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Details

Stereochemistry ABSOLUTE
Molecular Formula C19H20BrN3O3
Molecular Weight 418.284
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of BRETAZENIL

SMILES

CC(C)(C)OC(=O)C1=C2[C@@H]3CCCN3C(=O)C4=C(Br)C=CC=C4N2C=N1

InChI

InChIKey=LWUDDYHYYNNIQI-ZDUSSCGKSA-N
InChI=1S/C19H20BrN3O3/c1-19(2,3)26-18(25)15-16-13-8-5-9-22(13)17(24)14-11(20)6-4-7-12(14)23(16)10-21-15/h4,6-7,10,13H,5,8-9H2,1-3H3/t13-/m0/s1

HIDE SMILES / InChI
Molecular Formula C19H20BrN3O3
Molecular Weight 418.284
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

Bretazenil (Ro 16-6028) is a partial agonist at the GABAA benzodiazepine site. It displayed anticonvulsive activity and was in phase III of a clinical trial in Switzerland to treat Anxiety disorders. But that study was discontinued.

Originator

Approval Year

Unknown
149124
Targets

Targets

Primary TargetPharmacologyConditionPotency
Partial Agonist
297
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase III
665
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
5 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/8799523/
0.5 mg single, sublingual
dose: 0.5 mg
route of administration: Sublingual
experiment type: SINGLE
co-administered:
BRETAZENIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
5.4 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/8799523/
0.5 mg single, sublingual
dose: 0.5 mg
route of administration: Sublingual
experiment type: SINGLE
co-administered: ALCOHOL
ALCOHOL
 BRETAZENIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
17.6 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/8799523/
0.5 mg single, sublingual
dose: 0.5 mg
route of administration: Sublingual
experiment type: SINGLE
co-administered:
BRETAZENIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
19.2 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/8799523/
0.5 mg single, sublingual
dose: 0.5 mg
route of administration: Sublingual
experiment type: SINGLE
co-administered: ALCOHOL
ALCOHOL
 BRETAZENIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
2.2 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/8799523/
0.5 mg single, sublingual
dose: 0.5 mg
route of administration: Sublingual
experiment type: SINGLE
co-administered:
BRETAZENIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
2.3 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/8799523/
0.5 mg single, sublingual
dose: 0.5 mg
route of administration: Sublingual
experiment type: SINGLE
co-administered: ALCOHOL
ALCOHOL
 BRETAZENIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
Doses

Doses

DosePopulationAdverse events​
18 mg 1 times / day multiple, oral
Studied dose
Dose: 18 mg, 1 times / day
Route: oral
Route: multiple
Dose: 18 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/8905533/
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/8905533/
Disc. AE: Tiredness, Insomnia...
Other AEs: Dizziness, Headache...
AEs leading to
discontinuation/dose reduction:
Tiredness (1.5%)
Insomnia (1.5%)
Other AEs:
Dizziness (6%)
Headache (3%)
Weight gain (1.5%)
Aggressiveness (1.5%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/8905533/
AEs

AEs

AESignificanceDosePopulation
Aggressiveness 1.5%
18 mg 1 times / day multiple, oral
Studied dose
Dose: 18 mg, 1 times / day
Route: oral
Route: multiple
Dose: 18 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/8905533/
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/8905533/
Weight gain 1.5%
18 mg 1 times / day multiple, oral
Studied dose
Dose: 18 mg, 1 times / day
Route: oral
Route: multiple
Dose: 18 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/8905533/
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/8905533/
Insomnia 1.5%
Disc. AE
18 mg 1 times / day multiple, oral
Studied dose
Dose: 18 mg, 1 times / day
Route: oral
Route: multiple
Dose: 18 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/8905533/
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/8905533/
Tiredness 1.5%
Disc. AE
18 mg 1 times / day multiple, oral
Studied dose
Dose: 18 mg, 1 times / day
Route: oral
Route: multiple
Dose: 18 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/8905533/
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/8905533/
Headache 3%
18 mg 1 times / day multiple, oral
Studied dose
Dose: 18 mg, 1 times / day
Route: oral
Route: multiple
Dose: 18 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/8905533/
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/8905533/
Dizziness 6%
18 mg 1 times / day multiple, oral
Studied dose
Dose: 18 mg, 1 times / day
Route: oral
Route: multiple
Dose: 18 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/8905533/
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/8905533/
PubMed

