Butyrfentanyl

Butyrfentanyl

Clinical data
ATC code	none
Legal status
Legal status	CA: Schedule I UK: Class A US: Schedule I
Identifiers
IUPAC name N-(1-(2-phenylethyl)-4-piperidinyl)-N-phenylbutyramide
CAS Number	1169-70-6
PubChem (CID)	621174
ChemSpider	539764
UNII	07V1H7R6ZN
Chemical and physical data
Formula	C23H30N2O
Molar mass	350.5 g/mol
3D model (Jmol)	Interactive image
SMILES CCCC(=O)N(C2CCN(CCc1ccccc1)CC2)c3ccccc3
InChI InChI=1S/C23H30N2O/c1-2-9-23(26)25(21-12-7-4-8-13-21)22-15-18-24(19-16-22)17-14-20-10-5-3-6-11-20/h3-8,10-13,22H,2,9,14-19H2,1H3 Key:QQOMYEQLWQJRKK-UHFFFAOYSA-N
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Butyr-fentanyl or butyrylfentanyl (not to be confused with 3-methylfentanyl) is a potent short-acting synthetic opioid analgesic drug. It is an analogue of fentanyl with around one quarter the potency of fentanyl. One of the first mentions of this drug can be found in document written by The College on Problem of Drug Dependence, where it is mentioned as N-butyramide fentanyl analog.^[1] This document also states that the article describing its clinical effects (analgesic studies, m-, d-, k-Opioid receptor binding and in vitro measures of drug efficacy, antinociceptive and narcotic properties) was published in 1987. It is an agonist for the μ-opioid receptors.^[2]

Butyrfentanyl has no current legitimate clinical applications, however it is being sold as designer drug.^[3]

Butyrfentanyl is illegal in the United Kingdom as it is a modification of fentanyl "by replacement of the N-propionyl group by another acyl group".

Side effects of fentanyl analogs are similar to those of fentanyl itself, which include itching, nausea and potentially serious respiratory depression, which can be life-threatening. Fentanyl analogs have killed hundreds of people throughout Europe and the former Soviet republics since the most recent resurgence in use began in Estonia in the early 2000s, and novel derivatives continue to appear.^[4]

Pharmacokinetics

Butyrfentanyl binds to the opioid receptor. During the studies of in vitro inhibition of specific [3H] fentanyl binding to the opioid receptor, the order of analogues was: (±)-cis-3-methylfentanyl > fentanyl = alpha-methylfentanyl > butyrylfentanyl > benzylfentanyl.^[2] The studies in inhibition studies on binding affinity achieved the same order of analogues. It means that butyrfentantyl is a less potent opioid-agonist than fentanyl. On the other side, during in vitro studies of cross-reactivity with the fentanyl antibody between fentanyl and the fentanyl analogs examined, revealed order: fentanyl = butyrylfentanyl > (±)-cis-3-methylfentanyl > benzylfentanyl > alpha-methylfentanyl.^[2] High cross-reactivity may be the effect of the shape of the molecule - the shape of butyrfentanyl is closest to the original fentanyl molecule, which makes it easy to bind by fentanyl antibodies.

The opioid receptor affinity of fentanyl and its analogs was determined from their inhibitory potency in a binding assay with [3H] fentanyl as the radioligand. The Ki value for butyrfentanyl was Ki=32 ± 4.1 nM. Comparing to fentanyl's Ki (Ki=1.06 ± 0.15 nM), butyrfentanyl's ability to displace [3H] fentanyl is low and it requires high concentrations of the drug.^[2]

During behavioral studies there was no evidence of causing adverse effects which accompany fentanyl's use. Animals injected with 45μg/kg i.v. showed no behavioral responses in mice: straub tail, truncal and limbs rigidity, respiratory depression. These responses where observed in animals injected with 15 μg/kg fentanyl i.v.^[2]

Studies on urinary excretion revealed that almost all of the injected butyrfentanyl was excreted or metabolized within the first 3 h after injection, and only very low concentrations were still detectable after 3 h.^[2] Urinary concentrations of butyrylfentanyl from animals injected with 15 μg/kg and 45 μg/kg i.v. were measured by two techniques: radioreceptorassay and gas chromatography/mass spectrometry (GC/MS).

Legal Status

United States

As of May 2016 Butyrfentanyl is a Schedule I controlled substance in the United States.^[5]

China

As of October 2015 Butyrfentanyl is a controlled substance in China.^[6]

Switzerland

Butyrfentanyl is illegal in Switzerland as of December 2015.^[7]

See also

• 3-Methylbutyrfentanyl
• 4-Fluorobutyrfentanyl
• 4-Fluorofentanyl
• α-Methylfentanyl
• Acetylfentanyl
• Benzylfentanyl
• Furanylfentanyl
• List of Fentanyl analogues

References

1. The College on Problem of Drug Dependence, Foreword to the Drug Evaluation Committee (DEC) Analgesic, Stimulant, and Depressant Drug Indices
2. Utilization of a radioreceptor assay for the analysis of fentanyl analogs in urine Mario Enrique Alburges
3. Iain M. McIntyre; Amber Trochta; Ray D. Gary; Jennifer Wright; Othon Mena (December 2015). "An Acute Butyr-Fentanyl Fatality: A Case Report with Postmortem Concentrations". Journal of Analytical Toxicology. doi:10.1093/jat/bkv138.
4. Jane Mounteney; Isabelle Giraudon; Gleb Denissov; Paul Griffiths (July 2015). "Fentanyls: Are we missing the signs? Highly potent and on the rise in Europe.". The international journal of drug policy. 26 (7): 626–631. doi:10.1016/j.drugpo.2015.04.003. PMID 25976511.
5. "Schedules of Controlled Substances: Temporary Placement of Butyryl Fentanyl and Beta-Hydroxythiofentanyl into Schedule I" (PDF). Drug Enforcement Agency. 12 May 2016.
6. "关于印发《非药用类麻醉药品和精神药品列管办法》的通知" (in Chinese). China Food and Drug Administration. 27 September 2015. Retrieved 1 October 2015.
7. "Verordnung des EDI über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien". Der Bundesrat.

Further reading

• Higashikawa Y, Suzuki S (June 2008). "Studies on 1-(2-phenethyl)-4-(N-propionylanilino)piperidine (fentanyl) and its related compounds. VI. Structure-analgesic activity relationship for fentanyl, methyl-substituted fentanyls and other analogues". Forensic Toxicology. 26 (1): 1–5. doi:10.1007/s11419-007-0039-1.
• Alburges ME, Hanson GR, Gibb JW, Sakashita CO, Rollins DE (1992). "Fentanyl receptor assay. II. Utilization of a radioreceptor assay for the analysis of fentanyl analogs in urine". J Anal Toxicol. 16 (1): 36–41. doi:10.1093/jat/16.1.36. PMID 1322477.
• Woods J, Medzihradsky F, Smith C, Winger G, Gmerek D (1988). "Evaluation of new compounds for opioid activity: 1987 annual report". NIDA Res. Monogr. 81: 543–90. PMID 3136388.
• Aceto M, Bowman E, Harris L, May E (1988). "Dependence studies of new compounds in the rhesus monkey, rat, and mouse, 1987". NIDA Res. Monogr. 81: 485–542. PMID 3136386.
• Brine GA, Boldt KG, Huang PT, Sawyer DK, Carroll FI (2009). "Carbon-13 nuclear magnetic resonance spectra of fentanyl analogs". Journal of Heterocyclic Chemistry. 26 (3): 677–686. doi:10.1002/jhet.5570260329.