U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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
Structure of BROTIZOLAM

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

HIDE SMILES / InChI

Description
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

Curator's Comment: CNS depressant Known to be CNS depressant in mice, rats and rabbits. Human data not available

Originator

Curator's Comment: # by a team led by T Nishiyama while working for Takeda Chemical Industries in 1976 in Japan

Approval Year

Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Lendormin

Approved Use

Unknown

Launch Date

1.19905924E12
PubMed

PubMed

TitleDatePubMed
Comparative pharmacokinetics of brotizolam and triazolam in healthy subjects.
1983
Actigraphic assessment of the preoperative hypnotic effects of brotizolam and zopiclone.
2002
The flunitrazepam abuse prevention program at a general hospital in Taiwan: a descriptive study.
2002 Aug
[Perioperative management for nephrectomy using combined spinal-epidural anesthesia with sedation in a patient with cerebral palsy under maintenance hemodialysis].
2002 Nov
Evaluation of three ancillary treatments in the management of equine grass sickness.
2002 Sep 28
[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
Effects of short-acting hypnotics on sleep latency in rats placed on grid suspended over water.
2003 Jan 24
Role of platelet activating factor in triazolobenzodiazepines-induced retrograde amnesia.
2003 Jun 16
CAP variables and arousals as sleep electroencephalogram markers for primary insomnia.
2003 Sep
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
Electroencephalographic properties of zaleplon, a non-benzodiazepine sedative/hypnotic, in rats.
2004 Mar
Effect of itraconazole on the pharmacokinetics and pharmacodynamics of a single oral dose of brotizolam.
2004 Nov
Quantitative analysis of 33 benzodiazepines, metabolites and benzodiazepine-like substances in whole blood by liquid chromatography-(tandem) mass spectrometry.
2004 Nov 5
Inhibition of the metabolism of brotizolam by erythromycin in humans: in vivo evidence for the involvement of CYP3A4 in brotizolam metabolism.
2005 Aug
Improvement of dry mouth by replacing paroxetine with fluvoxamine.
2005 Mar
[Actigraphic assessment of the effects of hypnotics on the night before surgery in relation with the severity of surgery].
2005 Nov
Diagnostic performance of Triage for benzodiazepines: urine analysis of the dose of therapeutic cases.
2005 Sep
Potentiation of ethanol in spatial memory deficits induced by some benzodiazepines.
2006 Aug
Effect of zolpidem on sleep architecture and its next-morning residual effect in insomniac patients: a randomized crossover comparative study with brotizolam.
2006 Jan
Rifampicin markedly decreases plasma concentration and hypnotic effect of brotizolam.
2006 Jun
Effects of quazepam as a preoperative night hypnotic: comparison with brotizolam.
2007
Sustained inhibition of brotizolam induced anterograde amnesia by norharmane and retrograde amnesia by L-glutamic acid in mice.
2007 Aug 22
[Comparative study of drug efficacy and drug additives between generic drugs and original drugs].
2007 Dec
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
High plasma concentrations of paroxetine impede clinical response in patients with panic disorder.
2007 Feb
Absence status associated with focal activity and polydipsia-induced hyponatremia.
2008 Apr
Preliminary effects of pagoclone, a partial GABA(A) agonist, on neuropsychological performance.
2008 Feb
Case report: a case of intractable Meniere's disease treated with autogenic training.
2008 Jan 25
Evaluation of anxiolytic-like effects of some short-acting benzodiazepine hypnotics in mice.
2008 Jul
Effect of Withania somnifera on Sleep-Wake Cycle in Sleep-Disturbed Rats: Possible GABAergic Mechanism.
2008 Nov
Juvenile stress-induced alteration of maturation of the GABAA receptor alpha subunit in the rat.
2008 Nov
Benzodiazepine metabolism: an analytical perspective.
2008 Oct
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
The benzodiazepine brotizolam reduces fear in calves exposed to a novel object test.
2009 Feb 16
Impaired prefrontal hemodynamic maturation in autism and unaffected siblings.
2009 Sep 3
Development of a list of potentially inappropriate drugs for the korean elderly using the delphi method.
2010 Dec
Comparisons of two different doses of fentanyl for procedural analgesia during epidural catheter placement: a double-blind prospective, randomized, placebo-controlled study.
2010 Dec
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
Patents

