Brotizolam

Brotizolam

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Systematic (IUPAC) name
2-Bromo- 4-(2-chlorphenyl)- 9-methyl- 6H-thieno (3,2-f)(1,2,4) triazolo (4,3-a)(1,4)benzodiazepine
Clinical data
Pregnancy category	?
Routes of administration	Oral
Legal status
Legal status	US: Schedule IV
Pharmacokinetic data
Bioavailability	48-95%
Metabolism	Hepatic
Biological half-life	4.4 hours (range, 2.6–6.9 h)
Excretion	Renal
Identifiers
CAS Number	57801-81-7
ATC code	N05CD09 (WHO)
PubChem	CID 2451
DrugBank	?
ChemSpider	2357
Chemical data
Formula	C15H10BrClN4S
Molar mass	393.7 g/mol[[]]

Brotizolam (marketed under brand name Lendormin) is a sedative-hypnotic thienodiazepine 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 short-acting benzodiazepines such as triazolam. It is used in the short term treatment of insomnia although due to its short half life it is considered to have relatively high abuse potential and so would not be a first-line treatment. Brotizolam is a potent drug with a dosage of 0.5 or 1.0 milligrams, but 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. It is approved for sale in the Netherlands, Germany, Portugal, Italy and Japan.

Indications

Insomnia. Brotizolam is prescribed for the short term treatment, 2 - 4 weeks only of moderately severe insomnia. Insomnia can be described as a difficulty falling asleep, frequent awakening, early awakenings or a combination of each. Brotizolam is a short-intermediate acting benzodiazepine and is sometimes used in patients who have difficulty in maintaining sleep or getting to sleep. Hypnotics should only be used on a short term basis or in those with chronic insomnia on an occasional basis.

Premedication. Brotizolam can be used as a premedication prior to surgery.

Side effects

Brotizolam can cause residual side effects the next day such as impaired cognitive and motor functions as well as drowsiness. Disruption of sleep patterns may also occur such as suppression of REM sleep. These side effects are more likely to occur the higher the dose.

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.

Pharmacology

Brotizolam has been shown in animal studies to be a very high potency benzodiazepine. The elimination half life of brotizolam is 3-6 hours. It is absorbed rapidly after administration; after administration it is metabolised into active metabolites, one of which is far less potent than brotizolam and the other is only present in very small amounts in the blood and thus the metabolites of brotizolam do not have any pharmacological effect in humans. Brotizolam induces impairment of motor function and has hypnotic properties. Brotizolam increases the slow wave light sleep (SWLS) in a dose-dependent manner whilst suppressing deep sleep stages. Less time is spent in stages 3 and 4 which are the deep sleep stages when benzodiazepines such as brotizolam are used. Benzodiazepines are therefore not good hypnotics in the treatment of insomnia. The suppression of deep sleep stages by benzodiazepines may be especially problematic to the elderly as they naturally spend less time in the deep sleep stage.

Commercial names

Name	Countries
Bondormin	Israel
Dormex	Chile
Lendorm	Áustria, Denmark
Lendormin	South Africa, Belgium, Germany, Hungary, Italy, Japan, Netherlands, Portugal
Lendormine	Switzerland
Lindormin	Mexico
Noctilan	Chile
Sintonal	Spain

Chemistry

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Weber, K. H.; Bauer, A.; Danneberg, P.; Kuhn, F. J.; 1978, U.S. Patent 4,094,984.

See also

• Benzodiazepines
• Benzodiazepine dependence
• Benzodiazepine withdrawal syndrome
• Long term effects of benzodiazepines
• Midazolam
• Triazolam
• Loprazolam

References

• Greenblatt DJ, Locniskar A, Shader RI. Pilot pharmacokinetic study of brotizolam, a thienodiazepine hypnotic, using electron-capture gas-liquid chromatography. Sleep. 1983;6(1):72-6. PMID 6844800.

• Langley MS, Clissold SP. Brotizolam. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy as an hypnotic. Drugs. 1988 Feb;35(2):104-22.

• Bechtel WD. Pharmacokinetics and metabolism of brotizolam in humans. British Journal of Clinical Pharmacology. 1983;16 Suppl 2:279S-283S.

• Jochemsen R. Pharmacokinetics of brotizolam in healthy subjects following intravenous and oral administration. British Journal of Clinical Pharmacology. 1983;16 Suppl 2:285S-290S.

External links

• Inchem.org - Brotizolam

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