Details
Stereochemistry | ACHIRAL |
Molecular Formula | C15H10BrClN4S |
Molecular Weight | 393.689 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CC1=NN=C2CN=C(C3=C(SC(Br)=C3)N12)C4=C(Cl)C=CC=C4
InChI
InChIKey=UMSGKTJDUHERQW-UHFFFAOYSA-N
InChI=1S/C15H10BrClN4S/c1-8-19-20-13-7-18-14(9-4-2-3-5-11(9)17)10-6-12(16)22-15(10)21(8)13/h2-6H,7H2,1H3
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/3281819Curator's Comment: description was created based on several sources, including
http://www.rad-ar.or.jp/siori/english/print.cgi?n=52
Sources: https://www.ncbi.nlm.nih.gov/pubmed/3281819
Curator's Comment: description was created based on several sources, including
http://www.rad-ar.or.jp/siori/english/print.cgi?n=52
Brotizolam (marketed under brand name Lendormin) is a sedative-hypnotic thienotriazolodiazepine 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 severe or debilitating insomnia and in a dose of 0.25 mg can be used as a premedication prior to surgery, this dose was found to be comparable in efficacy to 2 mg flunitrazepam as a premedicant prior to surgery. The drug was developed by a team led by T Nishiyama while working for Takeda Chemical Industries in 1976 in Japan. Brotizolam is not approved for sale in the UK, United States or Canada. It is approved for sale in the Netherlands, Germany, Spain, Belgium, Luxembourg, Austria, Portugal, Israel, Italy, Taiwan and Japan. Insomnia. Brotizolam is prescribed for the short-term treatment, 2–4 weeks only of severe or debilitating insomnia. Insomnia can be described as a difficulty falling asleep, frequent awakening, early awakenings or a combination of each. Brotizolam inhibits the hypothalamus and cerebral limbic system controlling emotion through GABA, a typical inhibitory transmitter of central nervous system. As a result, unnecessary stimulation from the autonomic nervous system and other sites is blocked, demonstrating central nervous action including hypnosis, sedation and anti-anxiety
CNS Activity
Sources: http://www.ncbi.nlm.nih.gov/pubmed/6151995
Curator's Comment: CNS depressant
Known to be CNS depressant in mice, rats and rabbits. Human data not available
Originator
Sources: https://www.google.com/patents/US4017620
Curator's Comment: # by a team led by T Nishiyama while working for Takeda Chemical Industries in 1976 in Japan
Approval Year
PubMed
Title | Date | PubMed |
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[Perioperative management for nephrectomy using combined spinal-epidural anesthesia with sedation in a patient with cerebral palsy under maintenance hemodialysis]. | 2002 Nov |
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Evaluation of three ancillary treatments in the management of equine grass sickness. | 2002 Sep 28 |
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[Case of prolonged recovery from serotonin syndrome caused by paroxetine]. | 2003 |
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[Investigations of poisonings with benzodiazepine derivatives mixtures by thin-layer chromatography]. | 2003 |
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Zopiclone, but not brotizolam, impairs memory storage during sleep. | 2003 Oct |
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CAP variables and arousals as sleep electroencephalogram markers for primary insomnia. | 2003 Sep |
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Screening, library-assisted identification and validated quantification of 23 benzodiazepines, flumazenil, zaleplone, zolpidem and zopiclone in plasma by liquid chromatography/mass spectrometry with atmospheric pressure chemical ionization. | 2004 Aug |
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Electroencephalographic properties of zaleplon, a non-benzodiazepine sedative/hypnotic, in rats. | 2004 Mar |
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Effect of itraconazole on the pharmacokinetics and pharmacodynamics of a single oral dose of brotizolam. | 2004 Nov |
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Quantitative analysis of 33 benzodiazepines, metabolites and benzodiazepine-like substances in whole blood by liquid chromatography-(tandem) mass spectrometry. | 2004 Nov 5 |
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Inhibition of the metabolism of brotizolam by erythromycin in humans: in vivo evidence for the involvement of CYP3A4 in brotizolam metabolism. | 2005 Aug |
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Improvement of dry mouth by replacing paroxetine with fluvoxamine. | 2005 Mar |
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[Actigraphic assessment of the effects of hypnotics on the night before surgery in relation with the severity of surgery]. | 2005 Nov |
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Diagnostic performance of Triage for benzodiazepines: urine analysis of the dose of therapeutic cases. | 2005 Sep |
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Potentiation of ethanol in spatial memory deficits induced by some benzodiazepines. | 2006 Aug |
