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Title: Etizolam  
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Subject: Chlormezanone, Gidazepam, Cloxazolam, List of benzodiazepines, Tetrabamate
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Systematic (IUPAC) name
7-(2-Chlorophenyl)-4-ethyl-13-methyl-3-thia-1,8,11,12-tetraazatricyclo[,6] trideca-2(6),4,7,10,12-pentaene
Clinical data
Trade names Etilaam
Pregnancy cat.
  • N
Legal status
  • UK: Unscheduled
  • US: Unscheduled
Routes Oral, Sublingual, Rectal
Pharmacokinetic data
Bioavailability 93%
Metabolism Hepatic

3.4 hours

(main metabolite is 8.2 hours)
Excretion Renal
CAS number  YesY
ATC code N05
ChemSpider  YesY
Chemical data
Formula C17H15ClN4S 
Mol. mass 342.07

Etizolam (marketed under the brand name Etilaam, Etizest, Etizola, Sedekopan, Pasaden or Depas) is a benzodiazepine analog.[1] The etizolam molecule differs from a benzodiazepine in that the benzene ring has been replaced by a thiophene ring, making the drug a thienodiazepine.[2] It possesses amnesic, anxiolytic, anticonvulsant, hypnotic, sedative and skeletal muscle relaxant properties.[3]



  • 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[6]

A 1 mg dose of etizolam is approximately equivalent to a 10 mg dose of diazepam, see List of benzodiazepines.

Side effects

Very Rare

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.[9] Neuroleptic malignant syndrome, a rare event in benzodiazepine withdrawal, has been documented in a case of abrupt withdrawal from etizolam.[10]

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.[11] Administering .5 mg etizolam twice daily did not induce cognitive deficits over 3 weeks when compared to placebo.[12]

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).[13] Tolerance to the anticonvulsant effects of lorazepam were observed, but no significant tolerance to the anticonvulsant effects of etizolam were observed.[13] Etizolam therefore has a reduced liability to induce tolerance, and dependence, compared with classical benzodiazepines.[13]

Contraindications and special caution


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.[14] Etizolam possesses potent hypnotic properties,[15] and is comparable with other short-acting benzodiazepines.[14] Etizolam acts as a full agonist at the benzodiazepine receptor to produce its range of therapeutic and adverse effects.[16] Similar to other benzodiazepines, etizolam binds non-selectively to benzodiazepine receptor subtypes.[17]

In addition, etizolam, unlike most other benzodiazepines (some of which can increase levels of estradiol), has prolactogenic effects, leading to an increase in blood levels of prolactin.[18]

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 not substantial changes in deep sleep; however, it may reduce REM sleep. In EEG tests of healthy volunteers, etizolam showed some characteristics of tricyclic antidepressants.[5]

Legal status

United States

As of August 2014 Etizolam is not authorized for medical use in the U.S. However, it currently remains unscheduled and is legal for research purposes. As its closest derivative is a 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.[19]

The state of Arkansas has proposed listing Etizolam as a Schedule I drug under their drug scheduling guidelines[20] along with the state of Mississippi .[21]


Etizolam was controlled in Germany in July 2013.[22]


Etizolam may be scheduled under the Act on Counteracting Drug Addiction and the State Sanitary Inspection -Article 27c


Itraconazole and fluvoxamine slow down the rate of elimination of etizolam, leading to accumulation of etizolam, therefore increasing its pharmacological effects.[23][24] Carbamazepine speeds up the metabolism of etizolam, resulting in reduced pharmacological effects.[25]

Etizolam, similarly to other GABAergic agonists including the 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. This can result in (among other effects) anterograde amnesia (blackouts) and severe respiratory depression which in extreme cases can lead to death.


Cases of intentional suicide by overdose using etizolam have been reported.[26] Although etizolam has a lower LD50 than certain benzodiazepines, the LD50 is still far beyond the prescribed or recommended dose. Many lethal etizolam overdoses were due to drug interactions.


Etizolam is a drug of potential abuse. However, conflicting reports from the World Health Organization, made public in 1991, dispute the abuse claims.[27]

According to the Journal of the American Medical Association, benzodiazepines — either alone or mixed with other drugs — were involved in nearly 30 percent of fatal overdoses in the United States in 2010. A Japanese study published in Forensic Science International revealed that metabolic traces of etizolam were detected in two people who died of lethal drug overdoses. Fast-acting benzodiazepines may produce side effects very quickly, especially if the user is taking other drugs.

