use has been associated with fatalities. There is sufficient evidence that it is being or is likely to be abused so as to constitute a public health and social problem warranting the placing of the substance under international control. Thus, because it meets the required condition of similarity, it is recommended that 4-fluoroisobutyryfentanyl (N-(4-Fluorophenyl)-2- methyl-N-[1-(2-phenylethyl)piperidin-4-yl]propanamide) 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.
Chemically, 4-fluoroisobutyrfentanyl (4-FIBF, pFIBF) is N-(4- Fluorophenyl)-2-methyl-N-[1-(2-phenylethyl)piperidin-4-yl]propanamide: 4-Fluoroisobutyryfentanyl is the positional isomer of 4-fluoro-butyrfentanyl (4- FIBF).
Previous review
4-Fluoroisobutyrfentanyl has not been previously pre-reviewed or critically reviewed. A direct critical review was proposed based on information brought to WHO’s attention that it is clandestinely manufactured, of especially serious risk to public health and society, and of no recognized therapeutic use by any Party. Preliminary information collected from various sources indicated that this substance may cause substantial harm and that it has no medical use.
Similarity to known substances and effects on the central nervous system
4-Fluoroisobutyryfentanyl is similar to fentanyl, a drug in Schedule I of the 1961 Single Convention on Narcotic Drugs. It is manufactured using precursors and synthetic methods similar to those used to manufacture the pharmaceutical, fentanyl.
4-Fluoroisobutyryfentanyl potently and preferentially binds to the µ-opioid receptor relative to the κ- and δ-opioid receptors. It also preferentially activates the µ-opioid receptor relative to the other opioid receptors. This in vitro profile is similar to that of fentanyl. Similar to fentanyl and morphine, 4-fluoroisobutyryfentanyl produces antinociception in laboratory animals that is blocked with naloxone. Consistent with clinical effects involving fentanyl analogues and derivatives, typical opioid overdose symptoms of central nervous system and respiratory depression, decreased consciousness and miotic pupils have been observed with 4-fluoroisobutyryfentanyl, but its use has also been associated with tachycardia and hypertension. Two countries have reported deaths associated with 4-fluoroisobutyryfentanyl use.
Dependence potential
No controlled, experimental studies of either laboratory animals or human subjects that are directly pertinent to the dependence potential of 4-fluoroisobutyryfentanyl are currently available.
Actual abuse and/or evidence of likelihood of abuse
Evidence of abuse of 4-Fluoroisobutyrfentanyl is available. It is currently sold online and through illicit markets as a nonscheduled substitute for illicit opioids and/or prescription opioids. It has been discussed on user forums where it is described as having typical opioid effects.
4-Fluoroisobutyryfentanyl has been encountered as a single substance, seized as a liquid, in powder form, and as tablets or in mixtures with heroin, fentanyl, furanyl fentanyl, metamfetamine and cocaine. Based on forensic reports and paraphernalia found at overdose sites, routes of administration appear to be intravenous, oral and as a nasal spray. 4-Fluoroisobutyryfentanyl has been connected to fatal overdoses in which intravenous and insufflation routes of administration were confirmed. One country reported that 62 overdose deaths involving 4-fluoroisobutyryfentanyl abuse had occurred in 2016 alone. Seizures of the compound have been reported from Europe and North America.
Therapeutic usefulness
No countries have approved 4-fluoroisobutryfentanyl for either medical or veterinary use.
Recommendation
4-Fluoroisobutyryfentanyl is an opioid that has similar in vitro and in vivo effects to those of fentanyl and other fentanyl analogues that are included in Schedule I of the 1961 Single Convention on Narcotic Drugs. It potently and preferentially binds to, and activates the µ-opioid receptor more than the κ- and δ-opioid receptors. Similar to fentanyl and morphine, 4-fluoroisobutyryfentanyl produces antinociception in laboratory animals, which is antagonized by naloxone. It is currently sold online and through illicit markets as a non-controlled substitute for illicit opioids and/or prescription opioids. Consistent with clinical effects involving fentanyl analogues and derivatives, typical opioid overdose symptoms of central nervous system and respiratory depression, decreased consciousness and miotic pupils have been observed with 4-fluoroisobutyryfentanyl.
4-Fluoroisobutyryfentanyl is a compound liable to similar abuse and with similar ill effects to controlled opioids such as fentanyl, which are included in Schedule I of the Single Convention on Narcotic Drugs of 1961. It has no recorded therapeutic use, and its use has been associated with fatalities. There is sufficient evidence that it is being or is likely to be abused so as to constitute a public health and social problem warranting the placing of the substance under international control. Thus, because it meets the required condition of similarity, it is recommended that 4-fluoroisobutyryfentanyl (N-(4-Fluorophenyl)-2- methyl-N-[1-(2-phenylethyl)piperidin-4-yl]propanamide) 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.
ECDD Recommendation
Inclusion in Schedule I of the 1961 Convention on Narcotic Drugs
Link to full TRS
9789241210188-eng.pdf417.9 KB
MS Questionnaire Report
4.9_4-fibf_annex1.pdf370.06 KB