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About Etizolam

Etizolam, which is marketed under many different brand names, is a derivative of thienodiazepine, similar to benzodiazepine. Etizolam molecules are different from benzodiazepine due to the benzene ring being replaced with a ring fused from thiophene and triazole. This results in the Etizolam drug being classified as a thienotriazolodiazepine. 

The sedative and muscle relaxing properties of Etizolam can assist in the treatment of, or relief from amnesia, anxiety and convulsion. It was approved for medical use in 1983 following a successful patent application in 1972

Medical Uses

Etizolam can be used in the short term for treating insomnia. It can also be used in the short term for the treatment of panic attacks and anxiety, if a benzodiazepine has been recommended for the patient.

Side Effects

If Etizolam is used for prolonged periods it can lead to blepharospasms. Very rarely, use of this drug can result in erythema annulare centrifugum skin lesions.

Etizolam Withdrawal, Tolerance and Dependence

As with benzodiazepines, sudden discontinuation or a fast withdrawal from Etizolam can have the appearance of benzodiazepine withdrawal syndrome, one of the symptoms of which is rebound insomnia. A particularly rare benzodiazepine withdrawal symptom, Neuroleptic Malignant Syndrome, has been recorded during a case of rapid discontinuation of Etizolam. This case is of particular relevance due to Etizolam’s relatively short half life in comparison to benzodiazepines like diazepam; Etizolam decreases in blood plasma levels less rapidly. 

During a comparison study in treating generalized anxiety disorder with Alprazolam, Bromazepam and Etizolam, it was found that all three of the drugs remained effective over 2 weeks. Etizolam, however, became more effective between weeks 2 and 4, displaying a type of reverse-tolerance. Subjects that received 0.5mg of Etizolam two times per day over a 3 week period did not experience any cognitive deficits compared to those given a placebo.

On administering multiple doses of Etizolam or Lorazepam to rat neurons, it was found that:

  • Lorazepam resulted in a down-regulation of Aplha-1 (dependence/tolerance) binding sites.
  • Etizolam resulted in an increase of Alpha-2 (reverse tolerance to anti-anxiety) binding sites.
  • While there was observation of tolerance to anticonvulsant effects of Lorazepam, there was no observation of the same tolerance of Etizolam.

Pharmacology

Etizolam can be absorbed relatively quickly and will reach peak plasma levels between around 30-120 minutes. Its average half life is around 3.5 hours. Etizolam can be comparable to other benzodiazepines that are short-acting in that it has powerful hypnotic properties. At the benzodiazepine receptor, Etizolam acts as an agonist producing both adverse and therapeutic effects.

Thienotriazolodiazepines is new class of diazepines which is easily oxidized, quickly metabolized and has less of an accumulation risk, even after prolonged use. Therefore, Etizolam’s anxiolytic action is around 6 times that of diazepam. Also, at higher doses, Etizolam reduces the time taken to fall asleep; increases sleep time; and reduces the number of awakenings. 

Tests show that Etizolam did not affect deep sleep, but that it possibly reduces REM sleep. When assessed on healthy subjects undergoing ECG tests, it produced similar characteristics as those of tricyclic antidepressants.

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