See also


  1. ^ DE 2229845 
  2. ^ Niwa T, Shiraga T, Ishii I, Kagayama A, Takagi A (September 2005). "Contribution of human hepatic cytochrome p450 isoforms to the metabolism of psychotropic drugs" (PDF). Biol. Pharm. Bull. 28 (9): 1711–6.  
  3. ^ Mandrioli R, Mercolini L, Raggi MA (October 2008). "Benzodiazepine metabolism: an analytical perspective". Curr. Drug Metab. 9 (8): 827–44.  
  4. ^ Lopedota A, Cutrignelli A, Trapani A, et al. (May 2007). "Effects of different cyclodextrins on the morphology, loading and release properties of poly (DL-lactide-co-glycolide)-microparticles containing the hypnotic agent etizolam". J Microencapsul 24 (3): 214–24.  
  5. ^ a b "Depas". Retrieved February 3, 2009. 
  6. ^ Pharmaceuticals, Intas. "Etilaam - .25mg, .50mg,.1mg". Etilaam's prescribing info sheet for doctors in India. Intas Pharmaceuticals. 
  7. ^ Wakakura M, Tsubouchi T, Inouye J (March 2004). "Etizolam and benzodiazepine induced blepharospasm". J. Neurol. Neurosurg. Psychiatr. 75 (3): 506–7.  
  8. ^ Kuroda K, Yabunami H, Hisanaga Y (January 2002). "Etizolam-induced superficial erythema annulare centrifugum". Clin. Exp. Dermatol. 27 (1): 34–6.  
  9. ^ Hirase M, Ishida T, Kamei C (November 2008). "Rebound insomnia induced by abrupt withdrawal of hypnotics in sleep-disturbed rats". Eur. J. Pharmacol. 597 (1–3): 46–50.  
  10. ^ Kawajiri M, Ohyagi Y, Furuya H, et al. (February 2002). "[A patient with Parkinson's disease complicated by hypothyroidism who developed malignant syndrome after discontinuation of etizolam]". Rinsho Shinkeigaku (in Japanese) 42 (2): 136–9.  
  11. ^ Bertolino, A; Mastucci, E; Porro, V; Corfiati, L; Palermo, M; Ecari, U; Ceccarelli, G (1989). "Etizolam in the treatment of generalized anxiety disorder: A controlled clinical trial". The Journal of international medical research 17 (5): 455–60.  
  12. ^ De Candia, MP; Di Sciascio, G; Durbano, F; Mencacci, C; Rubiera, M; Aguglia, E; Garavini, A; Bersani, G; Di Sotto, A; Placidi, G; Cesana, BM (2009). "Effects of treatment with etizolam 0.5 mg BID on cognitive performance: A 3-week, multicenter, randomized, double-blind, placebo-controlled, two-treatment, three-period, noninferiority crossover study in patients with anxiety disorder". Clinical therapeutics 31 (12): 2851–9.  
  13. ^ a b c Sanna, E; Busonero, F; Talani, G; Mostallino, MC; Mura, ML; Pisu, MG; MacIocco, E; Serra, M; Biggio, G (2005). "Low tolerance and dependence liabilities of etizolam: Molecular, functional, and pharmacological correlates". European Journal of Pharmacology 519 (1–2): 31–42.  
  14. ^ a b Fracasso C, Confalonieri S, Garattini S, Caccia S (1991). "Single and multiple dose pharmacokinetics of etizolam in healthy subjects". Eur. J. Clin. Pharmacol. 40 (2): 181–5.  
  15. ^ Nakamura J, Mukasa H (December 1992). "Effects of thienodiazepine derivatives, etizolam and clotiazepam on the appearance of Fm theta". Jpn. J. Psychiatry Neurol. 46 (4): 927–31.  
  16. ^ Yakushiji T, Fukuda T, Oyama Y, Akaike N (November 1989). "Effects of benzodiazepines and non-benzodiazepine compounds on the GABA-induced response in frog isolated sensory neurones". Br. J. Pharmacol. 98 (3): 735–40.  
  17. ^ Ozawa M, Nakada Y, Sugimachi K, et al. (March 1994). "Pharmacological characterization of the novel anxiolytic beta-carboline abecarnil in rodents and primates". Jpn. J. Pharmacol. 64 (3): 179–87.  
  18. ^ Kaneda Y (2000). "Short Communication: Prolactogenic effects of etizolam". Neuro Endocrinol. Lett. 21 (6): 475–476.  
  19. ^
  20. ^
  21. ^
  22. ^ and
  23. ^ Araki K, Yasui-Furukori N, Fukasawa T, et al. (August 2004). "Inhibition of the metabolism of etizolam by itraconazole in humans: evidence for the involvement of CYP3A4 in etizolam metabolism". Eur. J. Clin. Pharmacol. 60 (6): 427–30.  
  24. ^ Suzuki Y, Kawashima Y, Shioiri T, Someya T (December 2004). "Effects of concomitant fluvoxamine on the plasma concentration of etizolam in Japanese psychiatric patients: wide interindividual variation in the drug interaction". Ther Drug Monit 26 (6): 638–42.  
  25. ^ Kondo S, Fukasawa T, Yasui-Furukori N, et al. (May 2005). "Induction of the metabolism of etizolam by carbamazepine in humans". Eur. J. Clin. Pharmacol. 61 (3): 185–8.  
  26. ^ Nakamae T, Shinozuka T, Sasaki C, et al. (November 2008). "Case report: Etizolam and its major metabolites in two unnatural death cases". Forensic Sci. Int. 182 (1–3): e1–6.  
  27. ^ WHO Expert Committee on Drug Dependence

External links

  • - Etizolam
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