Brorphine

{{Short description|Chemical compound}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Drugbox | drug_name = Brorphine | type = | IUPAC_name = 3-{1-[1-(4-bromophenyl)ethyl]piperidin-4-yl}-1''H''-benzimidazol-2-one | image = Brorphine.svg | image_class = skin-invert-image | width = 250px | alt =  | caption = | tradename = | MedlinePlus = | licence_EU = | licence_US = | pregnancy_AU =  | pregnancy_US =  | pregnancy_category = | legal_AU =  | legal_BR = F1 | legal_CA =  | legal_DE =  | legal_NZ =  | legal_UK =  | legal_US = Schedule I | legal_EU = | legal_UN =  | routes_of_administration = | addiction_liability =  | bioavailability = | protein_bound = | metabolism = | elimination_half-life = | excretion =  | CAS_number_Ref = | CAS_number = 2244737-98-0 | ChEMBL = 4203403 | ATC_prefix = | ATC_suffix = | PubChem = 145975294 | DrugBank = | KEGG = C22777 | ChemSpiderID = 90669218 | UNII_Ref = {{fdacite|correct|FDA}} | UNII =  | C = 20 | H = 22 | Br = 1 | N = 3 | O = 1 | melting_point = | smiles = CC(C1=CC=C(C=C1)Br)N2CCC(CC2)N3C4=CC=CC=C4NC3=O | StdInChI = 1S/C20H22BrN3O/c1-14(15-6-8-16(21)9-7-15)23-12-10-17(11-13-23)24-19-5-3-2-4-18(19)22-20(24)25/h2-9,14,17H,10-13H2,1H3,(H,22,25) | StdInChIKey = CNOFBGYRMCBVLO-UHFFFAOYSA-N }}

'''Brorphine''' is a piperidine-based opioid analgesic compound.<ref>{{cite journal | vauthors = Grafinger KE, Wilde M, Otte L, Auwärter V | title = Pharmacological and metabolic characterization of the novel synthetic opioid brorphine and its detection in routine casework | journal = Forensic Science International | volume = 327 | date = October 2021 | pmid = 34509061 | doi = 10.1016/j.forsciint.2021.110989 | article-number = 110989 }}</ref><ref>{{cite journal | vauthors = Ujváry I, Christie R, Evans-Brown M, Gallegos A, Jorge R, de Morais J, Sedefov R | title = DARK Classics in Chemical Neuroscience: Etonitazene and Related Benzimidazoles | journal = ACS Chemical Neuroscience | volume = 12 | issue = 7 | pages = 1072–1092 | date = April 2021 | pmid = 33760580 | doi = 10.1021/acschemneuro.1c00037 | s2cid = 232356192 }}</ref> Brorphine was originally discovered in a 2018 paper investigating functionally biased opioid compounds, with the intention of finding safer analgesics that produce less respiratory depression than typical opioids.<ref name="Kennedy_2018">{{cite journal | vauthors = Kennedy NM, Schmid CL, Ross NC, Lovell KM, Yue Z, Chen YT, Cameron MD, Bohn LM, Bannister TD | title = Optimization of a Series of Mu Opioid Receptor (MOR) Agonists with High G Protein Signaling Bias | journal = Journal of Medicinal Chemistry | volume = 61 | issue = 19 | pages = 8895–8907 | date = October 2018 | pmid = 30199635 | pmc = 6386185 | doi = 10.1021/acs.jmedchem.8b01136 }}</ref> Brorphine was originally reported to be highly biased, with an EC<sub>50</sub> of 4.8nM for GTPγS binding and 182nM for β-arrestin recruitment,<ref name="Kennedy_2018" /> however a more recent study found no significant bias for any of the compounds tested, including brorphine.<ref name="Vandeputte_2020" /> Its safety profile in any animal model has never been established.

Despite the lack of safety information on the compound, brorphine has been sold as a designer drug since mid-2019, initially being identified in the US Midwest, though it has since been found in 2020 in Belgium. It is related in chemical structure to compounds such as benzylfentanyl and bezitramide, though it is sufficiently structurally distinct to fall outside the formal definition of a "fentanyl analogue" in jurisdictions such as the US and New Zealand which have Markush structure controls over this family of drugs.<ref name="Vandeputte_2020">{{cite journal | vauthors = Vandeputte MM, Cannaert A, Stove CP | title = In vitro functional characterization of a panel of non-fentanyl opioid new psychoactive substances | journal = Archives of Toxicology | volume = 94 | issue = 11 | pages = 3819–3830 | date = November 2020 | pmid = 32734307 | doi = 10.1007/s00204-020-02855-7 | hdl-access = free | s2cid = 220881657 | bibcode = 2020ArTox..94.3819V | hdl = 1854/LU-8687070 }}</ref><ref>{{cite journal | vauthors = Verougstraete N, Vandeputte MM, Lyphout C, Cannaert A, Hulpia F, Van Calenbergh S, Verstraete AG, Stove C | title = First Report on Brorphine: The Next Opioid on the Deadly New Psychoactive Substance Horizon? | journal = Journal of Analytical Toxicology | volume = 44 | issue = 9 | pages = 937–946 | date = January 2021 | pmid = 32744605 | doi = 10.1093/jat/bkaa094 | hdl-access = free | hdl = 1854/LU-8671214 }}</ref> Despite its name, it is not a structural analog of morphine.

