Estazolam

Last updated
Estazolam
Estazolam.svg
Estazolam3d.png
Clinical data
Trade names Prosom, Esilgan, Eurodin, Nuctalon, others
Other namesDesmethylalprazolam
AHFS/Drugs.com Monograph
MedlinePlus a691003
License data
Routes of
administration 		By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 93%
Metabolism Liver
Elimination half-life 10–24 hours
Excretion Kidney
Identifiers
  • 8-chloro-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.045.424 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C16H11ClN4
Molar mass 294.74 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 Yes check.svgY
  • Key:CDCHDCWJMGXXRH-UHFFFAOYSA-N Yes check.svgY
   (verify)

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.

Contents

It was patented in 1968 and came into medical use in 1975. [4]

Medical uses

Estazolam 1mg pills, sold as Eurodin, from Japan. Estazolam (eurodin).jpg
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. [5] [6] 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. [7] Estazolam also has anxiolytic properties and due to its long half life can be an effective short-term treatment for insomnia associated with anxiety. [8]

Side effects

A hang-over effect commonly occurs with next day impairments of mental and physical performance. [9] Other side effects of estazolam include somnolence, dizziness, hypokinesia, and abnormal coordination. [10]

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. [11]

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. [12] [13] 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. [14]

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. [15]

Pharmacology

Estazolam is classed as a "triazolo" benzodiazepine drug. [16] Estazolam exerts its therapeutic effects via its benzodiazepines receptor agonist properties. [17] Estazolam at high doses decreases histamine turnover via its action at the benzodiazepine-GABA receptor complex in mouse brains. [18]

Pharmacokinetics

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. [19] [20] The major metabolite of estazolam is 4-hydroxyestazolam. [21] Other identified metabolites include 1-oxo-estazolam, 4'-hydroxy-estazolam, and benzophenone. [3]

Interactions

Alcohol enhances the sedative hypnotic properties of estazolam. [22] 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. [23]

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. [24]

Abuse

A primate study found that estazolam has abuse potential. [25] 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. [26] 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. [27] In 2007, a Canadian product called Sleepees was recalled after it was found to contain undeclared estazolam. [28] [29]

See also

Related Research Articles

<span class="mw-page-title-main">Benzodiazepine</span> Class of depressant drugs

Benzodiazepines, colloquially called "benzos", are a class of depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat conditions such as anxiety disorders, insomnia, and seizures. The first benzodiazepine, chlordiazepoxide (Librium), was discovered accidentally by Leo Sternbach in 1955 and was made available in 1960 by Hoffmann–La Roche, who soon followed with diazepam (Valium) in 1963. By 1977, benzodiazepines were the most prescribed medications globally; the introduction of selective serotonin reuptake inhibitors (SSRIs), among other factors, decreased rates of prescription, but they remain frequently used worldwide.

<span class="mw-page-title-main">Hypnotic</span> Drug whose use induces sleep

Hypnotic, or soporific drugs, commonly known as sleeping pills, are a class of psychoactive drugs whose primary function is to induce sleep and to treat insomnia (sleeplessness).

<span class="mw-page-title-main">Temazepam</span> Insomnia medication

Temazepam, sold under the brand name Restoril among others, is a medication of the benzodiazepine class which is generally used to treat severe or debilitating insomnia. It is taken by mouth. Temazepam is rapidly absorbed, and significant hypnotic effects begin in less than 30 minutes and can last for up to eight hours. Prescriptions for hypnotics such as temazepam have seen a dramatic decrease since 2010, while anxiolytics such as alprazolam, clonazepam, and lorazepam have increased or remained stable. Temazepam and similar hypnotics, such as triazolam (Halcion) are generally reserved for severe and debilitating insomnia. They have largely been replaced by z-drugs and atypical antidepressants as first line treatment for insomnia.

<span class="mw-page-title-main">Alprazolam</span> Benzodiazepine medication

Alprazolam, sold under the brand name Xanax, is a fast-acting, potent tranquilizer of moderate duration within the triazolobenzodiazepine group of chemicals called benzodiazepines. Alprazolam is most commonly used in management of anxiety disorders, specifically panic disorder or generalized anxiety disorder (GAD). Other uses include the treatment of chemotherapy-induced nausea, together with other treatments. GAD improvement occurs generally within a week. Alprazolam is generally taken orally.

