Clobromazolam (or Phenazolam DM-II-90, BRN 4550445), chemically known as 8-bromo-6-(2-chlorophenyl)-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine, is a novel benzodiazepine that has garnered attention in recent years as a potent sedative and hypnotic drug. Although initially synthesized in the early 1980s, Phenazolam was never developed for clinical use. However, it has recently surfaced on the internet as a designer drug, primarily identified in forensic analyses of seized samples, particularly in Sweden around March 2016. This compound belongs to the broader category of benzodiazepines, a class of psychoactive drugs known for their effects on the central nervous system (CNS), including sedation, muscle relaxation, anxiolysis, and anticonvulsant properties. Chemical Properties and Mechanism of Action Clobromazolam is structurally related to other benzodiazepines like bromazolam and clonazolam. The molecular formula of Phenazolam is C17H12BrClN4, with a molecular weight of 387.7 g/mol. It possesses a triazolo ring fused to a benzodiazepine core, a structural motif responsible for its pharmacological activity. Like other benzodiazepines, Phenazolam functions by enhancing the effect of the neurotransmitter gamma-aminobutyric acid (GABA) at the GABAA receptor. GABA is the primary inhibitory neurotransmitter in the brain, and its increased activity results in the hyperpolarization of neurons, leading to decreased neuronal excitability. This mechanism underlies the sedative, anxiolytic, and muscle-relaxant effects of benzodiazepines. The specific binding of Phenazolam to the benzodiazepine site on the GABAA receptor amplifies GABA’s natural calming effect on the CNS, making it a potent depressant. Pharmacokinetics and Dosage Clobromazolam‘s pharmacokinetics, including absorption, distribution, metabolism, and excretion, have not been extensively studied due to its recent emergence as a designer drug. However, it is presumed to share similar properties with other benzodiazepines. These drugs are typically well-absorbed orally, with peak plasma concentrations occurring within 1 to 3 hours post-ingestion. Benzodiazepines are known to distribute widely across body tissues, particularly binding to plasma proteins and accumulating in fat tissues due to their lipophilic nature. Metabolism of Phenazolam likely occurs in the liver via the cytochrome P450 enzyme system, converting it into various metabolites, some of which may retain pharmacological activity. The elimination half-life of Phenazolam remains unknown but can be hypothesized to be within the range typical of benzodiazepines, from several hours to days, depending on the metabolic rate and individual variability. Due to its potency and lack of standardized therapeutic dosing guidelines, Phenazolam poses significant risks when consumed. Anecdotal reports suggest that even small doses can lead to profound sedative effects. Users experimenting with this substance typically ingest it orally, though the specific dosage can vary widely. Given its potency, the potential for overdose is high, especially when taken in combination with other CNS depressants such as alcohol or opioids. Effects and Side Effects Phenazolam’s primary effects mirror those of other benzodiazepines, albeit with increased potency. These effects include:

1. Sedation and Hypnosis: Phenazolam induces a strong sedative effect, leading to drowsiness and, at higher doses, sleep. This hypnotic effect is one of the primary reasons for its use as a designer drug.
2. Anxiolysis: It reduces anxiety, contributing to its potential misuse in individuals seeking relief from anxiety disorders without medical supervision.
3. Muscle Relaxation: Phenazolam has muscle relaxant properties, which might be perceived as beneficial in alleviating muscle spasms or tension.
4. Amnesia: Like other benzodiazepines, Phenazolam can cause anterograde amnesia, where the individual has difficulty forming new memories after ingestion. This effect is particularly dangerous in unregulated, recreational use.
5. Euphoria: Although less prominent than the sedative effects, some users may experience a sense of euphoria, contributing to its abuse potential.

Side Effects Phenazolam, as with other benzodiazepines, carries a range of side effects, especially when misused or consumed at high doses. Common side effects include:

• Cognitive Impairment: Impaired memory, attention, and cognitive function are well-documented side effects, increasing the risk of accidents and injury.
• Dizziness and Coordination Problems: Users often experience dizziness, lightheadedness, and impaired motor coordination, contributing to a high risk of falls or accidents.
• Respiratory Depression: In high doses or when combined with other depressants, Phenazolam can severely depress respiratory function, leading to life-threatening conditions.
• Paradoxical Reactions: In some individuals, benzodiazepines can cause paradoxical reactions, such as increased anxiety, aggression, or agitation.
• Tolerance and Dependence: Repeated use leads to tolerance, where increasing doses are needed to achieve the same effects. Dependence can develop rapidly, leading to withdrawal symptoms upon cessation, which can be severe and include seizures, agitation, and delirium.

Harm Reduction and Legal Status Given the risks associated with Phenazolam, harm reduction strategies are crucial for individuals who choose to use this substance. Key harm reduction measures include:

• Accurate Dosing: Due to its potency, users should employ precise weighing scales to measure doses accurately. Even small errors in dosing can lead to overdose.
• Avoiding Polydrug Use: Combining Phenazolam with other CNS depressants, such as alcohol, opioids, or other benzodiazepines, significantly increases the risk of respiratory depression and fatal overdose.
• Supervised Use: Using Phenazolam in the presence of others who are aware of its effects can help ensure that emergency medical help can be sought if needed.
• Education: Users should be fully informed about the risks and signs of overdose and the potential for long-term cognitive effects.

Phenazolam is not currently scheduled under the United States Controlled Substances Act but is illegal in some countries, including Serbia and Italy, due to its potential for abuse and lack of medicinal value. It is crucial for users to be aware of the legal status in their respective regions, as possession or distribution could result in legal consequences. Conclusion Phenazolam represents a highly potent and potentially dangerous benzodiazepine that has found its way into the designer drug market. While its sedative and anxiolytic effects may be appealing to some, the risks of cognitive impairment, dependence, and overdose are significant. Without clinical oversight and standard dosing guidelines, the use of Phenazolam poses substantial health risks. Users should be educated on harm reduction strategies and remain aware of the legal implications of its use.

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