Butyrfentanyl

Butyrfentanyl
Clinical data
ATC code	none;
Legal status
Legal status	BR: Class F1 (Prohibited narcotics); CA: Schedule I; DE: Anlage II (Authorized trade only, not prescriptible); 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;
KEGG	C22760;
CompTox Dashboard (EPA)	DTXSID30347410 ;
Chemical and physical data
Formula	C23H30N2O
Molar mass	350.506 g·mol−1
3D model (JSmol)	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;
	(verify)

Butyrfentanyl or butyrylfentanyl is a potent short-acting synthetic opioid analgesic drug. It is an analog of fentanyl with around one quarter of its potency. 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, μ-, δ-, κ-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 a designer drug.^[3]

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 K_i value for butyrfentanyl was 32 ± 4.1 nM. Comparing to fentanyl's K_i (1.06 ± 0.15 nM), butyrfentanyl's ability to displace [3H] fentanyl is low and it requires high concentrations of the drug.^[2]

Studies on urinary excretion revealed that almost all of the injected butyrfentanyl was excreted or metabolized within the first 3 hours after injection, and only very low concentrations were still detectable after 3 hours.^[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

There was a proposal being discussed by the UN Commission on Narcotic Drugs (CND) to include butyrfentanyl in Schedule 1 of the 1961 Single Convention on Narcotic Drugs which was passed 16 March 2017.^[5]

United Kingdom

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".

United States

As of May 2016, butyrfentanyl is a Schedule I controlled substance in the United States.^[6]

China

As of October 2015, butyrfentanyl is a controlled substance in China.^[7]

Switzerland

Butyrfentanyl is illegal in Switzerland as of December 2015.^[8]

References

^ "The College on Problem of Drug Dependence" (PDF). Archived from the original (PDF) on 19 December 2013., Foreword to the Drug Evaluation Committee (DEC) Analgesic, Stimulant, and Depressant Drug Indices
^ ^a ^b ^c ^d ^e Alburges ME (June 1988). Utilization of a radioreceptor assay for the analysis of fentanyl analogs in urine (PDF) (Ph.D. thesis). The University of Utah. Archived from the original (PDF) on 19 December 2013.
^ McIntyre IM, Trochta A, Gary RD, Wright J, Mena O (March 2016). "An Acute Butyr-Fentanyl Fatality: A Case Report with Postmortem Concentrations". Journal of Analytical Toxicology. 40 (2): 162–166. doi:10.1093/jat/bkv138. PMID 26683128.
^ Mounteney J, Giraudon I, Denissov G, Griffiths P (July 2015). "Fentanyls: Are we missing the signs? Highly potent and on the rise in Europe". The International Journal on Drug Policy. 26 (7): 626–631. doi:10.1016/j.drugpo.2015.04.003. PMID 25976511.
^ "Inclusion of butyrfentanyl in Schedule I of the Single Convention on Narcotic Drugs of 1961 as amended by the 1972 Protocol" (PDF).
^ "Schedules of Controlled Substances: Temporary Placement of Butyryl Fentanyl and Beta-Hydroxythiofentanyl into Schedule I" (PDF). Drug Enforcement Administration. 12 May 2016.
^ "关于印发《非药用类麻醉药品和精神药品列管办法》的通知" [Notice on Issuing the Measures for the Listing and Control of Non-Medicinal Narcotic Drugs and Psychotropic Substances] (in Chinese). China Food and Drug Administration. 27 September 2015. Archived from the original on 1 October 2015. Retrieved 1 October 2015.
^ "Verordnung des EDI über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien" [EDI regulation on the lists of narcotics, psychotropic substances, precursor substances and auxiliary chemicals] (in German). Der Bundesrat.