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=CC=CC=C4Cl
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
DescriptionCurator's Comment: description was created based on several sources, including
http://www.rad-ar.or.jp/siori/english/print.cgi?n=52
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
Approval Year
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
7.3 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6140948/ |
0.5 mg single, oral dose: 0.5 mg route of administration: Oral experiment type: SINGLE co-administered: |
BROTIZOLAM plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
3397 ng × min/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6140948/ |
0.5 mg single, oral dose: 0.5 mg route of administration: Oral experiment type: SINGLE co-administered: |
BROTIZOLAM plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
5488 ng × min/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6661377/ |
0.5 mg single, oral dose: 0.5 mg route of administration: Oral experiment type: SINGLE co-administered: |
BROTIZOLAM plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED |
|
3852 ng × min/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6661377/ |
0.5 mg single, oral dose: 0.5 mg route of administration: Oral experiment type: SINGLE co-administered: |
BROTIZOLAM plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6140948/ |
0.5 mg single, oral dose: 0.5 mg route of administration: Oral experiment type: SINGLE co-administered: |
BROTIZOLAM plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
7.37 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6661376/ |
0.25 mg single, oral dose: 0.25 mg route of administration: Oral experiment type: SINGLE co-administered: |
BROTIZOLAM serum | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
7.61 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6661376/ |
0.25 mg single, oral dose: 0.25 mg route of administration: Oral experiment type: SINGLE co-administered: |
BROTIZOLAM serum | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
6.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6661376/ |
0.25 mg single, oral dose: 0.25 mg route of administration: Oral experiment type: SINGLE co-administered: |
BROTIZOLAM serum | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
Funbound
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
8.4% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6140948/ |
0.5 mg single, oral dose: 0.5 mg route of administration: Oral experiment type: SINGLE co-administered: |
BROTIZOLAM plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
12.4% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6661377/ |
0.5 mg single, oral dose: 0.5 mg route of administration: Oral experiment type: SINGLE co-administered: |
BROTIZOLAM plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED |
|
9.2% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6661377/ |
0.5 mg single, oral dose: 0.5 mg route of administration: Oral experiment type: SINGLE co-administered: |
BROTIZOLAM plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED |
Doses
| Dose | Population | Adverse events |
|---|---|---|
1 mg 1 times / day multiple, oral Highest studied dose Dose: 1 mg, 1 times / day Route: oral Route: multiple Dose: 1 mg, 1 times / day Sources: |
healthy, ADULT Health Status: healthy Age Group: ADULT Sex: unknown Food Status: UNKNOWN Sources: |
|
17.5 g single, oral Overdose |
healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
Other AEs: Death... |
3 mg single, oral Highest studied dose |
healthy Health Status: healthy Sex: unknown Food Status: UNKNOWN Sources: |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Death | grade 5 | 17.5 g single, oral Overdose |
healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Development of a list of potentially inappropriate drugs for the korean elderly using the delphi method. | 2010-12 |
|
| Comparisons of two different doses of fentanyl for procedural analgesia during epidural catheter placement: a double-blind prospective, randomized, placebo-controlled study. | 2010-12 |
|
| Unusual intracranial stab wounds inflicted with metal tent stakes for a case involving a family murder suicide. | 2010-10-10 |
|
| 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. | 2010-07-29 |
|
| Dose-dependent hemodynamic effects of propofol induction following brotizolam premedication in hypertensive patients taking angiotensin-converting enzyme inhibitors. | 2010-05 |
|
| Impaired prefrontal hemodynamic maturation in autism and unaffected siblings. | 2009-09-03 |
|
| The impact of age on the hypnotic effects of eszopiclone and zolpidem in the guinea pig. | 2009-07 |
|
| Paradoxical reactions to hypnotic agents in adolescents with free-running disorder. | 2009-06 |
|
| 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. | 2009-04 |
|
| The benzodiazepine brotizolam reduces fear in calves exposed to a novel object test. | 2009-02-16 |
|
| Non-ST Elevation Myocardial Infraction after High Dose Intravenous Immunoglobulin Infusion. | 2009 |
|
| Influence of serotonergic/noradrenergic gene polymorphisms on nausea and sweating induced by milnacipran in the treatment of depression. | 2009 |
|
| Differential clinical effects of fluvoxamine by the effect of age in Japanese female major depressive patients. | 2009 |
|
