U-47700, also known asU4,pink heroin,pinky, andpink, is anopioidanalgesic drug developed by a team atUpjohn in the 1970s[1] which has around 7.5 times the potency ofmorphine in animal models.[2][3][4]
U-47700 is a structural isomer of the earlier opioidAH-7921[6] and the result of a great deal of work elucidating thequantitative structure–activity relationship of the scaffold. Upjohn looked for the keymoieties which gave the greatest activity[7] and posted over a dozen patents on related compounds, each optimizing one moiety[8][9][10][11][12][13][14][15] until they discovered that U-47700 was the most active.[16]
U-47700 became the lead compound of selective kappa-opioid receptor ligands such asU-50488, U-51754 (containing apyrrolidine rather than adimethylamine substituent) andU-69,593, which share very similar structures.[17][18] Although not used medically, the selective kappa ligands are used in research.[19][20]
U-47700 is an agonist of theμ-opioid receptor (Ki11.1 ± 0.4 nM) and possesses significantly loweraffinity for theκ-opioid receptor (Ki =287 ± 24 nM) andδ-opioid receptor (Ki =1220 ± 82 nM). U-47700 is approximately 10-fold more potent than morphine in rats, although the binding of U-47700 is 2–4 times weaker than morphine at all three opioid receptors.[21]
The metabolism of U-47700 in humans involves mono- and didesmethylation followed by hydroxylation.[22] The desmethyl metabolites of U-47700 have negligible affinity for the opioid receptors and are not thought to contribute to the activity of U-47700.[23][24]
Combined consumption of U-47700 withfentanyl andflubromazepam caused one fatality each in Belgium and Germany, respectively.[34][35][36] One death was reported in Ireland[37] and another one in Italy.[38] 17 opioid overdoses and several deaths in the United States had initially been associated with U-47700 in April 2016.[39] As of September 2016 at least 15 fatalities were confirmed. By December 2017, at least 46 fatalities had been associated with the use of U-47700.[40][41][42][43][44][45][46]
U-47700 was found in combination with fentanyl during the autopsy of the American artistPrince in 2016.[47]
U-47700 may be measured inserum,plasma, blood or urine to monitor for abuse, confirm a diagnosis of poisoning, or assist in a medicolegal death investigation. Serum or blood U-47700 concentrations are expected to be in a range of 10–250μg/L in intoxicated patients and 100–1,500 μg/L in deceased victims of acute overdosage. The detection usually involves analysis byliquid chromatography-mass spectrometry.[48]
U-47700 was emergency scheduled in Florida on September 27, 2016, by an emergency rule of Florida Attorney General Pam Bondi.[52]
Responding to a perceived threat to public health and safety, the U.S. Drug Enforcement Administration has placed U-47700 into Schedule I of the Controlled Substances Act, effective November 14, 2016.[53] In April 2018, U-47700 was placed into Schedule I indefinitely.[54]
U-47700 was placed into Schedule 1 of South Dakota's Controlled Substance Schedule. It was signed by GovernorDaugaard on February 9, 2017.[55]
U-47700 was made a Class A, Schedule 1 drug under the Misuse of Drugs Act in the UK in 2017.[56]
U-47700 is the title of a 2021Dutchsci-fi short film by directorErasmo de la Parra.[57] In the film, the characters are addicted to a new drug containing the substance U-47700.
^Cheney BV, Szmuszkovicz J, Lahti RA, Zichi DA (December 1985). "Factors affecting binding of trans-N-[2-(methylamino)cyclohexyl]benzamides at the primary morphine receptor".Journal of Medicinal Chemistry.28 (12):1853–1864.doi:10.1021/jm00150a017.PMID2999404.
^Harper NJ, Veitch GB, Wibberley DG (November 1974). "1-(3,4-Dichlorobenzamidomethyl)cyclohexyldimethylamine and related compounds as potential analgesics".Journal of Medicinal Chemistry.17 (11):1188–1193.doi:10.1021/jm00257a012.PMID4416926.
^Szmuszkovicz J, Von Voigtlander PF (October 1982). "Benzeneacetamide amines: structurally novel non-m mu opioids".Journal of Medicinal Chemistry.25 (10):1125–1126.doi:10.1021/jm00352a005.PMID6128415.
^Tsibulnikov SY, Maslov LN, Mukhomedzyanov AV, Krylatov AV, Tsibulnikova MR, Lishmanov YB (October 2015). "Prospects of Using of κ-Opioid Receptor Agonists U-50,488 and ICI 199,441 for Improving Heart Resistance to Ischemia/Reperfusion".Bulletin of Experimental Biology and Medicine.159 (6):718–721.doi:10.1007/s10517-015-3057-8.PMID26519268.S2CID1046853.
^Jones MJ, Hernandez BS, Janis GC, Stellpflug SJ (January 2017). "A case of U-47700 overdose with laboratory confirmation and metabolite identification".Clinical Toxicology.55 (1):55–59.doi:10.1080/15563650.2016.1209767.PMID27549165.S2CID27920117.
^Domanski K, Kleinschmidt KC, Schulte JM, Fleming S, Frazee C, Menendez A, Tavakoli K (January 2017). "Two cases of intoxication with new synthetic opioid, U-47700".Clinical Toxicology.55 (1):46–50.doi:10.1080/15563650.2016.1209763.PMID27432224.S2CID46228909.
^Armenian P, Olson A, Anaya A, Kurtz A, Ruegner R, Gerona RR (January 2017). "Fentanyl and a Novel Synthetic Opioid U-47700 Masquerading as Street "Norco" in Central California: A Case Report".Annals of Emergency Medicine.69 (1):87–90.doi:10.1016/j.annemergmed.2016.06.014.PMID27473610.
^abRambaran KA, Fleming SW, An J, Burkhart S, Furmaga J, Kleinschmidt KC, et al. (October 2017). "U-47700: A Clinical Review of the Literature".The Journal of Emergency Medicine.53 (4):509–519.doi:10.1016/j.jemermed.2017.05.034.PMID28911989.
^Coopman V, Blanckaert P, Van Parys G, Van Calenbergh S, Cordonnier J (September 2016). "A case of acute intoxication due to combined use of fentanyl and 3,4-dichloro-N-[2-(dimethylamino)cyclohexyl]-N-methylbenzamide (U-47700)".Forensic Science International.266:68–72.doi:10.1016/j.forsciint.2016.05.001.hdl:1854/LU-8509152.PMID27235591.
^Koch K, Auwärter V, Hermanns-Clausen M, Wilde M, Neukamm MA (April 2018). "Mixed intoxication by the synthetic opioid U-47700 and the benzodiazepine flubromazepam with lethal outcome: Pharmacokinetic data".Drug Testing and Analysis.10 (8):1336–1341.doi:10.1002/dta.2391.PMID29637722.
^Moody MT, Diaz S, Shah P, Papsun D, Logan BK (September 2018). "Analysis of fentanyl analogs and novel synthetic opioids in blood, serum/plasma, and urine in forensic casework".Drug Testing and Analysis.10 (9):1358–1367.doi:10.1002/dta.2393.PMID29633785.S2CID4758125.
N
Y (what is this?) (verify)