<span class="mw-page-title-main">Zolpidem</span> Hypnotic medication

Zolpidem, sold under the brand name Ambien among others, is a medication primarily used for the short-term treatment of sleeping problems. Guidelines recommend that it be used only after cognitive behavioral therapy for insomnia and behavioral changes, such as sleep hygiene, have been tried. It decreases the time to sleep onset by about fifteen minutes and at larger doses helps people stay asleep longer. It is taken by mouth and is available in conventional tablets, sublingual tablets, or oral spray.

<span class="mw-page-title-main">Triazolam</span> Triazolobenzodiazepine class medication

Triazolam, sold under the brand name Halcion among others, is a central nervous system (CNS) depressant tranquilizer of the triazolobenzodiazepine (TBZD) class, which are benzodiazepine (BZD) derivatives. It possesses pharmacological properties similar to those of other benzodiazepines, but it is generally only used as a sedative to treat severe insomnia. In addition to the hypnotic properties, triazolam's amnesic, anxiolytic, sedative, anticonvulsant, and muscle relaxant properties are pronounced as well.

<span class="mw-page-title-main">Zopiclone</span> Hypnotic medication

Zopiclone, sold under the brand name Imovane among others, is a nonbenzodiazepine used to treat difficulty sleeping. Zopiclone is molecularly distinct from benzodiazepine drugs and is classed as a cyclopyrrolone. However, zopiclone increases the normal transmission of the neurotransmitter gamma-aminobutyric acid (GABA) in the central nervous system, via modulating GABAA receptors similarly to the way benzodiazepine drugs do.

<span class="mw-page-title-main">Nitrazepam</span> Benzodiazepine sedative

Nitrazepam, sold under the brand name Mogadon among others, is a hypnotic drug of the benzodiazepine class used for short-term relief from severe, disabling anxiety and insomnia. It also has sedative (calming) properties, as well as amnestic, anticonvulsant, and skeletal muscle relaxant effects.

<span class="mw-page-title-main">Flurazepam</span> Hypnotic medication

Flurazepam is a drug which is a benzodiazepine derivative. It possesses anxiolytic, anticonvulsant, hypnotic, sedative and skeletal muscle relaxant properties. It produces a metabolite with a long half-life, which may stay in the bloodstream for days. Flurazepam was patented in 1968 and came into medical use the same year. Flurazepam, developed by Roche Pharmaceuticals, was one of the first benzodiazepine hypnotic medications to be marketed.

<span class="mw-page-title-main">Zaleplon</span> Medication used to treat insomnia

Zaleplon, sold under the brand name Sonata among others, is a sedative and hypnotic which is used to treat insomnia. It is a nonbenzodiazepine or Z-drug of the pyrazolopyrimidine class. It was developed by King Pharmaceuticals and approved for medical use in the United States in 1999.

<span class="mw-page-title-main">Nonbenzodiazepine</span> Class of psychoactive drugs

Nonbenzodiazepines, sometimes referred to colloquially as Z-drugs, are a class of psychoactive drugs that are benzodiazepine-like in uses, such as for treating insomnia and anxiety.

<span class="mw-page-title-main">Quazepam</span> Benzodiazipine

Quazepam, sold under brand name Doral among others, is a relatively long-acting benzodiazepine derivative drug developed by the Schering Corporation in the 1970s. Quazepam is used for the treatment of insomnia including sleep induction and sleep maintenance. Quazepam induces impairment of motor function and has relatively selective hypnotic and anticonvulsant properties with considerably less overdose potential than other benzodiazepines. Quazepam is an effective hypnotic which induces and maintains sleep without disruption of the sleep architecture.

<span class="mw-page-title-main">Loprazolam</span> Benzodiazepine

Loprazolam (triazulenone) marketed under many brand names is a benzodiazepine medication. It possesses anxiolytic, anticonvulsant, hypnotic, sedative and skeletal muscle relaxant properties. It is licensed and marketed for the short-term treatment of moderately-severe insomnia.

<span class="mw-page-title-main">Etizolam</span> Benzodiazepine analog drug

Etizolam is a thienodiazepine 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 triazole ring has been fused, making the drug a thienotriazolodiazepine.

<span class="mw-page-title-main">Lormetazepam</span> Benzodiazepine medication

Lormetazepam, sold under the brand name Noctamid among others, is a drug which is a short to intermediate acting 3-hydroxy benzodiazepine derivative and temazepam analogue. It possesses hypnotic, anxiolytic, anticonvulsant, sedative, and skeletal muscle relaxant properties.

