Clinical data
Trade namesProsom, Esilgan, Eurodin, Nuctalon, others
Other namesDesmethylalprazolam
License data
Routes of
By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Elimination half-life10–24 hours
  • 8-chloro-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine
CAS Number
PubChem CID
CompTox Dashboard (EPA)
ECHA InfoCard100.045.424 Edit this at Wikidata
Chemical and physical data
Molar mass294.74 g·mol−1
3D model (JSmol)
  • ClC1=CC2=C(C=C1)N3C=NN=C3CN=C2C4=CC=CC=C4
  • InChI=1S/C16H11ClN4/c17-12-6-7-14-13(8-12)16(11-4-2-1-3-5-11)18-9-15-20-19-10-21(14)15/h1-8,10H,9H2 checkY

Estazolam, sold under the brand name Prosom among others, is a tranquilizer medication of the triazolobenzodiazepine (TBZD) class, which are benzodiazepines (BZDs) fused with a triazole ring. It possesses anxiolytic, anticonvulsant, hypnotic, sedative and skeletal muscle relaxant properties. Estazolam is an intermediate-acting oral benzodiazepine. It is used for short-term treatment of insomnia.

It was patented in 1968 and came into medical use in 1975.[5]

Medical uses

Estazolam 1mg pills, sold as Eurodin, from Japan.

Estazolam is prescribed for the short-term treatment of certain sleep disorders. It is an effective hypnotic drug showing efficacy in increasing the time spent asleep as well as reducing awakenings during the night. Combination with non-pharmacological options for sleep management results in long-term improvements in sleep quality after discontinuation of short-term estazolam therapy.[6][7] Estazolam is also sometimes used as a preoperative sleep aid. It was found to be superior to triazolam in side effect profile in preoperative patients in a trial.[8] Estazolam also has anxiolytic properties and due to its long half life can be an effective short-term treatment for insomnia associated with anxiety.[9]

Side effects

A hang-over effect commonly occurs with next day impairments of mental and physical performance.[10] Other side effects of estazolam include somnolence, dizziness, hypokinesia, and abnormal coordination.[11]

In September 2020, the U.S. Food and Drug Administration (FDA) required the boxed warning be updated for all benzodiazepine medicines to describe the risks of abuse, misuse, addiction, physical dependence, and withdrawal reactions consistently across all the medicines in the class.[12]

Tolerance and dependence

The main safety concern of benzodiazepines such as estazolam is a benzodiazepine dependence and the subsequent benzodiazepine withdrawal syndrome which can occur upon discontinuation of the estazolam. A review of the literature found that long-term use of benzodiazepines such as estazolam is associated with drug tolerance, drug dependence, rebound insomnia and CNS related adverse effects. Estazolam should only be used short term and at the lowest effective dose to avoid complications related to long-term use. Non-pharmacological treatment options however, were found to have sustained improvements in sleep quality.[13][14] The short-term benefits of benzodiazepines on sleep begin to reduce after a few days due to tolerance to the hypnotic effects of benzodiazepines in the elderly.[15]

Contraindications and special caution

Benzodiazepines require special precaution if used in the elderly, during pregnancy, in children, alcohol or drug-dependent individuals and individuals with comorbid psychiatric disorders.[16]


Estazolam is classed as a "triazolo" benzodiazepine drug.[17] Estazolam exerts its therapeutic effects via its benzodiazepines receptor agonist properties.[18] Estazolam at high doses decreases histamine turnover via its action at the benzodiazepine-GABA receptor complex in mouse brains.[19]


Peak plasma levels are achieved within 1–6 hours. Estazolam is an intermediate acting benzodiazepine. The elimination half life of estazolam is an average of 19 hours, with a range of 8–31 hours.[20][21] The major metabolite of estazolam is 4-hydroxyestazolam.[22] Other identified metabolites include 1-oxo-estazolam, 4'-hydroxy-estazolam, and benzophenone.[3]


Alcohol enhances the sedative hypnotic properties of estazolam.[23] In package inserts, the manufacturer clearly warns about an interaction with ritonavir, and although clinical interactions of ritonavir with estazolam have not yet been described, the lack of clinical descriptions of the interactions does not negate the seriousness of the interaction.[24]

EEG effects in rabbits

An animal study in rabbits demonstrated that estazolam induces a drowsy pattern of spontaneous EEG including high voltage slow waves and spindle bursts increase in the cortex and amygdala, while the hippocampal theta rhythm is desynchronized. Also low voltage fast waves occur particularly in the cortical EEG. The EEG arousal response to auditory stimulation and to electric stimulation of the mesencephalic reticular formation, posterior hypothalamus and centromedian thalamus is significantly suppressed. The photic driving response elicited by a flash light in the visual cortex is significantly suppressed by estazolam.[25]


See also: Benzodiazepine drug misuse

A primate study found that estazolam has abuse potential.[26] Two types of drug misuse can occur; recreational misuse, where the drug is taken to achieve a high or when the drug is continued long term against medical advice.[27] Estazolam became notorious in 1998 when a large amount of an 'herbal sleeping mix' called Sleeping Buddha was recalled from the shelves after the FDA discovered that it contained estazolam.[28] In 2007, a Canadian product called Sleepees was recalled after it was found to contain undeclared estazolam.[29][30]

See also


  1. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". FDA. Retrieved 22 Oct 2023.
  2. ^ Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
  3. ^ a b "Estazolam tablet". DailyMed. 30 September 2020. Retrieved 25 October 2020.
  4. ^ "Estazolam (Prosom) Use During Pregnancy". 18 September 2020. Retrieved 25 October 2020.
  5. ^ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 538. ISBN 9783527607495.
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  7. ^ Rosen RC, Lewin DS, Goldberg L, Woolfolk RL (October 2000). "Psychophysiological insomnia: combined effects of pharmacotherapy and relaxation-based treatments". Sleep Medicine. 1 (4): 279–288. doi:10.1016/S1389-9457(00)00042-3. PMID 11040460.
  8. ^ Mauro C, Sperlongano P (September 1987). "[Controlled clinical evaluation of 2 hypnotic triazole benzodiazepines, estazolam and triazolam, used the night before surgical interventions]". Minerva Medica (in Italian). 78 (18): 1381–1384. PMID 2889169.
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  10. ^ Müller KW, Müller-Limmroth W, Strasser H (1982). "[Alterations of sleep stage pattern in human beings and hang-over effects under the influence of estazolam/2nd Comm.: Studies on the hang-over effect in psycho-physiological performance (author's transl)]". Arzneimittel-Forschung (in German). 32 (4): 456–460. PMID 6125155.
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  18. ^ Akbarzadeh T, Tabatabai SA, Khoshnoud MJ, Shafaghi B, Shafiee A (March 2003). "Design and synthesis of 4H-3-(2-phenoxy)phenyl-1,2,4-triazole derivatives as benzodiazepine receptor agonists". Bioorganic & Medicinal Chemistry. 11 (5): 769–773. doi:10.1016/S0968-0896(02)00469-8. PMID 12538007.
  19. ^ Oishi R, Nishibori M, Itoh Y, Saeki K (May 1986). "Diazepam-induced decrease in histamine turnover in mouse brain". European Journal of Pharmacology. 124 (3): 337–342. doi:10.1016/0014-2999(86)90236-0. PMID 3089825.
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  29. ^ "Potentially habit-forming herbal sleep aid recalled". CBC News. Feb 23, 2007. Retrieved 2020-07-03.
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