Brotizolam: Wikis

  
  

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Brotizolam
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
Identifiers
CAS number 57801-81-7
ATC code N05CD09
PubChem 2451
DrugBank ?
ChemSpider 2357
Chemical data
Formula C 15H10BrClN4S 
Mol. mass 393.7 g/mol
SMILES eMolecules & PubChem
Pharmacokinetic data
Bioavailability 48-95%
Metabolism Hepatic
Half life 4.4 hours (range, 2.6–6.9 h)
Excretion Renal
Therapeutic considerations
Pregnancy cat.  ?
Legal status Schedule IV (US)
Routes Oral

Brotizolam (marketed under brand name Lendormin) is a sedative-hypnotic[1] thienodiazepine drug which is a benzodiazepine analog.[2] 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.[3] 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.

Contents

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.[4]

Premedication. Brotizolam can be used as a premedication prior to surgery.[5]

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.[6]

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.[7]

Pharmacology

Brotizolam has been shown in animal studies to be a very high potency benzodiazepine.[8] 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.[2] Brotizolam induces impairment of motor function and has hypnotic properties.[9] 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.[10]

Commercial names

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

See also

Notes

  1. ^ Fink, M; Irwin (1981). "Pharmacoelectroencephalographic study of brotizolam, a novel hypnotic". Clinical pharmacology and therapeutics 30 (3): 336–42. PMID 7273596.  
  2. ^ a b Jochemsen, R; Wesselman; Van Boxtel; Hermans; Breimer (1983). "Comparative pharmacokinetics of brotizolam and triazolam in healthy subjects." (PDF). British journal of clinical pharmacology 16 Suppl 2: 291S–297S. PMID 6140948. http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1428224&blobtype=pdf.  
  3. ^ Mandrioli R, Mercolini L, Raggi MA (October 2008). "Benzodiazepine metabolism: an analytical perspective". Curr. Drug Metab. 9 (8): 827–44. doi:10.2174/138920008786049258. PMID 18855614. http://www.benthamdirect.org/pages/content.php?CDM/2008/00000009/00000008/0009F.SGM.  
  4. ^ Rickels K. (1986). "The clinical use of hypnotics: indications for use and the need for a variety of hypnotics". Acta Psychiatrica Scandinavica Suppl. 332: 132–41. doi:10.1111/j.1600-0447.1986.tb08990.x. PMID 2883820.  
  5. ^ Nishiyama T, Yamashita K, Yokoyama T, Imoto A, Manabe M (2007). "Effects of quazepam as a preoperative night hypnotic: comparison with brotizolam" (PDF). J Anesth 21 (1): 7–12. doi:10.1007/s00540-006-0445-2. PMID 17285406. http://www.springerlink.com/content/n18j6x4n0570v711/fulltext.pdf?page=1.  
  6. ^ Nicholson, AN; Stone; Pascoe (1980). "Studies on sleep and performance with a triazolo-1, 4-thienodiazepine (brotizolam)." (PDF). British journal of clinical pharmacology 10 (1): 75–81. PMID 7397057. http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1430017&blobtype=pdf.  
  7. ^ Authier, N.; Balayssac, D.; Sautereau, M.; Zangarelli, A.; Courty, P.; Somogyi, AA.; Vennat, B.; Llorca, PM. et al. (Nov 2009). "Benzodiazepine dependence: focus on withdrawal syndrome.". Ann Pharm Fr 67 (6): 408-13. doi:10.1016/j.pharma.2009.07.001. PMID 19900604.  
  8. ^ Shibuya, T; Field; Watanabe; Sato; Salafsky (1984). "Structure-affinity relationships between several new benzodiazepine derivatives and 3H-diazepam receptor sites.". Japanese journal of pharmacology 34 (4): 435–40. doi:10.1254/jjp.34.435. PMID 6144807.  
  9. ^ Yasui M; Kato A, Kanemasa T, Murata S, Nishitomi K, Koike K, Tai N, Shinohara S, Tokomura M, Horiuchi M, Abe K. (June 2005). "[Pharmacological profiles of benzodiazepinergic hypnotics and correlations with receptor subtypes]". Nihon Shinkei Seishin Yakurigaku Zasshi 25 (3): 143–51. PMID 16045197.  
  10. ^ Noguchi H; Kitazumi K, Mori M, Shiba T. (March 2004). "Electroencephalographic properties of zaleplon, a non-benzodiazepine sedative/hypnotic, in rats" (pdf). J Pharmacol Sci. 94 (3): 246–51. doi:10.1254/jphs.94.246. PMID 15037809. http://www.jstage.jst.go.jp/article/jphs/94/3/246/_pdf.  

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








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