Flubromazolam

IUPAC Name

5-pentyl-2-(2-phenylpropan-2-yl)pyrido[4,3-b]indol-1-one

Year(s) and type of review / ECDD meetings
Drug Class
ECDD Recommendation
Inclusion in Schedule II of the 1971 Convention on Psychotropic Substances
Recommendation (from TRS)
Substance identification
Flubromazolam (chemical name: 8-bromo-6-(2-fluorophenyl)-1-methyl-4H- benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepine) is a 1-4 triazolobenzodiazepine. Flubromazolam is a white powder, often sold as a liquid or as tablets.

WHO review history
Flubromazolam 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 has no recognized therapeutic use.

Similarity to known substances and effects on the central nervous system
Flubromazolam is a highly potent benzodiazepine with long-lasting depressant effects on the central nervous system. Flubromazolam enhances the effects of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) by binding at the benzodiazepine site of the GABAA receptor. This mechanism of action, and its effects, are similar to those of the benzodiazepines triazolam and alprazolam, which are controlled under Schedule IV of the 1971 Convention on Psychotropic Substances. A single pharmacokinetics study showed that a dose of 0.5 mg flubromazolam induced strong sedative effects that lasted more than 10 h and caused partial amnesia for more than 24 h. The effects of flubromazolam have been effectively reversed by the benzodiazepine antagonist flumazenil. Reports on online user forums describe benzodiazepine-like effects, including anxiolytic, euphoric and sedative effects.

Dependence potential
No controlled studies have been reported in animals or humans on the dependence potential of flubromazolam, although many online reports describe severe withdrawal symptoms, such as muscle aches, sleeping disorders, severe anxiety and panic attacks, dissociative symptoms, perceptual distortions, cramping, chills, vomiting and risk of seizures. Loss of control of use and rapid onset of tolerance have also been described. The latter suggest that increased dosing and physical dependence are likely.

Actual abuse and/or evidence of likelihood of abuse
No controlled animal or human studies have assessed the abuse potential of flubromazolam. Impaired driving has been reported with flubromazolam as the sole intoxicant. Non-fatal intoxications requiring hospital admission and fatal intoxications due to flubromazolam use have been documented, with central nervous system depression and severe sedation as clinical features of presentation. Flubromazolam can increase unintentional opioid overdoses. Its long half-life may increase the risk of accumulation and of interactions when taken with other drugs. Nonmedical use and seizures due to flubromazolam have been documented in many countries in various regions. It is increasingly sold as falsified pharmaceutical benzodiazepines.

Therapeutic usefulness
Flubromazolam is not known to have any therapeutic use, is not on the WHO Model List of Essential Medicines and has never been marketed as a medicinal product.

Recommendation
Flubromazolam (chemical name: 8-bromo-6-(2-fluorophenyl)-1-methyl-4H- benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepine) is a 1-4 triazolobenzodiazepine with actions and effects very similar to those of benzodiazepines listed under Schedule IV in the Convention on Psychotropic Substances of 1971. It can produce a state of dependence and central nervous system depression, like other benzodiazepines. Reports of abuse, impaired driving and fatal and non-fatal intoxications have been increasing. There is sufficient evidence of its abuse to conclude that it constitutes a significant risk to public health; it has no known therapeutic use. Recommendation: The Committee recommended that flubromazolam (chemical name: 8-bromo-6-(2-fluorophenyl)-1-methyl-4H-benzo[f] [1,2,4]triazolo[4,3- a][1,4]diazepine) be added to Schedule IV of the 1971 Convention on Psychotropic Substances.