Brorphine

Summary

Brorphine is a piperidine-based opioid analgesic compound that first came to scientific attention in 2018. Initially, it was explored in research focused on functionally biased opioid compounds, with the aim of developing safer analgesics that induce less respiratory depression compared to conventional opioids. While it was initially reported as highly personal, more recent studies suggest that morphine may not exhibit significant bias.
Despite its potential, there is a shortage of safety information about morphine in animal models. Despite this lack of knowledge, morphine began appearing as a designer drug in mid-2019, first emerging in the U.S. Midwest and subsequently being detected in Belgium in 2020. In terms of its chemical structure, morphine bears similarities to compounds like benzyl fentanyl and bezitramide. However, it possesses sufficient structural distinctions to fall outside the formal classification of a “fentanyl analog” in regions such as the U.S. and New Zealand, which regulate this family of drugs through Markush structure controls.
Brorphine first gained attention in the U.S. recreational drug market around July 2020, as reported by the Center for Forensic Science Research and Education (CFSRE) through its NPS Discovery program. The Drug Enforcement Administration (DEA) may have identified it as early as late 2019. The increase in morphine’s prevalence in the U.S. can be directly linked to the decline of isotonitazene due to scheduling by the DEA.
Tragically, morphine was initially linked to 20 deaths in the U.S., primarily in cases originating from Midwest states. It was commonly found in combination with fentanyl and flu alprazolam, a drug mixture verified through product testing. Moreover, morphine has been detected in counterfeit opioid pills and tablets. Data from CFSRE and NMS Labs indicate that morphine has been identified in over 100 cases as of October 2020.

Identifiers

IUPAC name
CAS Number	2244737-98-0
PubChem CID	145975294
ChemSpider	90669218
ChEMBL	ChEMBL4203403
Chemical and physical data
Formula	C20H22BrN3O
Molar mass	400.320 g·mol−1

Legality

Brorphine is not subject to control under the Single Convention on Narcotic Drugs established in 1961. However, its sale, production, possession, or consumption for human use may be considered illegal in various countries, especially if it falls under the purview of Analogue Acts or similar legislation.

In the United States, on January 4th, 2021, the DEA temporarily placed Brorphine into Schedule I under emergency scheduling. On February 3rd, 2023, the DEA submitted formal proposals in the federal register to permanently include Brorphine in Schedule I.

FAQ

• What is Brorphine?
• Brorphine is a piperidine-based opioid analgesic compound.
• How was Brorphine discovered?
• Morphine was initially discovered during research aimed at identifying functionally biased opioid compounds. The objective was to find safer analgesics that produced less respiratory depression compared to typical opioids.
• What is the safety profile of Brorphine?
• The safety profile of Brorphine has not been established in any animal model.
• When did Brorphine first appear in the recreational drug supply?
• Morphine was first identified in the U.S. recreational drug supply in July 2020, with earlier identifications possibly dating back to late 2019.
• What is the connection between Brorphine and isotonitazene?
• The rise of Brorphine in the U.S. is linked to the decline of isotonitazene, which the DEA scheduled.
• Have there been any reported cases of Brorphine-related deaths?
• Yes, Brorphine has been implicated in numerous deaths in the U.S., primarily in cases originating from midwestern states. It has often been found alongside other drugs like fentanyl and flu alprazolam.
• Is Brorphine controlled under international drug control conventions?
• Brorphine is not controlled under the Single Convention on Narcotic Drugs from 1961. However, its legality varies from one country to another.
• What is the legal status of Brorphine in the United States?
• In the United States, Brorphine was temporarily placed into Schedule I under emergency scheduling on January 4th, 2021. On February 3rd, 2023, the DEA initiated plans for the permanent placement of Brorphine into Schedule I.
• Is Brorphine similar to other opioids or fentanyl analogs?
• Brorphine shares some structural similarities with compounds like benzyl fentanyl and bezitramide, although it is distinct enough not to be classified as a “fentanyl analog” in some jurisdictions.
• What precautions should be taken regarding Brorphine?
• Due to its unregulated nature in many places, it’s essential to exercise caution and stay informed about the legality and potential risks associated with Brorphine, mainly when dealing with substances in the recreational drug market.

