Triazolam

Triazolam, sold under the brand name Halcion, is a benzodiazepine compound of the triazolobenzodiazepine (TBZD) class.

TBZDs are characterized by distinct attributes like increased potency and additional serotonergic antidepressant qualities.

Triazolam has the standard range of pharmacological effects associated with benzodiazepines. Still, it sets itself apart due to its remarkable potency and its extremely short-acting nature: 0.3 mg of triazolam is roughly equivalent to 10 mg of diazepam, and its elimination half-life is 2-3 hours.

The FDA approves Triazolam for the short-term treatment of insomnia (generally 7 to 10 days) in adults.

Triazolam’s short duration of effects, combined with the fact that it only has one active metabolite, α-hydroxytriazolam, makes it well suited to its role as a hypnotic agent [1].

IUPAC Name: 8-chloro-6-(2-chlorophenyl)-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine

Other Names: Halcion, Apo-Triazo, Hypam, Trilam

Metabolism: The initial step in triazolam metabolism is cytochrome CYP3A4-mediated hydroxylation to form 1-hydroxytriazolam and 4-hydroxytriazolam. Both metabolites are subsequently conjugated to form glucuronides and eventually eliminated through the kidneys.

Duration of Effects: According to the FDA, triazolam has a mean elimination half-life of 1.5 to 5.5. hours, which would make it short-acting regarding the duration of its effects. Triazolam is credited with being the shortest-acting benzodiazepine available in the United States [1].

How Does Triazolam Work?

Triazolam exerts its effects through the standard mechanism of action: binding to the benzodiazepine site of the gamma-aminobutyric acid-A (GABA) receptors in the brain and central nervous system (CNS), and thus enhancing GABA-mediated synaptic inhibition.

In simpler terms, triazolam potentiates the natural inhibitory function of GABA receptors to produce a generalized depressive effect in the brain and CNS. This overall reduction in activity gives rise to the hypnotic, amnesic, anxiolytic, sedative, anticonvulsant, and muscle relaxant properties associated with benzodiazepines.

However, to better understand the nature of triazolam’s functioning, its specific pharmacological and pharmacokinetic characteristics must be considered. Recent research has found that these individual factors are correlated with the given effects and adverse effects profile of any given benzodiazepine [2].

Rapid Absorption + Exceptionally High Potency

triazolam’s defining characteristics are its rapid absorption and short duration of effects. These properties vastly reduce the occurrence of a residual “hang-over” effect,” a common problem associated with longer-lasting hypnotic agents.

It has been found that, in terms of its effects, triazolam causes dose-dependent effects on sleep stages. Triazolam reduces stage ‘wake’ and stage 1 sleep, increases stage 2, and usually has minimal effects on stage 3 and stage 4 sleep [1]. Most laboratory studies have not shown evidence of tolerance to triazolam’s effects on sleep or rebound insomnia upon cessation of treatment.

It has also been found that, compared to flurazepam and nitrazepam, triazolam has less chance of impairing cognitive performance on the day after ingestion.

Regarding pharmacokinetics, triazolam is rapidly absorbed, with an oral dose of 0.88 mg reaching peak plasma concentration in 1.3 hours. Additionally, triazolam is roughly 90% bound to human plasma albumin and distributes widely into bodily tissues [3].

Is Triazolam Safe? Risks & Side Effects

Along with the vast majority of benzodiazepines on the US market, triazolam is currently listed as a Schedule IV substance in the Controlled Substances Act. This would entail triazolam has recognized medical uses but still carries the potential for misuse and physical dependence, albeit to a lesser degree than Schedule III substances.

In general terms, benzodiazepines, when used correctly, are relatively safe compounds and are not likely to cause serious health events. However, a recent explosion in polydrug abuse in the United States has led to a marked increase in the involvement of benzodiazepines in drug overdose fatalities, usually due to concomitant opioid usage.

This situation has degenerated to the point that the FDA is now sternly warning users against this deadly combination as it can easily lead to respiratory depression: the leading cause of death in drug overdoses. In this sense, it is always a good idea to evaluate the abuse potential and risk factors of a benzodiazepine compound.

In the case of triazolam, specific characteristics like extreme potency and a short duration of action make it highly liable to cause physical dependence and abuse compared to other benzodiazepines. Research has shown that short-acting benzodiazepines are more likely to cause inter-dose withdrawal and elicit habitual tendencies from misuse. This, in combination with its potency, make triazolam a dangerous benzodiazepine.

Side Effects of Triazolam

The FDA has identified the following side effects associated with triazolam use:

• Coordination disorders/ataxia
• Dizziness
• Drowsiness
• Headache
• Light-headedness
• Nausea/Vomiting
• Nervousness

Less common side effects may include:

• Confusional states
• Congestion
• Constipation
• Cramps/pain
• Depression
• Dermatitis
• Diarrhea
• Dry mouth
• Dysesthesia
• Euphoria
• Insomnia
• Memory impairment
• Nightmares
• Paresthesia
• Tachycardia
• Taste alterations
• Tinnitus
• Tiredness
• Visual disturbances
• Weakness