IUPAC Name
opioid
Current Scheduling Status
Year(s) and type of review / ECDD meetings
Drug Class
Recommendation (from TRS)
Substance identification
The chemical structure of brorphine (IUPAC chemical name: 3- {1- [1- (4-bromophenyl) ethyl] piperidin-4-yl} -1H-benzimidazol-2-one) is similar to that of bezitramide, an opioid listed in Schedule I of the 1961 Convention. Brorphine free base has been described as a white or off-white solid and the hydrochloride salt as a neat solid, with seized samples described as white, yellowish, grey, purple or white powder or in crystal form. It is also found in tablets and capsules as falsified opioid medicines. It is reported to be used by oral, inhalation and intravenous (iv) routes of administration.
WHO review history
Brorphine has not been formally reviewed by WHO and is not currently under international control. Information was brought to WHO’s attention that this substance is manufactured clandestinely, poses a risk to public health and is of no recognized therapeutic use.
Similarity to known substances and effects on the central nervous system
Brorphine is a full agonist at the μ-opioid receptor (MOR), with greater potency than morphine and less potency than fentanyl. It has analgesic effects that are reversed by an opioid antagonist and, based on its mechanism of action, it would be expected to produce other typical opioid effects such as respiratory depression and sedation. Brorphine may be convertible to bezitramide, which is an opioid listed in Schedule I of the 1961 Single Convention on Narcotic Drugs.
Dependence potential
No controlled studies in animals or humans have examined the dependence potential of brorphine. As a potent µ-opioid agonist, it would be expected to produce dependence similar to other opioid substances. Unverified online reports describe tolerance and withdrawal after repeated brorphine use.
Actual abuse and/or evidence of likelihood of abuse
In an animal model for predicting abuse potential, brorphine had effects similar to those of morphine and fentanyl.
Deaths involving brorphine have been reported in several countries. Deaths commonly occur after use of brorphine in combination with other opioids or with benzodiazepines such as flualprazolam. Brorphine has been identified in falsified opioid medicines, suggesting that its use may sometimes be unintentional. Fatal and non-fatal intoxications due to brorphine share features with intoxications due to other opioids, such as pulmonary oedema. Brorphine has been detected with other substances in biological fluids in cases of driving under the influence of drugs (DUID).
Seizures have been reported in multiple countries and regions.
Therapeutic usefulness
Brorphine is not known to have any therapeutic use.
Recommendation
The mechanism of action of brorphine indicates that it is likely to have similar abuse potential and ill effects as opioids that are controlled under Schedule I of the 1961 Single Convention on Narcotic Drugs. Its use has been reported in a number of countries and has been associated with adverse effects, including death. It has no known therapeutic use and is likely to cause substantial harm.
Recommendation: The Committee recommended that brorphine (IUPAC chemical name: 3- {1- [1- (4-bromophenyl) ethyl] piperidin-4-yl} -1H-benzimidazol-2-one) be added to Schedule I of the 1961 Single Convention on Narcotic Drugs.
The chemical structure of brorphine (IUPAC chemical name: 3- {1- [1- (4-bromophenyl) ethyl] piperidin-4-yl} -1H-benzimidazol-2-one) is similar to that of bezitramide, an opioid listed in Schedule I of the 1961 Convention. Brorphine free base has been described as a white or off-white solid and the hydrochloride salt as a neat solid, with seized samples described as white, yellowish, grey, purple or white powder or in crystal form. It is also found in tablets and capsules as falsified opioid medicines. It is reported to be used by oral, inhalation and intravenous (iv) routes of administration.
WHO review history
Brorphine has not been formally reviewed by WHO and is not currently under international control. Information was brought to WHO’s attention that this substance is manufactured clandestinely, poses a risk to public health and is of no recognized therapeutic use.
Similarity to known substances and effects on the central nervous system
Brorphine is a full agonist at the μ-opioid receptor (MOR), with greater potency than morphine and less potency than fentanyl. It has analgesic effects that are reversed by an opioid antagonist and, based on its mechanism of action, it would be expected to produce other typical opioid effects such as respiratory depression and sedation. Brorphine may be convertible to bezitramide, which is an opioid listed in Schedule I of the 1961 Single Convention on Narcotic Drugs.
Dependence potential
No controlled studies in animals or humans have examined the dependence potential of brorphine. As a potent µ-opioid agonist, it would be expected to produce dependence similar to other opioid substances. Unverified online reports describe tolerance and withdrawal after repeated brorphine use.
Actual abuse and/or evidence of likelihood of abuse
In an animal model for predicting abuse potential, brorphine had effects similar to those of morphine and fentanyl.
Deaths involving brorphine have been reported in several countries. Deaths commonly occur after use of brorphine in combination with other opioids or with benzodiazepines such as flualprazolam. Brorphine has been identified in falsified opioid medicines, suggesting that its use may sometimes be unintentional. Fatal and non-fatal intoxications due to brorphine share features with intoxications due to other opioids, such as pulmonary oedema. Brorphine has been detected with other substances in biological fluids in cases of driving under the influence of drugs (DUID).
Seizures have been reported in multiple countries and regions.
Therapeutic usefulness
Brorphine is not known to have any therapeutic use.
Recommendation
The mechanism of action of brorphine indicates that it is likely to have similar abuse potential and ill effects as opioids that are controlled under Schedule I of the 1961 Single Convention on Narcotic Drugs. Its use has been reported in a number of countries and has been associated with adverse effects, including death. It has no known therapeutic use and is likely to cause substantial harm.
Recommendation: The Committee recommended that brorphine (IUPAC chemical name: 3- {1- [1- (4-bromophenyl) ethyl] piperidin-4-yl} -1H-benzimidazol-2-one) be added to Schedule I of the 1961 Single Convention on Narcotic Drugs.
ECDD Recommendation
Inclusion in Schedule I and Schedule IV of the 1961 Convention on Narcotic Drugs
Link to full TRS
9789240042834-eng.pdf1.84 MB
MS Questionnaire Report