|Systematic (IUPAC) name|
|Trade names||Etilaam, Etizest|
|Oral, sublingual, rectal|
6.2 hours(main metabolite is 8.2 hours)
|ATC code||N05BA19 (WHO)|
|Molar mass||342.07 g/mol|
|(what is this?)|
Etizolam (marketed under the brand name Etilaam, Etizola, Sedekopan, Etizest, Pasaden or Depas) is a benzodiazepine analog. The etizolam molecule differs from a benzodiazepine in that the benzene ring has been replaced by a thiophene ring and triazole ring has been fused, making the drug a thienotriazolodiazepine. It possesses amnesic, anxiolytic, anticonvulsant, hypnotic, sedative and skeletal muscle relaxant properties.
- Short-term treatment of insomnia
- Short-term treatment of anxiety or panic attacks, if a benzodiazepine is required
- Anxiety disorders associated with depression: 1 mg two to three times a day (maximum 3 mg per day)
- For panic disorder (associated with agoraphobia): 0.5 mg two times per day (maximum 1 mg per day)
- For insomnia: 1–2 mg once daily before bedtime
Tolerance, dependence and withdrawal
Abrupt or rapid withdrawal from etizolam, as with benzodiazepines, may result in the appearance of the benzodiazepine withdrawal syndrome, including rebound insomnia. Neuroleptic malignant syndrome, a rare event in benzodiazepine withdrawal, has been documented in a case of abrupt withdrawal from etizolam. This is particularly relevant given etizolam's short half life relative to benzodiazepines such as diazepam resulting in a more rapid drug level decrease in blood plasma levels.
In a study that compared the effectiveness of etizolam, alprazolam, and bromazepam for the treatment of generalized anxiety disorder, all three drugs retained their effectiveness over 2 weeks, but etizolam became more effective from 2 weeks to 4 weeks, a type of reverse tolerance. Administering .5 mg etizolam twice daily did not induce cognitive deficits over 3 weeks when compared to placebo.
When multiple doses of etizolam, or lorazepam, were administered to rat neurons, lorazepam caused downregulation of alpha-1 benzodiazepine binding sites (tolerance/dependence), while etizolam caused an increase in alpha-2 benzodiazepine binding sites (reverse tolerance to anti-anxiety effects). Tolerance to the anticonvulsant effects of lorazepam was observed, but no significant tolerance to the anticonvulsant effects of etizolam was observed. Etizolam therefore has a reduced liability to induce tolerance, and dependence, compared with classic benzodiazepines.
Contraindications and special caution
Etizolam is metabolized by the liver and is contraindicated in those with severely impaired hepatic function. It may impair the ability to drive and operate machinery so caution should be applied. Elderly patients should start on a lower dose as they are more susceptible to the sedative effects of etizolam. It is not recommended to be taken during pregnancy or breastfeeding.
Etizolam can increase the sedative and antidepressant actions of other medication such as neuroleptics, analgesics, anaesthetics, antiepileptics, sedatives and first-generation antihistamines. Co-administration with these medications should be avoided unless instructed by a medical professional. Alcohol should also be avoided.
Etizolam, a thienodiazepine derivative, is absorbed fairly rapidly, with peak plasma levels achieved between 30 minutes and 2 hours. It has a mean elimination half life of about 3.5 hours. Etizolam possesses potent hypnotic properties, and is comparable with other short-acting benzodiazepines. Etizolam acts as a full agonist at the benzodiazepine receptor to produce its range of therapeutic and adverse effects. Similar to most other benzodiazepines (exceptions include quazepam) etizolam binds non-selectively to benzodiazepine receptor subtypes.[dubious ]
According to the Italian P.I. sheet, etizolam belongs to a new class of diazepines, thienotriazolodiazepines. This new class is easily oxidized, rapidly metabolized, and has a lower risk of accumulation, even after prolonged treatment. Etizolam has an anxiolytic action about 6 times greater than that of diazepam. Etizolam produces, especially at higher dosages, a reduction in time taken to fall asleep, an increase in total sleep time, and a reduction in the number of awakenings. During tests, there were no substantial changes in deep sleep; however, it may reduce REM sleep. In EEG tests of healthy volunteers, etizolam showed some similar characteristics to tricyclic antidepressants.
Etizolam is not authorized by the FDA for medical use in the U.S. However, it currently remains unscheduled and is legal for research purposes. As it is a thienodiazepine, an analog of benzodiazepines, which are Schedule IV drug under Federal Scheduling Guidelines, it does not fall under the Federal Analog Act, which only applies to Schedule I and II drugs.
Unlike other thienodiazepines such as brotizolam and clotiazepam, etizolam is not controlled under the Misuse of Drugs Act 1971 or licensed as a medicine in the United Kingdom. Etizolam is, however, in scope of the Psychoactive Substances Act 2016, thus making its importation and sale illegal across the United Kingdom.
Etizolam was controlled in Germany in July 2013.
Itraconazole and fluvoxamine slow down the rate of elimination of etizolam, leading to accumulation of etizolam, therefore increasing its pharmacological effects. Carbamazepine speeds up the metabolism of etizolam, resulting in reduced pharmacological effects.
Etizolam, similarly to other GABAergic agonists including benzodiazepines has a strong synergistic effect with ethanol and the consequences of co-ingestion of the two drugs can drastically compound the side effects of either drug.[medical citation needed] This can result in (among other effects) anterograde amnesia (blackouts) and severe respiratory depression which in extreme cases can lead to death.[medical citation needed]
Cases of intentional suicide by overdose using etizolam in combination with GABA agonists have been reported. Although etizolam has a lower LD50 than certain benzodiazepines, the LD50 is still far beyond the prescribed or recommended dose. Flumazenil, a GABA antagonist agent used to reverse benzodiazepine overdoses, inhibits the effect of etizolam as well as classical benzodiazepines such as diazepam and chlordiazepoxide.
Etizolam is a drug of potential abuse. Cases of etizolam dependence have been documented in the medical literature. However, conflicting reports from the World Health Organization, made public in 1991, dispute the abuse claims.
- Benzodiazepine dependence
- Benzodiazepine withdrawal syndrome
- Long-term effects of benzodiazepines
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