Brorphine was first identified in the U.S. recreational drug supply in July 2020 by the Center for Forensic Science Research and Education (CFSRE) through its NPS Discovery program; however, earlier identifications by the Drug Enforcement Administration (DEA) may have come as early as late 2019. The rise of brorphine in the U.S. can be directly linked to the decline of isotonitazene due to scheduling by the DEA.<ref>{{cite journal | vauthors = Vandeputte MM, Krotulski AJ, Papsun DM, Logan BK, Stove CP | title = The Rise and Fall of Isotonitazene and Brorphine: Two Recent Stars in the Synthetic Opioid Firmament | journal = Journal of Analytical Toxicology | volume = 46 | issue = 2 | pages = 115–121 | date = July 2021 | pmid = 34233349 | doi = 10.1093/jat/bkab082 | doi-access = free }}</ref> Brorphine was first implicated in 20 deaths in the U.S., primarily in cases originating from midwest states. Brorphine was commonly found with fentanyl and flualprazolam, a drug combination verified by drug product testing. Brorphine has also been identified in counterfeit opioid pills and tablets. Recently data from CFSRE and NMS Labs show that brorphine has been detected in more than 100 cases as of October 2020.<ref>{{cite journal | vauthors = Krotulski AJ, Papsun DM, Noble C, Kacinko SL, Logan BK | title = Brorphine-Investigation and quantitation of a new potent synthetic opioid in forensic toxicology casework using liquid chromatography-mass spectrometry | journal = Journal of Forensic Sciences | volume = 66 | issue = 2 | pages = 664–676 | date = March 2021 | pmid = 33201526 | doi = 10.1111/1556-4029.14623 | s2cid = 226990291 }}</ref><ref>{{cite journal | vauthors = Vohra V, King AM, Jacobs E, Aaron C | title = Death associated with brorphine, an emerging novel synthetic opioid | journal = Clinical Toxicology | volume = 59 | issue = 9 | pages = 851–852 | date = September 2021 | pmid = 33522844 | doi = 10.1080/15563650.2021.1879111 | s2cid = 231761916 }}</ref><ref>{{cite journal | vauthors = Vandeputte MM, Krotulski AJ, Papsun DM, Logan BK, Stove CP | title = The Rise and Fall of Isotonitazene and Brorphine: Two Recent Stars in the Synthetic Opioid Firmament | journal = Journal of Analytical Toxicology | volume = 46 | issue = 2 | pages = 115–121 | date = July 2021 | pmid = 34233349 | doi = 10.1093/jat/bkab082 }}</ref>

== Legality == Brorphine is not controlled under the Single Convention on Narcotic Drugs, 1961, or under the Federal Analogue Act, but it could be illegal to sell, produce, possess or consume it in several countries if it is sold for human consumption. In the United States, brorphine was placed into temporary emergency Schedule I for 2 years by the DEA on January 4, 2021.<ref>{{cite web | title = Schedules of Controlled Substances: Temporary Placement of Brorphine in Schedule I | work = Federal Register :: Request Access | date = 3 December 2020 | url = https://www.federalregister.gov/documents/2020/12/03/2020-26301/schedules-of-controlled-substances-temporary-placement-of-brorphine-in-schedule-i }}</ref> On February 3, 2023, the DEA filed plans in the Federal Register for permanent placement of brorphine into Schedule I.<ref>{{cite web | title = Schedules of Controlled Substances: Placement of Brorphine in Schedule I | work = Federal Register :: Request Access | date = 6 March 2023 | url = https://www.federalregister.gov/public-inspection/2023-04364/schedules-of-controlled-substances-placement-of-brorphine-in-schedule-i }}</ref><ref>{{cite web | title = Schedules of Controlled Substances: Placement of Brorphine in Schedule I: Final order | date = 6 March 2023 | publisher = U.S. Drug Enforcement Administration | url = https://public-inspection.federalregister.gov/2023-04364.pdf }}</ref>

== References == {{reflist}}

Category:Designer drugs Category:Opioids Category:Benzimidazoles Category:Benzimidazole opioids