Patents

Sample Use Guides

for adults: one tablet (0.25mg of brotizolam) is orally administered once daily at bedtime
Route of Administration: Oral
In Vitro Use Guide
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.
Name Type Language
BROTIZOLAM
EP   INN   JAN   MART.   MI   USAN   WHO-DD  
INN   USAN  
Official Name English
SINTONAL
Brand Name English
WE 941
Code English
WE-941
Code English
MEDERANTIL
Brand Name English
BROTIZOLAM [MART.]
Common Name English
BROTIZOLAM [USAN]
Common Name English
Brotizolam [WHO-DD]
Common Name English
LENDORM
Brand Name English
2-BROMO-4-(2-CHLOROPHENYL)-9-METHYL-6H-THIENO(3,2-F)-S-TRIAZOLO(4,3-A)(1,4)DIAZEPINE
Systematic Name English
BROTIZOLAM [EP MONOGRAPH]
Common Name English
8-BROMO-6-(O-CHLOROPHENYL)-1-METHYL-4H-S-TRIAZOLO(3,4-C)THIENO(2,3-E)-1,4-DIAZEPINE
Common Name English
BROTIZOLAM [MI]
Common Name English
NIMBISAN
Brand Name English
WE-941-BS
Code English
LENDORMIN
Brand Name English
BROTIZOLAM [JAN]
Common Name English
2-Bromo-4-(O-chlorophenyl)-9-methyl-6H-thieno[3,2-f]-S-triazolo[4,3-a][1,4]diazepine
Common Name English
brotizolam [INN]
Common Name English
6H-THIENO(3,2-F)(1,2,4)TRIAZOLO(4,3-A)(1,4)DIAZEPINE, 2-BROMO-4-(2-CHLOROPHENYL)-9-METHYL-
Systematic Name English
Classification Tree Code System Code
WHO-ATC N05CD09
Created by admin on Fri Dec 15 15:18:45 UTC 2023 , Edited by admin on Fri Dec 15 15:18:45 UTC 2023
NCI_THESAURUS C1012
Created by admin on Fri Dec 15 15:18:45 UTC 2023 , Edited by admin on Fri Dec 15 15:18:45 UTC 2023
WHO-VATC QN05CD09
Created by admin on Fri Dec 15 15:18:45 UTC 2023 , Edited by admin on Fri Dec 15 15:18:45 UTC 2023
Code System Code Type Description
NCI_THESAURUS
C87057
Created by admin on Fri Dec 15 15:18:45 UTC 2023 , Edited by admin on Fri Dec 15 15:18:45 UTC 2023
PRIMARY
INN
4549
Created by admin on Fri Dec 15 15:18:45 UTC 2023 , Edited by admin on Fri Dec 15 15:18:45 UTC 2023
PRIMARY
EPA CompTox
DTXSID0022692
Created by admin on Fri Dec 15 15:18:45 UTC 2023 , Edited by admin on Fri Dec 15 15:18:45 UTC 2023
PRIMARY
FDA UNII
5XZM1R3DKF
Created by admin on Fri Dec 15 15:18:45 UTC 2023 , Edited by admin on Fri Dec 15 15:18:45 UTC 2023
PRIMARY
MERCK INDEX
m2729
Created by admin on Fri Dec 15 15:18:45 UTC 2023 , Edited by admin on Fri Dec 15 15:18:45 UTC 2023
PRIMARY Merck Index
ECHA (EC/EINECS)
260-964-5
Created by admin on Fri Dec 15 15:18:45 UTC 2023 , Edited by admin on Fri Dec 15 15:18:45 UTC 2023
PRIMARY
WIKIPEDIA
BROTIZOLAM
Created by admin on Fri Dec 15 15:18:45 UTC 2023 , Edited by admin on Fri Dec 15 15:18:45 UTC 2023
PRIMARY
RXCUI
19790
Created by admin on Fri Dec 15 15:18:45 UTC 2023 , Edited by admin on Fri Dec 15 15:18:45 UTC 2023
PRIMARY RxNorm
SMS_ID
100000085858
Created by admin on Fri Dec 15 15:18:45 UTC 2023 , Edited by admin on Fri Dec 15 15:18:45 UTC 2023
PRIMARY
PUBCHEM
2451
Created by admin on Fri Dec 15 15:18:45 UTC 2023 , Edited by admin on Fri Dec 15 15:18:45 UTC 2023
PRIMARY
EVMPD
SUB05933MIG
Created by admin on Fri Dec 15 15:18:45 UTC 2023 , Edited by admin on Fri Dec 15 15:18:45 UTC 2023
PRIMARY
MESH
C020960
Created by admin on Fri Dec 15 15:18:45 UTC 2023 , Edited by admin on Fri Dec 15 15:18:45 UTC 2023
PRIMARY
CAS
57801-81-7
Created by admin on Fri Dec 15 15:18:45 UTC 2023 , Edited by admin on Fri Dec 15 15:18:45 UTC 2023
PRIMARY
DRUG BANK
DB09017
Created by admin on Fri Dec 15 15:18:45 UTC 2023 , Edited by admin on Fri Dec 15 15:18:45 UTC 2023
PRIMARY
DRUG CENTRAL
409
Created by admin on Fri Dec 15 15:18:45 UTC 2023 , Edited by admin on Fri Dec 15 15:18:45 UTC 2023
PRIMARY
ChEMBL
CHEMBL32479
Created by admin on Fri Dec 15 15:18:45 UTC 2023 , Edited by admin on Fri Dec 15 15:18:45 UTC 2023
PRIMARY
USAN
T-113
Created by admin on Fri Dec 15 15:18:45 UTC 2023 , Edited by admin on Fri Dec 15 15:18:45 UTC 2023
PRIMARY