PubMed

TitleDatePubMed
Interneurons, GABAA currents, and subunit composition of the GABAA receptor in type I and type II cortical dysplasia.
2010-07
The point mutation gamma 2F77I changes the potency and efficacy of benzodiazepine site ligands in different GABAA receptor subtypes.
2010-06-25
Anticonvulsant, anxiolytic, and non-sedating actions of imidazenil and other imidazo-benzodiazepine carboxamide derivatives.
2010-06
Loss of GABAergic signaling by AgRP neurons to the parabrachial nucleus leads to starvation.
2009-06-26
Comparison of the novel subtype-selective GABAA receptor-positive allosteric modulator NS11394 [3'-[5-(1-hydroxy-1-methyl-ethyl)-benzoimidazol-1-yl]-biphenyl-2-carbonitrile] with diazepam, zolpidem, bretazenil, and gaboxadol in rat models of inflammatory and neuropathic pain.
2008-12
Varenicline in the treatment of tobacco dependence.
2008-04
Contribution of specific binding to the central benzodiazepine site to the brain concentrations of two novel benzodiazepine site ligands.
2007-09
Changes in relative potency among positive GABA(A) receptor modulators upon discontinuation of chronic benzodiazepine treatment in rhesus monkeys.
2007-05
Decreases in nestlet shredding of mice by serotonin uptake inhibitors: comparison with marble burying.
2006-03-20
Comparative cue generalization profiles of L-838, 417, SL651498, zolpidem, CL218,872, ocinaplon, bretazenil, zopiclone, and various benzodiazepines in chlordiazepoxide and zolpidem drug discrimination.
2006-03
Efficacy of bretazenil against cortical epileptic afterdischarges increases during early ontogeny in rats.
2006-02-21
Differential behavioral effects of low efficacy positive GABAA modulators in combination with benzodiazepines and a neuroactive steroid in rhesus monkeys.
2006-02
Pharmacological properties of GABAA receptors containing gamma1 subunits.
2006-02
Selective labelling of diazepam-insensitive GABAA receptors in vivo using [3H]Ro 15-4513.
2005-11
A comparison of chlordiazepoxide, bretazenil, L838,417 and zolpidem in a validated mouse Vogel conflict test.
2005-11
Comparison of the behavioral effects of bretazenil and flumazenil in triazolam-dependent and non-dependent baboons.
2005-09-05
The benzodiazepine binding site of GABA(A) receptors as a target for the development of novel anxiolytics.
2005-05
The mouse beam walking assay offers improved sensitivity over the mouse rotarod in determining motor coordination deficits induced by benzodiazepines.
2005-05
Anxioselective anxiolytics: can less be more?
2004-10-01
Agonist and antagonist effects of benzodiazepines on motor performance: influence of intrinsic efficacy and task difficulty.
2004-05
A rapid punishment procedure for detection of anxiolytic compounds in mice.
2004-02
Anxioselective compounds acting at the GABA(A) receptor benzodiazepine binding site.
2003-08
Mechanism-based pharmacokinetic/pharmacodynamic modeling of the electroencephalogram effects of GABAA receptor modulators: in vitro-in vivo correlations.
2003-01
Withdrawal from chronic intermittent ethanol treatment changes subunit composition, reduces synaptic function, and decreases behavioral responses to positive allosteric modulators of GABAA receptors.
2003-01
Neonatal development of the rat visual cortex: synaptic function of GABAA receptor alpha subunits.
2002-11-15
5-ethoxymethyl-7-fluoro-3-oxo-1,2,3,5-tetrahydrobenzo[4,5]imidazo[1,2a]pyridine-4-N-(2-fluorophenyl)carboxamide (RWJ-51204), a new nonbenzodiazepine anxiolytic.
2002-11
Pharmacological characterization of a novel cell line expressing human alpha(4)beta(3)delta GABA(A) receptors.
2002-08
Mechanism-based pharmacodynamic modeling of the interaction of midazolam, bretazenil, and zolpidem with ethanol.
2002-06
Role of the histidine residue at position 105 in the human alpha 5 containing GABA(A) receptor on the affinity and efficacy of benzodiazepine site ligands.
2002-01
Bretazenil, a benzodiazepine receptor partial agonist, as an adjunct in the prophylactic treatment of OP poisoning.
2001-12
Isobolographic analysis of chlordiazepoxide and triazolam combinations in squirrel monkeys discriminating triazolam.
2001-11
Ribozyme-mediated reduction of the GABA(A) receptor alpha1 subunit.
2001-08-15
Functional pharmacology of GABA(A) receptors containing the chicken brain gamma 4 subunit.
2001-05-04
Effect of alpha subunit on allosteric modulation of ion channel function in stably expressed human recombinant gamma-aminobutyric acid(A) receptors determined using (36)Cl ion flux.
2001-05
Enhanced anticonvulsant activity of neuroactive steroids in a rat model of catamenial epilepsy.
2001-03
Cloning of cDNAs encoding the human gamma-aminobutyric acid type A receptor alpha 6 subunit and characterization of the pharmacology of alpha 6-containing receptors.
1996-02
Changes in benzodiazepine-receptor activity modify morphine withdrawal syndrome in mice.
1992-08

