Utopioid (drug class) explained

Utopioids (U-type opioids) are a class of synthetic opioid analgesic drugs first developed in the 1970s by the pharmaceutical company Upjohn.^[1] However, they were never marketed for medical use. Some compounds from this class have been used for scientific research as model kappa opioid receptor agonists. In the mid-2010s, one mu opioid receptor selective compound from this class, U-47700, re-emerged as a designer drug and became widely sold around the world for several years before being banned in various jurisdictions from 2016 onwards. Following the prohibition of U-47700, a number of related compounds have continued to appear on illicit drug markets. They are often marketed online or included as components in mixtures sold under the guise of "street heroin." U-47700 itself is the most potent mu opioid agonist from this class, around 7-10x the potency of morphine. Some other compounds such as 3,4-MDO-U-47700 and N-Ethyl-U-47700 retain similar mu selectivity but with lower potency similar to that of morphine, or have a mixture of mu and kappa mediated effects, such as U-48800. Most utopioid derivatives are however selective kappa agonists, which may have limited abuse potential as dissociative hallucinogens, but do not alleviate withdrawal distress in opioid dependent individuals or maintain addiction in a typical sense. Nevertheless, this has not stopped them from being sold as designer drugs, and a number of these compounds are now banned in many jurisdictions alongside U-47700 itself.^{[2] [3] [4] [5] [6] [7] [8] [9]}

Table of Utopioids

Chemical structure	Drug name	PubChem	CAS number
	U-47109	44269286	67579-13-9
	U-47700	13544016	82657-23-6
	U-47931E (Bromadoline)	6328449	2418521-61-4
	U-48520	13544026	67579-11-7
	U-48800	137700072	2370977-17-4
	U-49900	129392412	67579-76-4
	U-50211 ^[10]	13544017	98587-47-4
	U-50488	3036289	67198-13-4
	U-51574	44269303
	U-62066 (Spiradoline)	55652	87151-85-7
	U-69593	105104	96744-75-1
	U-77891	117071705	119878-31-8
	N-Desmethyl-U-47700	129390993	67579-73-1
	N,N-Didesmethyl-U-47700	129406364	2616858-81-0
	3,4-MDO-U-47700	139598237	2488874-96-8
	3,4-Ethylenedioxy-U-47700	137700298	2749619-08-5
	3,4-Ethylenedioxy-U-51574	137700374	2748623-91-6
	N-Ethyl-U-47700	155907846
	N-Propyl-U-47700	137700434	2749433-76-7
	N-Isopropyl-U-47700	137700166	2748319-16-4
	N-Cyclopropyl-U-47700	165361451
	N-Methoxy-U-47700	155907659
	N-Methyl-U-47931E	54482637	75570-38-6
	3,4-Dibromo-U-47700
	3,4-Difluoro-U-47700	165362347	2417942-54-0
	2,4-Difluoro-U-48800
	4-TFM-U-48520 (U-04)	53720446	67579-38-8
	α-U10	165362154	2417942-61-9
	β-U10	54524276	67579-80-0

See also

• List of benzimidazole opioids
• List of fentanyl analogues

Notes and References

1. Web site: Utopioids . Cayman Chemical News and Announcements . 12 July 2018 .
2. Armenian P, Vo KT, Barr-Walker J, Lynch KL . Fentanyl, fentanyl analogs and novel synthetic opioids: A comprehensive review . Neuropharmacology . 134 . Pt A . 121–132 . May 2018 . 29042317 . 10.1016/j.neuropharm.2017.10.016 . 21404877 .
3. Sharma KK, Hales TG, Rao VJ, NicDaeid N, McKenzie C . The search for the "next" euphoric non-fentanil novel synthetic opioids on the illicit drugs market: current status and horizon scanning . Forensic Toxicology . 37 . 1 . 1–16 . 2019 . 30636980 . 6314991 . 10.1007/s11419-018-0454-5 .
4. Kyei-Baffour K, Lindsley CW . DARK Classics in Chemical Neuroscience: U-47700 . ACS Chemical Neuroscience . 11 . 23 . 3928–3936 . December 2020 . 32639714 . 10.1021/acschemneuro.0c00330 . 220438986 .
5. Baumann MH, Tocco G, Papsun DM, Mohr AL, Fogarty MF, Krotulski AJ . U-47700 and Its Analogs: Non-Fentanyl Synthetic Opioids Impacting the Recreational Drug Market . Brain Sciences . 10 . 11 . November 2020 . 895 . 33238449 . 7700279 . 10.3390/brainsci10110895 . free .
6. Vandeputte MM, Persson M, Walther D, Vikingsson S, Kronstrand R, Baumann MH, Gréen H, Stove CP . Characterization of recent non-fentanyl synthetic opioids via three different in vitro µ-opioid receptor activation assays . Archives of Toxicology . 96 . 3 . 877–897 . March 2022 . 35072756 . 10.1007/s00204-021-03207-9 . 246239574 .
7. Otte L, Wilde M, Auwärter V, Grafinger KE . Investigation of the μ- and κ-opioid receptor activation by eight new synthetic opioids using the [35 S]-GTPγS assay: U-47700, isopropyl U-47700, U-49900, U-47931E, N-methyl U-47931E, U-51754, U-48520, and U-48800 . Drug Testing and Analysis . 14 . 7 . 1187–1199 . July 2022 . 35142070 . 10.1002/dta.3238 . 246701889 . free .
8. Web site: Non-fentanyl opioids and related new psychoactive substances with no known legitimate uses. . International Narcotics Control Board . 28 January 2022 .
9. Vandeputte MM, Stove CP . In vitro μ-opioid receptor activation potential of U10 and β-U10, positional isomers of the synthetic opioid naphthyl U-47700 . Drug Testing and Analysis . 16. 3. 323–326. July 2023 . 37482925 . 10.1002/dta.3554 . 260101432 . free .
10. Cheney BV. Structure-activity relationships for drugs binding to the agonist and antagonist states of the primary morphine receptor. J Med Chem. 1988 Mar;31(3):521-31.