UNODC – August 2020: Brorphine (1-(1-(1-(4-bromophenyl)ethyl)piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one) is a recently emerging, highly potent synthetic opioid that has been seen in an increasing number of detections in seized drug samples and forensic casework since 2019, especially after isotonitazene was temporarily scheduled by the US Drug Enforcement Agency in June 2020.[1] Brorphine was first reported to the UNODC Early Warning Advisory on NPS in 2019. It is not under international control.
While the substance has some structural similarities with fentanyl, brorphine falls outside of the typical scope of generic legislations for fentanyl analogues.[2] Compounds belonging to this opioid sub-class were first established by Janssen Pharmaceuticals to be central nervous system depressants with morphine-like, analgesic activity.[3] Recent in vitro studies on brorphine found that it acts as a full mu-opioid receptor agonist which would likely result in opioid-like pharmacological effects and has a potency greater than morphine.[4] Brorphine users have reported similar opioid-like effects including euphoria and dependence, and the substance has been actively discussed and compared to other synthetic opioids on online forums.[5]
The substance has appeared as a grey granular powder similar to isotonitazene, and has been detected in seized drug samples and toxicology cases in Canada, United States, Sweden and Belgium since 2019.[6] Recently, between June to July 2020, the substance has been detected in 7 post-mortem cases in the United States alongside fentanyl, flualprazolam and heroin.[7]
More information on brorphine and other newly emerging synthetic opioids will be available in the upcoming Global SMART Update Vol. 24, September 2020.
Figure: Molecular structure of brorphine
Source: UNODC Early Warning Advisory
References:
[1] The Center for Forensic Science Research, The Rise of Brorphine — A Potent New Synthetic Opioid Identified in the Midwestern United States (July 2020).
[2] Nick Verougstraete and others, “First report on brorphine: the next opioid on the deadly new psychoactive substances’ horizon?”, Journal of Analytical Toxicology (2020), Accepted Manuscript, bkaa094.
[3] Paul Adriaan Jan Janssen, “Derivatives of Benzimidazolinyl Piperidine”, Janssen Pharmaceutica N.V., United States Patent 3,318,900 (May 1967).
[4] Nicole M. Kennedy and others, “Optimization of a Series of Mu Opioid Receptor (MOR) Agonists with High G Protein Signaling Bias”, Journal of Medicinal Chemistry, vol. 61 (2018), no. 19, pp. 8895-8907; Nick Verougstraete and others, “First report on brorphine: the next opioid on the deadly new psychoactive substances’ horizon?”, Journal of Analytical Toxicology (2020), Accepted Manuscript, bkaa094.
[5] Nick Verougstraete and others, “First report on brorphine: the next opioid on the deadly new psychoactive substances’ horizon?”, Journal of Analytical Toxicology (2020), Accepted Manuscript, bkaa094; United States, Drug Enforcement Administration, Diversion Control Division, Drug & Chemical Evaluation Section, Brorphine (chemical name:1-(1-(1-(4-bromophenyl)ethyl)piperidin-4-yl)-1,3-dihydro-2H-benzimidazol-2-one) (August 2020).
[6] UNODC, Early Warning Advisory on NPS, 2019 – 2020; The Center for Forensic Science Research, The Rise of Brorphine — A Potent New Synthetic Opioid Identified in the Midwestern United States (July 2020); European Monitoring Centre for Drugs and Drug Addiction, “EU Early Warning System Situation Report: Situation report 1 – June 2020”, EU-EWS-SITREP-2020-0001 (Lisbon, Portugal, June 2020).
[7] The Center for Forensic Science Research, The Rise of Brorphine — A Potent New Synthetic Opioid Identified in the Midwestern United States (July 2020).
For more information, please see:
June 2020 – UNODC-SMART: Emergence of the new synthetic opioid isotonitazene
UNODC, “Understanding the global opioid crisis”, Global SMART Update Vol. 21 (2019).
UNODC, “Fentanyl and its analogues – 50 years on”, Global SMART Update Vol. 17 (2017).