Brotizolam Stats - Substance Search

Pharmacology

DrugBank

Half-life 4.4 hours. State Solid Vd 0.63 l/kg. Clearance Total clearance: 109 ml/min.

Description

Brotizolam is a sedative-hypnotic thienodiazepine drug which is a benzodiazepine analog. It demonstrates anxiolytic, anticonvulsant, hypnotic, sedative and skeletal muscle relaxant effects. Brotizolam has similar effects to short-acting benzodiazepines such as triazolam. Brotizolam is indicated for 2-4 weeks of treatment for severe or debilitating insomnia. Brotizolam is an extremely potent drug and it is rapidly eliminated with an average half-life of 4.4 hours (range 3.6 - 7.9 hours). Brotizolam is not approved for sale in the UK, United States or Canada but is sold in the Netherlands, Germany, Spain, Belgium, Austria, Portugal, Israel, Italy and Japan.

Metabolism

There are two primary metabolites: 1-methyl-hydroxy- and the 4-hydroxy-derivatives (Eberts et al., 1981; Boehringer Ingelheim, product information). The 4-hydroxymetabolites have a pharmacological activity which is far less than that of the parent drugs, but the 1-methyl-hydroxymetabolites probably have comparable activity (Gall et al., 1978; Jochemsen et al., 1982; Sethy & Harris, 1982; Jochemsen et al., unpublished results). These active compounds are, however, not present in plasma in measurable amounts following a single dose of brotizolam to young healthy subjects (Jochemsen et al., 1982; Jochemsen et al., unpublished results).

Absorption

The plasma concentration profile of brotizolam can be described as a one compartmental open model with first-order absorption.

Indication

Brotizolam is indicated for 2-4 weeks in the treatment of severe or debilitating insomnia.

Protein Binding

The mean value of the free fraction (%): 8.4 ± 0.7.

Receptor Profile

Receptor Actions

Modulators

GABA-A receptor positive allosteric modulator (benzodiazepine site)

History & Culture

1974–1984

Brotizolam was first patented in 1974. The compound's synthesis was subsequently documented by Weber, Bauer, Danneberg, and Kuhn through a 1978 United States patent. The substance entered clinical practice a decade after its initial patent in 1984, finding adoption primarily in European markets and Japan as a prescription hypnotic medication.

1988–1993

Brotizolam became subject to regulatory scrutiny in Hong Kong during the late 1980s and early 1990s following emerging patterns of misuse. In October 1990, the Pharmacy and Poisons Board responded by reclassifying brotizolam alongside triazolam and flunitrazepam as Dangerous Drugs, instituting requirements for formal prescriptions and detailed record-keeping for the supply and dispensing of these substances. Analysis of sales patterns between 1990 and 1993 revealed mixed outcomes from this initial intervention. While flunitrazepam and triazolam sales declined in 1991, five unrestricted benzodiazepines saw increased sales during the same period. New problems emerged with nimetazepam trafficking and temazepam misuse that year. These developments prompted the extension of the regulatory framework to encompass all benzodiazepines by January 1992. The comprehensive prescription and record-keeping requirements appear to have partially curbed benzodiazepine misuse in Hong Kong, though some ongoing concerns with temazepam, nimetazepam, triazolam, and brotizolam remained.

Effect Profile

Curated + 1 Reports

Benzodiazepine 7.3

Strong anxiolysis, euphoria, and cognitive impairment with mild sedation

Anxiolysis×3

10

Sedation / Relaxation×2

5

Motor / Cognitive Impairment×1

9

Euphoria / Mood Lift×1

10

Based on reports from:

Erowid Experience Reports PsychonautWiki Brotizolam

Tolerance & Pharmacokinetics

drugs.wiki

Half-Life

3–6 hours (can be longer in hepatic impairment)

Addiction Potential

Moderate to high, as with other short-acting benzodiazepine analogues; frequent or high-dose use can lead to tolerance, physiological dependence, and a withdrawal syndrome.

Tolerance Decay

Full tolerance 14d Half tolerance 7d Baseline ~28d

As with other benzodiazepines, tolerance to sedative/hypnotic effects tends to accrue over days to weeks of regular use and decays over several weeks of abstinence. Cross‑tolerance within the class is expected; the quantitative ratios are approximate and based on clinical and community observations, not controlled head‑to‑head trials.

