Brotizolam
Brotizolam is a sedative-hypnotic of the thienotriazolodiazepine class, a benzodiazepine analog patented in 1974 and introduced into medical use in 1984.1 It is prescribed for short-term treatment of severe insomnia in parts of Europe, Israel, and Japan. Brotizolam is notable for its exceptional potency and rapid elimination, producing effects comparable to triazolam and midazolam. As with other benzodiazepines, it carries risks of respiratory depression when combined with other depressants, as well as amnesia and habit formation.2
Contents
Dosage & Duration
Dosage
Duration
Subjective Effects
Brotizolam produces an experience dominated by rapid, heavy sedation and anxiety relief, consistent with its use as a highly potent, short-acting hypnotic for severe insomnia. Its character closely resembles short-acting benzodiazepines such as triazolam, with pronounced hypnotic, muscle relaxant, and amnesic components and little in the way of sensory alteration. Residual effects such as drowsiness and impaired cognitive and motor function can persist into the following day, particularly at doses above 0.5–1 mg.
Physical
The body load centers on strong sedation and skeletal muscle relaxation, accompanied by ataxia, clumsiness, slurred speech, and general impairment of motor function. Dizziness, fatigue, and headache are common, while nausea, vomiting, palpitations, hypotension, and respiratory depression occur less often.
Cognitive
The headspace is calm and anxiety-suppressed but clouded, with confusion and anterograde amnesia commonly accompanying moderate to high doses. Paradoxical reactions such as anxiety, aggression, or violent behavior occur infrequently.
Paradoxical
Paradoxical reactions occur in a minority of users.
Suppressions
Suppressive effects dominate the mental state, in line with the compound's hypnotic and anxiolytic profile.
Visual
Visual effects are not a typical feature of brotizolam.
Reagent Testing
Loading reagent data
Pharmacology
Pharmacodynamics
Brotizolam acts as a positive allosteric modulator of the GABA-A receptor at the benzodiazepine binding site.1 Through this mechanism, it produces anxiolytic, anticonvulsant, hypnotic, sedative, and skeletal muscle relaxant effects.1 It is considered pharmacologically similar to other short-acting hypnotic benzodiazepines such as triazolam and midazolam.
Pharmacokinetics
Brotizolam is rapidly absorbed following administration and is rapidly eliminated, with an average half-life of 4.4 hours (range 3.6–7.9 hours).34 It is metabolized into two primary metabolites: a 4-hydroxy derivative with far less potency than the parent compound, and a 1-methylhydroxy derivative thought to have comparable activity. However, the 1-methylhydroxy metabolite is not present in measurable plasma concentrations following a single dose in healthy subjects, so neither metabolite contributes significantly to the overall pharmacological effect in humans.
Caution
Use cautionThese combinations are not usually physically harmful, but may produce undesirable effects, such as physical discomfort or overstimulation. Extreme use may cause physical health issues. Synergistic effects may be unpredictable. Care should be taken when choosing to use this combination.
Tolerance
Benzodiazepines, Thienodiazepines, Other GABA-A positive allosteric modulators
Harm Potential
Addiction & Dependence
Psychological
ModerateBrotizolam has recognized potential for abuse and is classified as habit-forming.5 Abuse was significant enough in Hong Kong during the late 1980s and 1990s to warrant government reclassification as a Dangerous Drug, with regulatory controls subsequently extended to all benzodiazepines.6
Physical
ModeratePhysical dependence can develop with regular use.5 Treatment is recommended for only 2-4 weeks for severe insomnia.5 Mild rebound insomnia may occur when treatment is stopped, indicating physiological adaptation to the drug.1
Psychosis Risk
Hallucinations and paradoxical reactions including aggression, anxiety, and violent behavior are listed as less common side effects.5 These psychiatric disturbances appear to be uncommon at recommended doses.
