U-47700

U-47700, also known as pink heroin, pinky, and pink, is an opioid analgesic drug developed by a team at Upjohn in the 1970s[1] which has around 7.5 times the potency of morphine in animal models.[2][3][4]

Physical Sample of U-47700[5]
U-47700
Legal status
Legal status
  • AU: S9 (Prohibited substance)
  • CA: Schedule I
  • DE: Anlage II (Authorized trade only, not prescriptible)
  • UK: Class A
  • US: Schedule I
  • In general Unscheduled, Illegal in Finland, China and Sweden
Identifiers
IUPAC name
  • 3,4-Dichloro-N-[(1R,2R)-2-(dimethylamino)cyclohexyl]-N-methylbenzamide
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
Chemical and physical data
FormulaC16H22Cl2N2O
Molar mass329.27 g·mol−1
3D model (JSmol)
SMILES
  • ClC1=C(C=CC(=C1)C(=O)N(C)[C@@H]2CCCC[C@H]2N(C)C)Cl
InChI
  • InChI=1S/C16H22Cl2N2O/c1-19(2)14-6-4-5-7-15(14)20(3)16(21)11-8-9-12(17)13(18)10-11/h8-10,14-15H,4-7H2,1-3H3/t14-,15-/m1/s1
  • Key:JGPNMZWFVRQNGU-HUUCEWRRSA-N
 NY (what is this?)  (verify)

U-47700 is a structural isomer of the earlier opioid AH-7921[6] and the result of a great deal of work elucidating the quantitative structure–activity relationship of the scaffold. Upjohn looked for the key moieties 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 as U-50488, U-51754 (containing a pyrrolidine rather than a dimethylamine substituent) and U-69,593, which share very similar structures.[17][18] Although not used medically, the selective kappa ligands are used in research.[19][20]

Side effects

U-47700 has never been studied on humans, but would be expected to produce effects similar to those of other potent opioid agonists, including strong analgesia, sedation, euphoria, constipation, itching and respiratory depression which could be harmful or fatal.[21][22][23][24][25][26][27][28] Tachycardia was another side effect encountered with U-47700 use.[28] Tolerance and dependence would be expected to develop.[29]

Deaths

Combined consumption of U-47700 with fentanyl and flubromazepam caused one fatality in Belgium and Germany, respectively.[30][31][32] One death was reported in Ireland,[33] another one in Italy.[34] 17 opioid overdoses and several deaths in the United States had initially been associated with U-47700 in April 2016,[35] 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.[36][37][38][39][40][41][42]

U-47700 was found in combination with fentanyl during the autopsy of the American artist Prince in 2016.[43]

Detection in biological fluids

U-47700 may be measured in serum, 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 10–250 μg/L in intoxicated patients and 100–1,500 μg/L in deceased victims of acute overdosage. The detection usually involves analysis by liquid chromatography-mass spectrometry.[44]

Society and culture

Common street names for U-47700 include pinky, pink, and U4.[45]

Following its sale as a designer drug, U-47700 was made illegal in Sweden on January 26, 2016.[46]

U-47700 was emergency scheduled in Ohio on May 3, 2016 by executive order of Governor John Kasich.[47]

U-47700 was emergency scheduled in Florida on September 27, 2016 by an emergency rule of Florida Attorney General Pam Bondi.[48]

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.[49] In April 2018, U-47700 was placed into Schedule I indefinitely.[50]

U-47700 was placed into Schedule 1 of South Dakota's Controlled Substance Schedule. It was signed by Governor Daugaard on February 9, 2017.[51]

U-47700 is the title of a 2021 Dutch sci-fi short film by director Erasmo de la Parra.[52] In the film, the characters are addicted to a new drug containing the substance U-47700.

See also

References

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  2. 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): 1853–64. doi:10.1021/jm00150a017. PMID 2999404.
  3. 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): 1188–93. doi:10.1021/jm00257a012. PMID 4416926.
  4. Szmuszkovicz J, Von Voigtlander PF (October 1982). "Benzeneacetamide amines: structurally novel non-m mu opioids". Journal of Medicinal Chemistry. 25 (10): 1125–6. doi:10.1021/jm00352a005. PMID 6128415.
  5. Alzghari SK, Fleming SW, Rambaran KA, Long JE, Burkhart S, An J, Furmaga J (October 2017). "U-47700: An Emerging Threat". Cureus. 9 (10): e1791. doi:10.7759/cureus.1791. PMC 5741271. PMID 29282436.
  6. Brittain RT, Kellett DN, Neat ML, Stables R (September 1973). "Proceedings: Anti-nociceptive effects in N-substituted cyclohexylmethylbenzamides". British Journal of Pharmacology. 49 (1): 158P–159P. doi:10.1111/j.1476-5381.1973.tb08279.x. PMC 1776456. PMID 4207044.
  7. Michalson ET, Szmuszkovicz J (1989). Medicinal agents incorporating the 1,2-diamine functionality. Progress in Drug Research. Fortschritte der Arzneimittelforschung. Progrès des Recherches Pharmaceutiques. Progress in Drug Research. Vol. 33. Birkhäuser Basel. pp. 135–149. doi:10.1007/978-3-0348-9146-2_6. ISBN 9783034891462. PMID 2687936.
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  9. Harper NJ, Veitch GB (17 August 1976). "Patent US3975443 - 1-(3,4-dichlorobenzamidomethyl)-cyclohexyldimethylamine".
  10. Jacob Szmuszkovicz Kalamazoo (3 March 1970). "Patent US3499033 - Ethers of α-phenyl-2-aminocycloalkanemethanols".
  11. Jacob Szmuszkovicz (5 May 1970). "Patent US3510492 - 2-anilino and 2-anilinomethyl cycloalkylamines".
  12. Rynbrandt RH, Skaletzky LL (7 March 1972). "Patent US3647804 - Cycloalkanecarboxamides".
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  46. "31 nya ämnen kan klassas som narkotika eller hälsofarlig vara" (in Swedish). Folkhälsomyndigheten. November 2015.
  47. John R. Kasich (May 3, 2016). "Executive Order 2016-01K" (PDF). Governor of Ohio.
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  50. "Schedules of Controlled Substances: Placement of Butyryl Fentanyl and U-47700 Into Schedule I". Federal Register. 20 April 2018.
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