| Effect of Withania somnifera on Sleep-Wake Cycle in Sleep-Disturbed Rats: Possible GABAergic Mechanism. | 2008-11 |
|
| Juvenile stress-induced alteration of maturation of the GABAA receptor alpha subunit in the rat. | 2008-11 |
|
| Behavioral pharmacological properties after recovery from the loss of righting reflex induced by benzodiazepine receptor agonists in mice. | 2008-10 |
|
| Benzodiazepine metabolism: an analytical perspective. | 2008-10 |
|
| Evaluation of anxiolytic-like effects of some short-acting benzodiazepine hypnotics in mice. | 2008-07 |
|
| Absence status associated with focal activity and polydipsia-induced hyponatremia. | 2008-04 |
|
| Preliminary effects of pagoclone, a partial GABA(A) agonist, on neuropsychological performance. | 2008-02 |
|
| Case report: a case of intractable Meniere's disease treated with autogenic training. | 2008-01-25 |
|
| [Comparative study of drug efficacy and drug additives between generic drugs and original drugs]. | 2007-12 |
|
| Up-regulation of L-type high voltage-gated calcium channel subunits by sustained exposure to 1,4- and 1,5-benzodiazepines in cerebrocortical neurons. | 2007-12 |
|
| Sustained inhibition of brotizolam induced anterograde amnesia by norharmane and retrograde amnesia by L-glutamic acid in mice. | 2007-08-22 |
|
| High plasma concentrations of paroxetine impede clinical response in patients with panic disorder. | 2007-02 |
|
| Effects of quazepam as a preoperative night hypnotic: comparison with brotizolam. | 2007 |
|
| Potentiation of ethanol in spatial memory deficits induced by some benzodiazepines. | 2006-08 |
|
| Rifampicin markedly decreases plasma concentration and hypnotic effect of brotizolam. | 2006-06 |
|
| Effect of zolpidem on sleep architecture and its next-morning residual effect in insomniac patients: a randomized crossover comparative study with brotizolam. | 2006-01 |
|
| [Actigraphic assessment of the effects of hypnotics on the night before surgery in relation with the severity of surgery]. | 2005-11 |
|
| Diagnostic performance of Triage for benzodiazepines: urine analysis of the dose of therapeutic cases. | 2005-09 |
|
| Inhibition of the metabolism of brotizolam by erythromycin in humans: in vivo evidence for the involvement of CYP3A4 in brotizolam metabolism. | 2005-08 |
|
| Improvement of dry mouth by replacing paroxetine with fluvoxamine. | 2005-03 |
|
| Quantitative analysis of 33 benzodiazepines, metabolites and benzodiazepine-like substances in whole blood by liquid chromatography-(tandem) mass spectrometry. | 2004-11-05 |
|
| Effect of itraconazole on the pharmacokinetics and pharmacodynamics of a single oral dose of brotizolam. | 2004-11 |
|
| 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. | 2004-08 |
|
| Electroencephalographic properties of zaleplon, a non-benzodiazepine sedative/hypnotic, in rats. | 2004-03 |
|
| Zopiclone, but not brotizolam, impairs memory storage during sleep. | 2003-10 |
|
| CAP variables and arousals as sleep electroencephalogram markers for primary insomnia. | 2003-09 |
|
| Role of platelet activating factor in triazolobenzodiazepines-induced retrograde amnesia. | 2003-06-16 |
|
| Effects of short-acting hypnotics on sleep latency in rats placed on grid suspended over water. | 2003-01-24 |
|
| [Case of prolonged recovery from serotonin syndrome caused by paroxetine]. | 2003 |
|
| [Investigations of poisonings with benzodiazepine derivatives mixtures by thin-layer chromatography]. | 2003 |
|
| [Cytochrome P450 3A4 and Benzodiazepines]. | 2003 |
|
| Study of nocturnal sleep and the carryover effects of triazolam and brotizolam using neurophysiological and subjective methods. | 2003 |
|
| [Perioperative management for nephrectomy using combined spinal-epidural anesthesia with sedation in a patient with cerebral palsy under maintenance hemodialysis]. | 2002-11 |
|
| Evaluation of three ancillary treatments in the management of equine grass sickness. | 2002-09-28 |
|
| The flunitrazepam abuse prevention program at a general hospital in Taiwan: a descriptive study. | 2002-08 |
|
| The study of polysomnography and sleepiness the morning after administration of triazolam and brotizolam. | 2002-06 |
|
| Comparative pharmacokinetics of brotizolam and triazolam in healthy subjects. | 1983 |
Patents
Sample Use Guides
for adults: one tablet (0.25mg of brotizolam) is orally administered once daily at bedtime
Route of Administration:
Oral
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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DTXSID0022692
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5XZM1R3DKF
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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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100000085858
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2451
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SUB05933MIG
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C020960
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57801-81-7
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DB09017
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409
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CHEMBL32479
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T-113
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ACTIVE MOIETY
