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Brotizolam

Lendormin, Lendorm, Lindormin, Bondormin, Noctilan

Psychoactive Class

Sedative Anxiolytic Depressant

Chemical Class

Thienotriazolodiazepine

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

Dosage & Duration

Dosage

Threshold~80 µg

Light100-200 µg

Moderate200-400 µg

Strong400-600 µg

Heavy600+ µg

Duration

After Effects1-4 hours

Half-life

3.6-7.9 hours

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.

Sedation

Sedation is the defining physical effect, appropriate to a hypnotic used for sleep induction.

Uncomfortable

Dizziness Headaches

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.

Confusion

Visual

Visual effects are not a typical feature of brotizolam.

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.

Interactions

Caution

Use caution

These 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.

1,2-BenzodiazepineAbametapirAcetazolamideAcetophenazineAgomelatine

TripSit

Tolerance

Full Tolerance

Tolerance to the hypnotic effects develops with repeated use, which is why clinical treatment is typically limited to 2-4 weeks to minimize tolerance development and dependence.

Cross Tolerance

Benzodiazepines, Thienodiazepines, Other GABA-A positive allosteric modulators

Harm Potential

Addiction & Dependence

Psychological

Moderate

Brotizolam 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

Moderate

Physical 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

Development and Commercialization

Brotizolam was first patented in 1974.⁷ The compound's synthesis was subsequently documented by Weber, Bauer, Danneberg, and Kuhn through a 1978 United States patent.⁷ The substance entered clinical practice a decade after its initial patent in 1984,

Legality

By Country

United StatesNot approved

Brotizolam has not been approved for medical use or sale. It remains unavailable as a prescription medication in the US market.²⁵

BelgiumLegal (regulated)Annex III psychotropic

Royal Decree of 6 September 2017 regulating narcotic drugs and/or psychotropic substances, Annex III⁹¹⁰

Brotizolam is listed by name in Annex III of Belgium's Royal Decree of 6 September 2017. The decree requires prior activity authorization for regulated products, while acquisition or possession of legally obtained medicines is excepted from that authorization requirement.

GermanyPrescription onlySchedule III

Betäubungsmittelgesetz (BtMG), Anlage III and § 13¹²¹³

Brotizolam is listed in Anlage III of Germany's Narcotics Act (BtMG). The schedule exempts preparations containing no other Schedule I–III substance and up to 0.02 percent or 0.25 mg brotizolam per divided form. Non-exempt Schedule III narcotics may be prescribed only by physicians, dentists, or veterinarians when medically justified, and pharmacies dispense them against a prescription.

IsraelPrescription medicineCitation needed

Approved for sale and available by prescription for medical purposes.

JapanPrescription medicine

Approved for medical use and available as a prescription medication.¹⁵

NetherlandsPrescription medicine

Approved for sale and available as a prescription medication for therapeutic use.⁸

PortugalPrescription medicine

Available as an approved prescription medication for therapeutic use.⁸

SpainPrescription medicine

Approved for sale as a prescription medication for legitimate medical purposes.⁸

UkraineRestrictedTable I · List 2

Cabinet of Ministers Resolution No. 770 of 6 May 2000, Table III List 2²²

Brotizolam is listed in Table III, List 2 of Ukraine's controlled-substances schedule. This list covers psychotropic substances whose circulation is restricted and for which exceptions to some control measures may be permitted.

AustriaPrescription medicine

Approved for medical use and available by prescription.⁸

CanadaRestrictedtargeted substance

Benzodiazepines and Other Targeted Substances Regulations¹¹

Canada treats brotizolam as a benzodiazepine and other targeted substance under the Benzodiazepines and Other Targeted Substances Regulations. Licensed-dealer authorization covers activities including production, import, export, sale, transport, and destruction of targeted substances. Imports and exports require permits that are available only to licensed dealers.

Hong KongDangerous Drug

Reclassified as a Dangerous Drug by the Pharmacy and Poisons Board in October 1990 following concerns about benzodiazepine abuse.⁶¹⁴ Detailed records are required for supply and dispensing alongside formal prescriptions.⁶

ItalyPrescription medicine

Approved for sale and available through medical prescription.⁸

LuxembourgPrescription medicine

Approved for sale and dispensed as a prescription medication.⁸

PolandPrescription onlyGroup IV-P

Rozporządzenie Ministra Zdrowia z 17 sierpnia 2018 r. w sprawie wykazu substancji psychotropowych, środków odurzających oraz nowych substancji psychoaktywnych, załącznik nr 1, grupa IV-P; ustawa o przeciwdziałaniu narkomanii, art. 33 i 41¹⁶¹⁷

Brotizolam is listed as a Group IV-P psychotropic substance in the Minister of Health's schedule. Group IV-P psychotropic substances may be used only for medical, industrial, or research purposes. Preparations containing Group IV-P psychotropic substances are dispensed by pharmacies on prescription.

SingaporePrescription onlyPrescription-only

Poisons Rules (rule 15; Third Schedule)¹⁸¹⁹

Brotizolam is included in the Third Schedule of Singapore’s Poisons Rules. Rule 15 requires poisons in that Schedule to be sold on and in accordance with a prescription given by a medical practitioner, dentist or veterinary surgeon.

TaiwanRestrictedFourth-level controlled drug

管制藥品分級及品項 (Controlled Drugs Classification and Items), Fourth-level controlled drugs, item 72²⁰²¹

Brotizolam is listed as item 72 of Taiwan's fourth-level controlled drugs. Taiwan's Controlled Drugs Management Act limits controlled drugs to medical and scientific need and requires authorization for the import, export, manufacture, sale, and purchase of fourth-level controlled drugs.

United KingdomRestrictedClass C · Schedule 4 Part I

Misuse of Drugs Act 1971, Schedule 2 Part III (Class C); Misuse of Drugs Regulations 2001, Schedule 4 Part I²³²⁴

Brotizolam is a Class C controlled drug and is listed in Part I of Schedule 4 to the Misuse of Drugs Regulations 2001.

References

Source Pages

Citations

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