Bromazolam: Difference between revisions

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{{MedTemplate

| generic = Bromazolam

| brand = (none — never marketed)

| brand = (none, never marketed)

| structure = Triazolobenzodiazepine; 8-bromo analog of alprazolam (bromine in place of the chloro substituent at the 8-position).

| classes = Designer benzodiazepine, Triazolobenzodiazepine, Sedative-Hypnotic, Research material

| mechanism = Positive allosteric modulator of the GABAA receptor at the benzodiazepine binding site; increases frequency of Cl− channel opening, producing anxiolytic, sedative, hypnotic, anticonvulsant, and skeletal-muscle relaxant effects.

| uses = No approved medical ~~indication~~. Encountered as a designer/research benzodiazepine and, increasingly, as an adulterant in illicit opioid supplies.

| uses = No approved medical problem. Encountered as a designer/research benzodiazepine and, increasingly, as an adulterant in illicit opioid supplies.

| starting_dose = No medical dose. Active recreational doses reported in the 0.5–1.5 mg range (similar potency to alprazolam).

| preparations = Illicit tablets ("bars"), powders, blotter, occasionally solutions. No pharmaceutical product exists.

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| halflife = Estimated ~12–17 h (some sources cite up to ~21 h); active metabolites prolong effect.

| bioavailability = Not formally characterized in humans.

| pregnancy = Avoid. Benzodiazepines are associated with neonatal sedation, floppy-infant syndrome, and withdrawal; teratogenic signal weak but non-zero. Designer benzo with no safety data — assume worst-case.

| pregnancy = Avoid. Benzodiazepines are associated with neonatal sedation, floppy-infant syndrome, and withdrawal; teratogenic signal weak but non-zero. Designer benzo with no safety data, assume worst-case.

| legal = First synthesized by Upjohn in 1976; never marketed. Schedule I in several U.S. states (e.g., Virginia, Florida, Mississippi, Alabama); federally unscheduled in the U.S. as of mid-2020s but DEA has listed it as a med of concern. Class C in the UK (generic benzodiazepine controls). Controlled in Sweden, Germany (NpSG), Switzerland, and Canada.

| intro = '''Bromazolam''' is a triazolobenzodiazepine first synthesized by Upjohn in 1976 and never developed clinically. It emerged on the research-chemical market around 2016 and, beginning around 2021–2022, became one of the most commonly encountered designer benzodiazepines in North America — notably as an adulterant in the illicit opioid supply alongside fentanyl and, often, xylazine. Pharmacologically and structurally it is the bromine analog of alprazolam, with comparable potency and a similar (or somewhat longer) duration of action.

| intro = '''Bromazolam''' is a triazolobenzodiazepine first synthesized by Upjohn in 1976 and never developed clinically. It emerged on the research-chemical market around 2016 and, beginning around 2021–2022, became one of the most commonly encountered designer benzodiazepines in North America, notably as an adulterant in the illicit opioid supply alongside fentanyl and, often, xylazine. Pharmacologically and structurally it is the bromine analog of alprazolam, with comparable potency and a similar (or somewhat longer) duration of action.

| pharmacokinetics = Lipophilic; orally bioavailable; hepatic metabolism (CYP3A4 predominantly) with hydroxylated metabolites. Half-life appears longer than alprazolam, with case reports of detection in blood/urine for days after a single exposure. Standard benzodiazepine immunoassay screens frequently '''miss''' bromazolam — confirmatory LC-MS/MS is required for reliable detection.

| pharmacokinetics = Lipophilic; orally bioavailable; hepatic metabolism (CYP3A4 predominantly) with hydroxylated metabolites. Half-life appears longer than alprazolam, with case reports of detection in blood/urine for days after a single exposure. Standard benzodiazepine immunoassay screens frequently '''miss''' bromazolam, confirmatory LC-MS/MS is required for reliable detection.

| pharmacodynamics = Non-selective positive allosteric modulator at the benzodiazepine site of GABAA receptors containing α1, α2, α3, or α5 subunits with a γ subunit. Like alprazolam, clinically displays anxiolytic, hypnotic, anticonvulsant, amnestic, and muscle-relaxant effects with significant abuse liability. Respiratory depression at high doses is modest in isolation but markedly synergized by opioids, alcohol, and other CNS depressants — the dominant mechanism of bromazolam-associated mortality.

