|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 The etizolam molecule differs from a benzodiazepine in that the benzene ring has been replaced by a thiophene ring and triazole ring has been fused, making the drug a thienotriazolodiazepine.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
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.
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.
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 of March 2016, etizolam is a controlled substance in the following states: Alabama, Arkansas, Florida, Mississippi, Virginia, and Georgia.
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 may, however, fall under the scope of the Psychoactive Substances Act 2016, thus potentially making its importation and sale illegal across the United Kingdom in some cases.
The Psychoactive Substances Act 2016 exempts "medicinal products" as defined in the Human Medicines Regulations 2012 , and in turn those regulations define a medicinal product as "any substance or combination of substances presented as having properties of preventing or treating disease in human beings" and further defines a prescription only medication as:
"In these Regulations references to a prescription only medicine are to any of the following—
(a)a medicinal product that is covered by an authorisation of which it is a term that the product is to be available only on prescription;
(b)a medicinal product that—
(i)is covered by an EU marketing authorisation, and
(ii)is classified in the authorisation as a prescription only medicine"
Etizolam does have an EU Marketing authorization as it is legally sold in Italy as a prescription only medicine there, and certainly it could be argued that, in its pharmaceutical form, Etizolam tablets is a substance that is being presented as having properties of treating disease in human beings. It could therefore be argued that Etizolam -- at least, in its medicinal product form -- would not fall under the scope of the Psychoactive Substances Act.
Etizolam was controlled in Germany in July 2013.
Etizolam also called Depas, is restricted as a benzodiazepine analogs in Japan from October 2016 onwards.
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.
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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