<span class="mw-page-title-main">Brotizolam</span> Benzodiazepine

Brotizolam is a sedative-hypnotic thienotriazolodiazepine drug which is a benzodiazepine analog. It possesses anxiolytic, anticonvulsant, hypnotic, sedative and skeletal muscle relaxant properties, and is considered to be similar in effect to other short-acting hypnotic benzodiazepines such as triazolam or midazolam. It is used in the short-term treatment of severe insomnia. Brotizolam is a highly potent and short-acting hypnotic, with a typical dose ranging from 0.125 to 0.25 milligrams, which is rapidly eliminated with an average half-life of 4.4 hours.

<span class="mw-page-title-main">Bretazenil</span> Chemical compound

Bretazenil (Ro16-6028) is an imidazopyrrolobenzodiazepine anxiolytic drug which is derived from the benzodiazepine family, and was invented in 1988. It is most closely related in structure to the GABA antagonist flumazenil, although its effects are somewhat different. It is classified as a high-potency benzodiazepine due to its high affinity binding to benzodiazepine binding sites where it acts as a partial agonist. Its profile as a partial agonist and preclinical trial data suggests that it may have a reduced adverse effect profile. In particular bretazenil has been proposed to cause a less strong development of tolerance and withdrawal syndrome. Bretazenil differs from traditional 1,4-benzodiazepines by being a partial agonist and because it binds to α1, α2, α3, α4, α5 and α6 subunit containing GABAA receptor benzodiazepine receptor complexes. 1,4-benzodiazepines bind only to α1, α2, α3 and α5GABAA benzodiazepine receptor complexes.

<span class="mw-page-title-main">Haloxazolam</span> Benzodiazepine

Haloxazolam, is a drug which is a benzodiazepine derivative. It has similar hypnotic properties as the benzodiazepine drugs triazolam, temazepam, and flunitrazepam and as such is indicated for the treatment of insomnia. A study in cats comparing estazolam and haloxazolam found that haloxazolam only affects gamma motor neurons, whereas estazolam affects both alpha and gamma motor neurons.

<span class="mw-page-title-main">Benzodiazepine dependence</span> Medical condition

Benzodiazepine dependence defines a situation in which one has developed one or more of either tolerance, withdrawal symptoms, drug seeking behaviors, such as continued use despite harmful effects, and maladaptive pattern of substance use, according to the DSM-IV. In the case of benzodiazepine dependence, the continued use seems to be typically associated with the avoidance of unpleasant withdrawal reaction rather than with the pleasurable effects of the drug. Benzodiazepine dependence develops with long-term use, even at low therapeutic doses, often without the described drug seeking behavior and tolerance.

<span class="mw-page-title-main">Somnifacient</span> Class of medications that induce sleep

Somnifacient, also known as sedatives or sleeping pills, is a class of medications that induces sleep. It is mainly used for treatment of insomnia. Examples of somnifacients include benzodiazepines, barbiturates and antihistamines.