History & Culture
Legality
By Country
References
Source Pages
Citations
- (February 1988). Brotizolam. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy as an hypnotic. Drugs, 35(2), 104–22. https://doi.org/10.2165/00003495-198835020-0000212345
- (n.d.). Brotizolam (PIM 919). International Programme on Chemical Safety (INCHEM/WHO). https://www.inchem.org/documents/pims/pharm/pim919.htm1
- Bechtel WD, Ohnhaus EE, & Jochemsen R. (1983). Pharmacokinetics and metabolism of brotizolam in humans. 16(Suppl 2), 279S–283S. https://doi.org/10.1111/j.1365-2125.1983.tb02301.x12
- Klotz U, Ziegler G, Ludwig L, & Reimann IW. (1983). Pilot pharmacokinetic study of brotizolam, a thienodiazepine hypnotic, using electron-capture gas-liquid chromatography. https://pubmed.ncbi.nlm.nih.gov/6844800/12
- (2009). Lendormin 0.25mg tablets (Brotizolam) – Core Safety Profile, European PSUR Work Sharing Project. College ter Beoordeling van Geneesmiddelen (CBG-MEB). https://db.cbg-meb.nl/veegactie/csp/brotizolam-3-2009.pdf1234
- (1995). Use and abuse of benzodiazepines in Hong Kong 1990-1993--the impact of regulatory changes. Journal of Toxicology. Clinical Toxicology, 33(6), 597–602. https://doi.org/10.3109/15563659509010615123456
- (n.d.). 6-Phenyl-8-bromo-4H-s-triazolo-[3,4C]-thieno-[2,3E]-1,4-diazepines and salts thereof. https://patents.google.com/patent/US4094984A12
- European Medicines Agency. (2023-07-06). List of nationally authorised medicinal products: brotizolam, Procedure No. PSUSA/00000444/202212. European Medicines Agency. https://www.ema.europa.eu/en/documents/psusa/brotizolam-list-nationally-authorised-medicinal-products-psusa00000444202212_en.pdf12345678
- Government of Canada. (n.d.). Controlled Drugs and Substances Act, SC 1996, c 19 – Schedule IV. laws-lois.justice.gc.ca. https://laws-lois.justice.gc.ca/eng/acts/c-38.8/page-12.html1
- German Federal Government. (n.d.). Betäubungsmittelgesetz (BtMG) – Anlage III (zu § 1 Abs. 1): verkehrsfähige und verschreibungsfähige Betäubungsmittel. Bundesministerium der Justiz / gesetze-im-internet.de. https://www.gesetze-im-internet.de/btmg_1981/anlage_iii.html1
- Pharmacy Society of Hong Kong. (2011). Consolidated List of Poisons, Antibiotics and Dangerous Drugs – Schedule 1, Part I Dangerous Drugs (Cap.134). Hong Kong Pharmaceutical Journal, 18(4 (Supplement)). http://www.pshk.hk/uploads/files/HKPJ/v18n4supp.pdf1
- (2024). Trends in the multiple prescriptions of hypnotic drugs in a university outpatient in Japan. Neuropsychopharmacology Reports. https://pmc.ncbi.nlm.nih.gov/articles/PMC10932787/1
- Taiwan Food and Drug Administration. (n.d.). 管制藥品分級及品項 (Schedules and Items of Controlled Drugs) – Taiwan Food and Drug Administration. Taiwan Food and Drug Administration. https://www.fda.gov.tw/tc/includes/GetFile.ashx?id=f6371219532100627731
- UK Parliament. (1998). The Misuse of Drugs Act 1971 (Modification) Order 1998, SI 1998/750. legislation.gov.uk. https://www.legislation.gov.uk/uksi/1998/750/made1
- UK Parliament. (2001). The Misuse of Drugs Regulations 2001, SI 2001/3998 – Schedule 4. legislation.gov.uk. https://www.legislation.gov.uk/uksi/2001/3998/schedule/4/made?view=plain1
- National Library of Medicine (US). (2025-03-15). Brotizolam – Drugs and Lactation Database (LactMed®). National Library of Medicine (US). https://www.ncbi.nlm.nih.gov/books/NBK567885/1
Further Reading
Automated synthesisInformation aggregated and synthesized using an autonomous workflow built by Josie Kins.
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