Description

Etizolam

Etizolam (marketed under many brand names) is a thieno diazepine derivative which is a benzodiazepine analog. The etizolam molecule differs from a benzodiazepine in that the benzene ring has been replaced by a thiophene ring and the triazole ring has been fused, making the drug a thienotriazolodiazepine. It possesses amnesic, anxiolytic, anticonvulsant, hypnotic, sedative and skeletal muscle relaxant properties.

Medical uses

  • Short-term treatment of insomnia
  • Short-term treatment of anxiety or panic attacks, if a benzodiazepine is required.
  • Short term treatment for air flight fright, homesickness, motion sickness and seasickness (usually 2-week treatment). It may also be useful in altitude sickness in low doses with supplemental oxygen.
  • Short-term to intermediate term treatment of insomnia and parasomnia. Due to reverse tolerance effects. also, it may reduce night terrors in teenagers over the age of 16, although there are limits in dosage and duration of use to prevent full tolerance.
  • Short-term to intermediate base treatment of anxiety or panic attacks, if a thieno diazepine is required usually.
  • Other uses for autism, agitation and irritability at the lowest dose possible.

Side effects

Long term use may result in blepharospasms. Doses of 4 mg or more may cause anterograde amnesia.

In rare cases, erythema annular centrifugum skin lesions have resulted.

Tolerance, dependence, and withdrawal

Abrupt or rapid discontinuation 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.

Pharmacology

Etizolam pills

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’s main metabolites in humans are alpha-hydroxyetizolam and 8-hydroxyetizolam. Alpha-hydroxyetizolam is pharmacologically active and has a half-life of approximately 8.2 hours.

Interactions

Itraconazole and fluvoxamine slow down the rate of elimination of etizolam, leading to the accumulation of etizolam, therefore increasing its pharmacological effects. Carbamazepine speeds up the metabolism of etizolam, resulting in reduced pharmacological effects