Butyrfentanyl

Butyrfentanyl

File:Butyrfentanyl.jpg
Identifiers
IUPAC name N-(1-(2-phenylethyl)-4-piperidinyl)-N-phenylbutyramide
CAS Number	1169-70-6
PubChem CID	621174
ChemSpider	539764 Y
CompTox Dashboard (EPA)	DTXSID30347410
Chemical and physical data
Formula	C23H30N2O
Molar mass	350.5 g/mol 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)

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 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. 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 at mu opioid receptors.

Butyrfentanyl has no current legitimate clinical applications, but anecdotal reports indicate it may occasionally be surfacing on the grey-market as a recreational drug. This compound is not currently scheduled in the USA, but most likely falls under the purview of the federal and many state analogue drug laws. Butyrfentanyl is illegal in the United Kingdom owing to its chemical similarity to fentanyl.

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. 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. 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.

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 respones in mice: straub tail, truncal and limbs rigidity, respiratory depression. These respones where observed in animals injected with 15 μg/kg fentanyl i.v.

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. 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).

Further reading

• Higashikawa Y, Suzuki S (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. {{cite journal}}: Unknown parameter |month= ignored (help)
• 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. PMID 1322477.{{cite journal}}: CS1 maint: multiple names: authors list (link)
• 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
• 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
• Brine GA, Boldt KG, Huang P-T, Sawyer DK, Carroll FI (2009). "Carbon-13 nuclear magnetic resonance spectra of fentanyl analogs". Journal of Heterocyclic Chemistry. 26 (3): 677. doi:10.1002/jhet.5570260329.{{cite journal}}: CS1 maint: multiple names: authors list (link)