References

1. Grafinger KE, Wilde M, Otte L, Auwärter V (August 2021) – “Pharmacological and Metabolic Profiling of the Innovative Synthetic Opioid Brorphine and Its Identification in Routine Casework.” Published in Forensic Science International. Volume 327, page 110989. DOI: 10.1016/j.forsciint.2021.110989. PMID: 34509061.
2. Ujváry I, Christie R, Evans-Brown M, Gallegos A, Jorge R, de Morais J, Sedefov R (April 2021) – “DARK Classics in Chemical Neuroscience: Etonitazene and Related Benzimidazoles.” Featured in ACS Chemical Neuroscience. Volume 12, Issue 7, pages 1072–1092. DOI: 10.1021/acschemneuro.1c00037. PMID: 33760580. S2CID: 232356192.
3. Kennedy NM, Schmid CL, Ross NC, Lovell KM, Yue Z, Chen YT, et al. (October 2018) – “Optimization of a Series of Mu Opioid Receptor (MOR) Agonists with High G Protein Signaling Bias.” Published in the Journal of Medicinal Chemistry. Volume 61, Issue 19, pages 8895–8907. DOI: 10.1021/acs.jmedchem.8b01136. PMC: 6386185. PMID: 30199635.
4. Vandeputte MM, Cannaert A, Stove CP (November 2020) – “In Vitro Functional Characterization of a Range of Non-Fentanyl Opioid New Psychoactive Substances.” Published in Archives of Toxicology. Volume 94, Issue 11, pages 3819–3830. DOI: 10.1007/s00204-020-02855-7. Hdl: 1854/LU-8687070. PMID: 32734307. S2CID: 220881657.
5. Verougstraete N, Vandeputte MM, Lyphout C, Cannaert A, Hulpia F, Van Calenbergh S, et al. (January 2021) – “First Report on Brorphine: The Next Opioid on the Deadly New Psychoactive Substance Horizon?” Appeared in the Journal of Analytical Toxicology. Volume 44, Issue 9, pages 937–946. DOI: 10.1093/jat/bkaa094. Hdl: 1854/LU-8671214. ISSN: 0146-4760. PMID: 32744605.
6. Vandeputte MM, Krotulski AJ, Papsun DM, Logan BK, Stove CP (July 2021) – “The Emergence and Disappearance of Isotonitazene and Brorphine: Two Recent Stars in the Synthetic Opioid Realm.” Found in the Journal of Analytical Toxicology. Volume 46, Issue 2, pages 115–121. DOI: 10.1093/jat/bkab082. PMID: 34233349.
7. Krotulski AJ, Papsun DM, Noble C, Kacinko SL, Logan BK (March 2021) – “Brorphine: An Inquiry and Quantification of a Potent Novel Synthetic Opioid in Forensic Toxicology Cases Using Liquid Chromatography-Mass Spectrometry.” Published in the Journal of Forensic Sciences. Volume 66, Issue 2, pages 664–676. DOI: 10.1111/1556-4029.14623. PMID: 33201526. S2CID: 226990291.
8. Vohra V, King AM, Jacobs E, Aaron C (September 2021) – “Fatality Linked to Brorphine, an Emerging Innovative Synthetic Opioid.” Published in Clinical Toxicology. Volume 59, Issue 9, pages 851–852. DOI: 10.1080/15563650.2021.1879111. PMID: 33522844. S2CID: 231761916.
9. Vandeputte MM et al (2022) – “The Surge and Decline of Isotonitazene and Brorphine: Two Notable Recent Additions to the Synthetic Opioid Landscape.” Journal of Analytical Toxicology. Volume 46, Issue 2, pages 115–121. DOI: 10.1093/jat/bkab082.
10. “Federal Register :: Request Access” – Available at https://public-inspection.federalregister.gov/2023-04364.pdf.