| pharmacodynamics = Non-selective positive allosteric modulator at the benzodiazepine site of GABAA receptors containing α1, α2, α3, or α5 subunits with a γ subunit. Like alprazolam, clinically displays anxiolytic, hypnotic, anticonvulsant, amnestic, and muscle-relaxant effects with significant abuse liability. Respiratory depression at high doses is modest in isolation but markedly synergized by opioids, alcohol, and other CNS depressants, the dominant mechanism of bromazolam-associated mortality.

| indications = None approved. Has no recognized medical role.

| dosing = No therapeutic dosing. Harm-reduction note: because of inconsistent tablet purity and frequent fentanyl co-contamination, '''any''' illicit "benzo" tablet should be assumed to potentially contain bromazolam, fentanyl, or both.

| effects = Sedation, anxiolysis, anterograde amnesia, ataxia, slurred speech, disinhibition, prolonged blackouts. At high dose or in combination: severe sedation, respiratory depression, coma. Paradoxical agitation/aggression occasionally reported. Withdrawal mirrors other high-potency benzos: anxiety, insomnia, autonomic hyperactivity, seizures, delirium — and can be life-threatening, often more protracted than alprazolam withdrawal owing to the longer half-life.

| effects = Sedation, anxiolysis, anterograde amnesia, ataxia, slurred speech, disinhibition, prolonged blackouts. At high dose or in combination: severe sedation, respiratory depression, coma. Paradoxical agitation/aggression occasionally reported. Withdrawal mirrors other high-potency benzos: anxiety, insomnia, autonomic hyperactivity, seizures, delirium, and can be life-threatening, often more protracted than alprazolam withdrawal owing to the longer half-life.

| interactions = <pharmaInteractions/>

* '''Opioids''' (fentanyl, heroin, methadone, buprenorphine): profound additive respiratory depression — primary mechanism of bromazolam-associated overdose death.

* '''Opioids''' (fentanyl, heroin, methadone, buprenorphine): profound additive respiratory depression, primary mechanism of bromazolam-associated overdose death.

* '''Alcohol, GHB, barbiturates, gabapentinoids''': additive CNS/respiratory depression.

* '''Xylazine''': frequently co-encountered in illicit opioid supply ("tranq dope"); compounds sedation and complicates resuscitation (xylazine is not reversed by naloxone).

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* '''Flumazenil''' reverses GABAA effects but is rarely used in mixed-overdose / chronic-benzo contexts due to seizure risk.

| pregnancy_details = Avoid in pregnancy and lactation. Class data extrapolated from clinical benzodiazepines; designer status means no formal safety data.

| monitoring = In suspected overdose: airway, respiratory rate, oxygen saturation, mental status. Standard urine benzodiazepine immunoassay is '''insensitive''' to bromazolam — request specific LC-MS/MS confirmation. ECG and electrolytes if mixed overdose suspected.

| monitoring = In suspected overdose: airway, respiratory rate, oxygen saturation, mental status. Standard urine benzodiazepine immunoassay is '''insensitive''' to bromazolam, request specific LC-MS/MS confirmation. ECG and electrolytes if mixed overdose suspected.

| counseling = Patients should be counseled that illicit "Xanax bars" or designer benzodiazepine tablets are frequently bromazolam and/or fentanyl. Never combine with opioids or alcohol. Withdrawal requires medically supervised taper — do not stop abruptly after sustained use. Carry naloxone if any opioid co-use is plausible (naloxone does '''not''' reverse bromazolam itself but reverses concurrent opioid depression).

| counseling = Patients should be counseled that illicit "Xanax bars" or designer benzodiazepine tablets are frequently bromazolam and/or fentanyl. Never combine with opioids or alcohol. Withdrawal requires medically supervised taper, do not stop abruptly after sustained use. Carry naloxone if any opioid co-use is plausible (naloxone does '''not''' reverse bromazolam itself but reverses concurrent opioid depression).

| anecdotes =

| seealso = [[Alprazolam]], [[Clonazolam]], [[Flualprazolam]], [[Etizolam]], [[Flumazenil]], [[Fentanyl]], [[Xylazine]], [[Naloxone]]

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[[Category:Research ~~Materials~~]]

[[Category:Research chemicals]]

[[Category:Benzodiazepines]]

[[Category:Triazolobenzodiazepines]]

[[Category:GABAA Positive Allosteric Modulators (General)]]

[[Category:GABAergics]]

[[Category:~~Anxiolytics &~~ Sedative-~~Hypnotics~~]]

[[Category:Sedative-hypnotics]]

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