References

  1. ↑ 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.
  2. ↑ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA . Retrieved 22 Oct 2023.
  3. 1 2 "Estazolam tablet". DailyMed. 30 September 2020. Retrieved 25 October 2020.
  4. ↑ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 538. ISBN   9783527607495.
  5. ↑ Roehrs T, Zorick F, Lord N, Koshorek GL, Roth T (June 1983). "Dose-related effects of estazolam on sleep of patients with insomnia". Journal of Clinical Psychopharmacology. 3 (3): 152–156. doi:10.1097/00004714-198306000-00002. PMID   6135720. S2CID   9143614.
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ Post GL, Patrick RO, Crowder JE, Houston J, Ferguson JM, Bielski RJ, et al. (August 1991). "Estazolam treatment of insomnia in generalized anxiety disorder: a placebo-controlled study". Journal of Clinical Psychopharmacology. 11 (4): 249–253. doi:10.1097/00004714-199108000-00005. PMID   1918423. S2CID   7890993.
  9. ↑ 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.
  10. ↑ Pierce MW, Shu VS, Groves LJ (March 1990). "Safety of estazolam. The United States clinical experience". The American Journal of Medicine. 88 (3A): 12S–17S. doi:10.1016/0002-9343(90)90280-Q. PMID   1968713.
  11. ↑ "FDA expands Boxed Warning to improve safe use of benzodiazepine drug". U.S. Food and Drug Administration (FDA). 23 September 2020. Retrieved 23 September 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  12. ↑ Kirkwood CK (1999). "Management of insomnia". Journal of the American Pharmaceutical Association. 39 (5): 688–96, quiz 713–4. doi:10.1016/S1086-5802(15)30354-5. PMID   10533351.
  13. ↑ Lee YJ (2004). "Overview of the therapeutic management of insomnia with zolpidem". CNS Drugs. 18 (Suppl 1): 17–23, discussion 41, 43–5. doi:10.2165/00023210-200418001-00005. PMID   15291010. S2CID   7936406.
  14. ↑ Grad RM (November 1995). "Benzodiazepines for insomnia in community-dwelling elderly: a review of benefit and risk". The Journal of Family Practice. 41 (5): 473–481. PMID   7595266.
  15. ↑ Authier N, Balayssac D, Sautereau M, Zangarelli A, Courty P, Somogyi AA, et al. (November 2009). "Benzodiazepine dependence: focus on withdrawal syndrome". Annales Pharmaceutiques Françaises. 67 (6): 408–413. doi:10.1016/j.pharma.2009.07.001. PMID   19900604.
  16. ↑ Braestrup C, Squires RF (April 1978). "Pharmacological characterization of benzodiazepine receptors in the brain". European Journal of Pharmacology. 48 (3): 263–270. doi:10.1016/0014-2999(78)90085-7. PMID   639854.
  17. ↑ 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.
  18. ↑ 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.
  19. ↑ Allen MD, Greenblatt DJ, Arnold JD (1979). "Single- and multiple-dose kinetics of estazolam, a triazolo benzodiazepine". Psychopharmacology. 66 (3): 267–274. doi:10.1007/BF00428318. PMID   43552. S2CID   23882114.
  20. ↑ Mancinelli A, Guiso G, Garattini S, Urso R, Caccia S (March 1985). "Kinetic and pharmacological studies on estazolam in mice and man". Xenobiotica; The Fate of Foreign Compounds in Biological Systems. 15 (3): 257–265. doi:10.3109/00498258509045357. PMID   2862746.
  21. ↑ Miura M, Otani K, Ohkubo T (May 2005). "Identification of human cytochrome P450 enzymes involved in the formation of 4-hydroxyestazolam from estazolam". Xenobiotica; The Fate of Foreign Compounds in Biological Systems. 35 (5): 455–465. doi:10.1080/00498250500111612. PMID   16012077. S2CID   10576075.
  22. ↑ Wang JS, DeVane CL (2003). "Pharmacokinetics and drug interactions of the sedative hypnotics" (PDF). Psychopharmacology Bulletin. 37 (1): 10–29. doi:10.1007/BF01990373. PMID   14561946. S2CID   1543185. Archived from the original (PDF) on 2007-07-09.
  23. ↑ Miura M, Ohkubo T, Sugawara K, Okuyama N, Otani K (May 2002). "Determination of estazolam in plasma by high-performance liquid chromatography with solid-phase extraction" (PDF). Analytical Sciences. 18 (5): 525–528. doi: 10.2116/analsci.18.525 . PMID   12036118.
  24. ↑ Watanabe S, Ohta H, Sakurai Y, Takao K, Ueki S (July 1986). "[Electroencephalographic effects of 450191-S and its metabolites in rabbits with chronic electrode implants]". Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica. 88 (1): 19–32. doi: 10.1254/fpj.88.19 . PMID   3758874.
  25. ↑ Johanson CE (March 1987). "Benzodiazepine self-administration in rhesus monkeys: estazolam, flurazepam and lorazepam". Pharmacology, Biochemistry, and Behavior. 26 (3): 521–526. doi:10.1016/0091-3057(87)90159-6. PMID   2883668. S2CID   21917850.
  26. ↑ Griffiths RR, Johnson MW (2005). "Relative abuse liability of hypnotic drugs: a conceptual framework and algorithm for differentiating among compounds". The Journal of Clinical Psychiatry. 66 (Suppl 9): 31–41. PMID   16336040.
  27. ↑ Food and Drug Administration; U.S. Department of Health and Human Services (10 March 1998). "FDA WARNS CONSUMERS AGAINST TAKING DIETARY SUPPLEMENT "SLEEPING BUDDHA"". FDA. Archived from the original on October 6, 2008. Retrieved 21 December 2008.
  28. ↑ "Potentially habit-forming herbal sleep aid recalled". CBC News. Feb 23, 2007. Retrieved 2020-07-03.
  29. ↑ André P (Aug 14, 2007). "Losing sleep over 'natural' aids". The Globe and Mail. Retrieved 2020-07-03.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.