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Bromazolam (XLI-268) is a triazolobenzodiazepine (TBZD) which was first synthesised in 1976, however was never ever marketed. It has subsequently been sold as a designer drug, initially being definitively determined by the EMCDDA in Sweden in 2016. It is the bromo instead of chloro analogue of alprazolam and has similar sedative and anxiolytic impacts to it and other benzodiazepines.

Bromazolam is a non subtype selective agonist at the benzodiazepine website of GABAA receptors, with a binding affinity of 2.81 nM at the α1 subtype, 0.69 nM at α2 and 0.62 nM at α5.

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Bromazolam Powder (Chemical Abstracts Service [CAS] registry number: 71368-80-4; CAS name: 8-bromo-1-methyl6-phenyl-4H-S-triazolo[4,3-a][1,4]benzodiazepine) is a triazolobenzodiazepine that was originally developed as a candidate medication but was never approved for use.

Medical uses: Bromazolam Powder

Short-term treatment of insomnia.
Stress and anxiety conditions such as OCD and general stress and anxiety disorder, mostly as a short-term medication to be used simply on an at-need basis.

Negative effects:

Long term use may result in blepharospasms, specifically in women. Dosages of 4 mg or more might trigger anterograde amnesia.
In unusual cases, erythema annulare centrifugum skin sores have resulted.

Tolerance, dependence and withdrawal

Abrupt or quick discontinuation from Bromazolam , similar to benzodiazepines, may result in the look of the benzodiazepine withdrawal syndrome, consisting of rebound insomnia.

This is particularly appropriate provided Bromazolam short half life relative to benzodiazepines such as diazepam resulting in a more fast drug level decrease in blood plasma levels.

In a study that compared the efficiency of etizolam, alprazolam, and bromazepam for the treatment of generalized anxiety disorder, all 3 drugs kept their effectiveness over 2 weeks, but Bromazolam became more effective from 2 weeks to 4 weeks. Administering 0.5 grams Bromazolam two times daily did not induce cognitive deficits over 3 weeks when compared to placebo.

When several dosages of Bromazolam , or lorazepam, were administered to rat nerve cells, lorazepam caused downregulation of alpha-1 benzodiazepine binding sites (tolerance/dependence), while etizolam triggered a boost in alpha-2 benzodiazepine binding websites (reverse tolerance to anti-anxiety impacts).

Tolerance to the anticonvulsant results of lorazepam was observed, but no significant tolerance to the anticonvulsant results of etizolam was observed. Bromazolam therefore has actually a lowered liability to cause tolerance, and dependence, compared with classic benzodiazepines.

Bromazolam might represent a possible anxiolytic of choice with reduced liability to produce tolerance and reliance after long-term treatment of anxiety and tension syndromes.

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Cases of intentional suicide by overdose utilizing Bromazolam in mix with GABA agonists have been reported. Although Bromazolam has a lower LD50 than specific benzodiazepines, the LD50 is still far beyond the prescribed or recommended dose.

Flumazenil, a GABA antagonist agent used to reverse benzodiazepine overdoses, prevents the impact of Bromazolam in addition to classical benzodiazepines such as diazepam and chlordiazepoxide.

Bromazolam overdose deaths are increasing – for instance, the National Records of Scotland report on drug-related deaths, ‘street’ Bromazolam was a consider (“linked in, or possibly contributed to”) 752, or 59%, of drug-related deaths in Scotland in 2019.

It is essential to highlight that more than one drug added to the huge majority of the deaths (by way of contrast, opiates and opioids were a factor in 1092, or 86%, of drug-related deaths).

Bromazolam (CAS 71368-80-4; Name: 8-bromo-1-methyl6-phenyl-4H-S-triazolo[4,3-a][1,4]benzodiazepine) is a triazolobenzodiazepine that was originally developed as a candidate medication but was never approved for use. Bromazolam phase I metabolism is mediated primarily by several isoforms of the CYP450 enzyme system (CYP2B6, CYP2C19, CYP3A4, CYP3A5 and CYP2C9), whereas phase II metabolism involves the isoenzymes UGT1A4 and UGT2810.

What is Bromazolam?

Bromazolam is also structurally related to flubromazepam, from which it differs by the lack of a fluorine at the 2-position of the phenyl ring. Bromazolam is also structurally similar to pyrazolam, whereby the pyridinyl group has been replaced by a phenyl group.

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Bromazolam was first synthesized in the 1970s by Hester et al. A convenient synthesis method has been reported in the patent literature. Introduction of a triazole ring into the 1,4-benzodiazepine precursor (8-bromo-1-methyl-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepine) gave DE(chloro)-bromo-alprazolam. The 1,4 benzodiazepine precursor can be prepared by cyclization of 2-amino-5-bromobenzophenone with chloroacetylchloride.

Where to get Triazolobenzodiazepine

Bromazolam is soluble in dimethylformamide at a concentration of 30 mg/mL, in dimethylsulphoxide at 20 mg/mL, in ethanol at 10 mg/mL, in methanol at 1 mg/mL and in a 1:1 mixture of dimethylformamide and phosphate-buffered saline (pH 7.2) at 0.5 mg/mL.

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Synthetic Bromazolam has been characterized by proton and carbon nuclear magnetic resonance (1H NMR and 13C NMR), mass spectrometry (MS) and infra-red spectroscopy (IR). DE(chloro)-bromo-alprazolam is available as a reference material from various commercial suppliers and is used in routine analysis for forensic and clinical investigations.

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Benzodiazepines (BZDs) act as positive allosteric modulators on the gamma-aminobutyric acid (GABA)_A receptor [1]. GABA represents the main inhibitor neurotransmitter in the brain and plays an important role in modulating the activity of many neurons, including those in the amygdala and prefrontal cortex [1].

How to use Bromazolam?

The GABA_A receptor is a ligand-gated chloride-selective ion channel build-up of five subunits: two α, two ß (the binding site for endogenous neurotransmitter) and one γ. BZDs bind to the pocket created by α and γ subunits and induce a conformational change in the GABA_A receptors.

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Medical uses: Bromazolam Powder

Negative effects:

Long term use may result in blepharospasms, specifically in women. Dosages of 4 mg or more might trigger anterograde amnesia.
In unusual cases, erythema annulare centrifugum skin sores have resulted.

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What is Bromazolam?

Bromazolam is also structurally related to flubromazepam, from which it differs by the lack of a fluorine at the 2-position of the phenyl ring. Bromazolam is also structurally similar to pyrazolam, whereby the pyridinyl group has been replaced by a phenyl group.

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Where to get Triazolobenzodiazepine

Bromazolam is soluble in dimethylformamide at a concentration of 30 mg/mL, in dimethylsulphoxide at 20 mg/mL, in ethanol at 10 mg/mL, in methanol at 1 mg/mL and in a 1:1 mixture of dimethylformamide and phosphate-buffered saline (pH 7.2) at 0.5 mg/mL.

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How to use Bromazolam?

The GABA_A receptor is a ligand-gated chloride-selective ion channel build-up of five subunits: two α, two ß (the binding site for endogenous neurotransmitter) and one γ. BZDs bind to the pocket created by α and γ subunits and induce a conformational change in the GABA_A receptors.

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