Cross-Tolerances

Other benzodiazepines

80% ●○○

Z-drugs

50% ●○○

Experience Report Analysis

Erowid

1 Reports

2012–2012 Date Range

1 With Age Data

Demographics

Gender Distribution

Age Distribution

Reports Over Time

Benzodiazepine Equivalence

0.25 mg Brotizolam = 10.0 mg Diazepam

Potency ratio 40.0

Bioavailability Oral 70% +/- 24%.

Brotizolam - 0.25mg ~=10mg Diazepam.

⚠ All other CNS depressants.

Legal Status

Country	Status	Notes
Austria	Prescription medicine	Approved for medical use and available by prescription.
Belgium	Prescription medicine	Available as an approved prescription medicine for therapeutic applications.
Canada	Not approved	Brotizolam has not received approval for sale or prescription use in Canada.
Germany	Prescription medicine	Approved for medical use and available through prescription from licensed practitioners.
Hong Kong	Dangerous Drug	Reclassified as a Dangerous Drug by the Pharmacy and Poisons Board in October 1990 following concerns about benzodiazepine abuse. Detailed records are required for supply and dispensing alongside formal prescriptions.
Israel	Prescription medicine	Approved for sale and available by prescription for medical purposes.
Italy	Prescription medicine	Approved for sale and available through medical prescription.
Japan	Prescription medicine	Approved for medical use and available as a prescription medication.
Luxembourg	Prescription medicine	Approved for sale and dispensed as a prescription medication.
Netherlands	Prescription medicine	Approved for sale and available as a prescription medication for therapeutic use.
Portugal	Prescription medicine	Available as an approved prescription medication for therapeutic use.
Spain	Prescription medicine	Approved for sale as a prescription medication for legitimate medical purposes.
Taiwan	Prescription medicine	Approved for sale and available as a prescription medication.
United Kingdom	Not approved	Not approved for sale or medical use in the UK. The substance is not available through legitimate pharmaceutical channels.
United States	Not approved	Brotizolam has not been approved for medical use or sale. It remains unavailable as a prescription medication in the US market.

Harm Reduction

drugs.wiki

• Very potent hypnotic; tablets are small doses by design. For naïve or sensitive users, do not exceed 0.125 mg initially and allow the full 2 hours to gauge effects before considering any increase. This reduces blackout risk and cumulative sedation.

• Measurable CNS depression occurs at typical doses; combining with alcohol substantially increases subjective sedation and prolongs/elvates plasma levels versus placebo, raising impairment and overdose risk. Avoid alcohol for the entire night when brotizolam is used.

• Co-use with opioids (including tramadol and methadone) or other depressants (GHB/GBL, barbiturates, sedating antihistamines) is a leading cause of life-threatening respiratory depression; treat such combos as dangerous.

• Metabolized primarily via CYP3A pathways; strong CYP3A4 inhibitors (e.g., azole antifungals, macrolide antibiotics, grapefruit) can raise brotizolam exposure; inducers (e.g., carbamazepine, rifampin) can reduce effects. If unavoidable, lower doses and extra spacing are prudent.

• Onset is often ~15–30 minutes with peak around 1 hour; next-morning impairment of reaction time and tracking can persist, especially at higher doses or with alcohol. Do not drive or operate machinery until you feel fully alert the next day.

• In liver impairment, elimination can be prolonged (reports up to ~13 h). Elderly or debilitated patients should start at 0.125 mg or lower.

• Tolerance to hypnotic effects can emerge within 1–2 weeks of nightly use; dependence can form with regular use. Limit continuous use to the shortest possible period and avoid unplanned escalations.

• Do not stop abruptly after repeated use; taper gradually to reduce rebound insomnia, anxiety, and seizure risk.

• Use pharmaceutical product where possible. If handling non‑RX powders or liquids, employ calibrated scales and consider volumetric dosing for sub‑milligram accuracy to prevent accidental overdosing.

• Contraindications parallel benzodiazepines: severe respiratory disease, significant hepatic dysfunction, pregnancy/lactation, and narrow‑angle glaucoma warrant avoidance unless directed by a clinician.

Brotizolam Stats & Data