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Effect of zolpidem on sleep architecture and its next-morning residual effect in insomniac patients: a randomized crossover comparative study with brotizolam. | 2006 Jan |
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Rifampicin markedly decreases plasma concentration and hypnotic effect of brotizolam. | 2006 Jun |
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Effects of quazepam as a preoperative night hypnotic: comparison with brotizolam. | 2007 |
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Up-regulation of L-type high voltage-gated calcium channel subunits by sustained exposure to 1,4- and 1,5-benzodiazepines in cerebrocortical neurons. | 2007 Dec |
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Absence status associated with focal activity and polydipsia-induced hyponatremia. | 2008 Apr |
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Preliminary effects of pagoclone, a partial GABA(A) agonist, on neuropsychological performance. | 2008 Feb |
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Case report: a case of intractable Meniere's disease treated with autogenic training. | 2008 Jan 25 |
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Evaluation of anxiolytic-like effects of some short-acting benzodiazepine hypnotics in mice. | 2008 Jul |
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Juvenile stress-induced alteration of maturation of the GABAA receptor alpha subunit in the rat. | 2008 Nov |
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Behavioral pharmacological properties after recovery from the loss of righting reflex induced by benzodiazepine receptor agonists in mice. | 2008 Oct |
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Benzodiazepine metabolism: an analytical perspective. | 2008 Oct |
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Influence of serotonergic/noradrenergic gene polymorphisms on nausea and sweating induced by milnacipran in the treatment of depression. | 2009 |
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Simultaneous determination of benzodiazepines and their metabolites in human serum by liquid chromatography-tandem mass spectrometry using a high-resolution octadecyl silica column compatible with aqueous compounds. | 2009 Apr |
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The benzodiazepine brotizolam reduces fear in calves exposed to a novel object test. | 2009 Feb 16 |
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The impact of age on the hypnotic effects of eszopiclone and zolpidem in the guinea pig. | 2009 Jul |
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Impaired prefrontal hemodynamic maturation in autism and unaffected siblings. | 2009 Sep 3 |
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Development of a list of potentially inappropriate drugs for the korean elderly using the delphi method. | 2010 Dec |
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A validated method for simultaneous screening and quantification of twenty-three benzodiazepines and metabolites plus zopiclone and zaleplone in whole blood by liquid-liquid extraction and ultra-performance liquid chromatography- tandem mass spectrometry. | 2010 Jul-Aug |
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Dose-dependent hemodynamic effects of propofol induction following brotizolam premedication in hypertensive patients taking angiotensin-converting enzyme inhibitors. | 2010 May |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: http://www.rad-ar.or.jp/siori/english/print.cgi?n=52
for adults: one tablet (0.25mg of brotizolam) is orally administered once daily at bedtime
Route of Administration:
Oral
In Vitro Use Guide
Sources: http://www.ncbi.nlm.nih.gov/pubmed/6835488
Using slices of the olfactory tubercle, nucleus accumbens and caudate nucleus, the effects of brotizolam on dopaminergic nerve terminals were examined in vitro. Basal release of dopamine was not affected by brotizolam in concentrations up to 10(-6) M; however, K+-stimulated release of dopamine was significantly reduced by brotizolam at 10(-7) M or above. The reduction of K+-stimulated release of dopamine was antagonized by bicuculline, added in the superfusion medium.
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WHO-ATC |
N05CD09
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NCI_THESAURUS |
C1012
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WHO-VATC |
QN05CD09
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C87057
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4549
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m2729
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260-964-5
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BROTIZOLAM
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19790
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T-113
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ACTIVE MOIETY