Sample Use Guides

In Vivo Use Guide
Influence of oral administration of 1 mg bretazenil on the sleep EEG and the concomitant nocturnal secretion of cortisol, growth hormone and prolactin in ten healthy young men
Route of Administration: Oral
In Vitro Use Guide
Unknown
Substance Class Chemical
Created
by admin
on Mon Mar 31 18:24:03 GMT 2025
Edited
by admin
on Mon Mar 31 18:24:03 GMT 2025
Record UNII
OSZ0E9DGOJ
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
BRETAZENIL
INN   USAN  
USAN   INN  
Official Name English
RO 16-6028/000
Preferred Name English
bretazenil [INN]
Common Name English
RO-166028000
Code English
BRETAZENIL [USAN]
Common Name English
9H-IMIDAZO(1,5-A)PYRROLO(2,1-C)(1,4)BENZODIAZEPINE-1-CARBOXYLIC ACID, 8-BROMO-11,12,13,13A-TETRAHYDRO-9-OXO-, 1,1-DIMETHYLETHYL ESTER, (S)-
Common Name English
tert-Butyl (S)-8-bromo-11,12,13,13a-tetrahydro-9-oxo-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepine-1-carboxylate
Common Name English
RO-F61816-6028/000
Code English
Classification Tree Code System Code
NCI_THESAURUS C28197
Created by admin on Mon Mar 31 18:24:03 GMT 2025 , Edited by admin on Mon Mar 31 18:24:03 GMT 2025
NCI_THESAURUS C264
Created by admin on Mon Mar 31 18:24:03 GMT 2025 , Edited by admin on Mon Mar 31 18:24:03 GMT 2025
Code System Code Type Description
NCI_THESAURUS
C72111
Created by admin on Mon Mar 31 18:24:03 GMT 2025 , Edited by admin on Mon Mar 31 18:24:03 GMT 2025
PRIMARY
EPA CompTox
DTXSID6046266
Created by admin on Mon Mar 31 18:24:03 GMT 2025 , Edited by admin on Mon Mar 31 18:24:03 GMT 2025
PRIMARY
INN
6319
Created by admin on Mon Mar 31 18:24:03 GMT 2025 , Edited by admin on Mon Mar 31 18:24:03 GMT 2025
PRIMARY
USAN
DD-21
Created by admin on Mon Mar 31 18:24:03 GMT 2025 , Edited by admin on Mon Mar 31 18:24:03 GMT 2025
PRIMARY
MESH
C054626
Created by admin on Mon Mar 31 18:24:03 GMT 2025 , Edited by admin on Mon Mar 31 18:24:03 GMT 2025
PRIMARY
CAS
84379-13-5
Created by admin on Mon Mar 31 18:24:03 GMT 2025 , Edited by admin on Mon Mar 31 18:24:03 GMT 2025
PRIMARY
PUBCHEM
107926
Created by admin on Mon Mar 31 18:24:03 GMT 2025 , Edited by admin on Mon Mar 31 18:24:03 GMT 2025
PRIMARY
ChEMBL
CHEMBL366947
Created by admin on Mon Mar 31 18:24:03 GMT 2025 , Edited by admin on Mon Mar 31 18:24:03 GMT 2025
PRIMARY
WIKIPEDIA
BRETAZENIL
Created by admin on Mon Mar 31 18:24:03 GMT 2025 , Edited by admin on Mon Mar 31 18:24:03 GMT 2025
PRIMARY
SMS_ID
100000088643
Created by admin on Mon Mar 31 18:24:03 GMT 2025 , Edited by admin on Mon Mar 31 18:24:03 GMT 2025
PRIMARY
EVMPD
SUB05886MIG
Created by admin on Mon Mar 31 18:24:03 GMT 2025 , Edited by admin on Mon Mar 31 18:24:03 GMT 2025
PRIMARY
FDA UNII
OSZ0E9DGOJ
Created by admin on Mon Mar 31 18:24:03 GMT 2025 , Edited by admin on Mon Mar 31 18:24:03 GMT 2025
PRIMARY
Related Record Type Details
Structure of BRETAZENIL
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