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

Details

Stereochemistry ACHIRAL
Molecular Formula C21H23ClFN3O
Molecular Weight 387.8789
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of FLURAZEPAM

SMILES

CCN(CC)CCN1c2ccc(cc2C(=NCC1=O)c3ccccc3F)Cl

InChI

InChIKey=SAADBVWGJQAEFS-UHFFFAOYSA-N
InChI=1S/C21H23ClFN3O/c1-3-25(4-2)11-12-26-19-10-9-15(22)13-17(19)21(24-14-20(26)27)16-7-5-6-8-18(16)23/h5-10,13H,3-4,11-12,14H2,1-2H3

HIDE SMILES / InChI

Molecular Formula C21H23ClFN3O
Molecular Weight 387.8789
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Flurazepam (known under the brand names Dalmane and Dalmadorm) is a drug which is a benzodiazepine derivative. It is a hypnotic agent which does not appear to decrease dream time as measured by rapid eye movements (REM). Furthermore, it decreases sleep latency and number of awakenings for a consequent increase in total sleep time. Flurazepam binds to an allosteric site on GABA-A receptors. Binding potentiates the action of GABA on GABA-A receptors by opening the chloride channel within the receptor, causing chloride influx and hyperpolarization. Flurazepam is useful for the treatment of insomnia characterized by difficulty in falling asleep, frequent nocturnal awakenings, and/or early morning awakening. Flurazepam can be used effectively in patients with recurring insomnia or poor sleeping habits, and in acute or chronic medical situations requiring restful sleep.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Flurazepam

Approved Use

Flurazepam hydrochloride is a hypnotic agent useful for the treatment of insomnia characterized by difficulty in falling asleep, frequent nocturnal awakenings, and/or early morning awakening. Flurazepam hydrochloride capsules can be used effectively in patients with recurring insomnia or poor sleeping habits, and in acute or chronic medical situations requiring restful sleep. Sleep laboratory studies have objectively determined that flurazepam hydrochloride capsules are effective for at least 28 consecutive nights of drug administration. Since insomnia is often transient and intermittent, short-term use is usually sufficient. Prolonged use of hypnotics is usually not indicated and should only be undertaken concomitantly with appropriate evaluation of the patient.

Launch Date

8.2944E9
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
8.6 ng/mL
15 mg single, oral
dose: 15 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
HYDROXYETHYL-FLURAZEPAM plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
14 ng/mL
15 mg single, oral
dose: 15 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
N-DESALKYLFLURAZEPAM plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
2.5 ng/mL
15 mg single, oral
dose: 15 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FLURAZEPAM ALDEHYDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
2.5 h
15 mg single, oral
dose: 15 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
HYDROXYETHYL-FLURAZEPAM plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
75 h
15 mg single, oral
dose: 15 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
N-DESALKYLFLURAZEPAM plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
2.5 h
15 mg single, oral
dose: 15 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FLURAZEPAM ALDEHYDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
30 mg 1 times / day multiple, oral
Highest studied dose
Dose: 30 mg, 1 times / day
Route: oral
Route: multiple
Dose: 30 mg, 1 times / day
Sources:
healthy
n = 18
Health Status: healthy
Sex: M
Population Size: 18
Sources:
Other AEs: Somnolence, Agitation...
Other AEs:
Somnolence (5 patients)
Agitation (1 patient)
Dizziness (1 patient)
Sources:
AEs

AEs

AESignificanceDosePopulation
Agitation 1 patient
30 mg 1 times / day multiple, oral
Highest studied dose
Dose: 30 mg, 1 times / day
Route: oral
Route: multiple
Dose: 30 mg, 1 times / day
Sources:
healthy
n = 18
Health Status: healthy
Sex: M
Population Size: 18
Sources:
Dizziness 1 patient
30 mg 1 times / day multiple, oral
Highest studied dose
Dose: 30 mg, 1 times / day
Route: oral
Route: multiple
Dose: 30 mg, 1 times / day
Sources:
healthy
n = 18
Health Status: healthy
Sex: M
Population Size: 18
Sources:
Somnolence 5 patients
30 mg 1 times / day multiple, oral
Highest studied dose
Dose: 30 mg, 1 times / day
Route: oral
Route: multiple
Dose: 30 mg, 1 times / day
Sources:
healthy
n = 18
Health Status: healthy
Sex: M
Population Size: 18
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer


Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
yes [IC50 60 uM]
yes [IC50 62.5 uM]
PubMed

PubMed

TitleDatePubMed
The use of flurazepam (dalmane) as a substitute for barbiturates and methaqualone/diphenhydramine (mandrax) in general practice.
1976
Effect of flumazenil on GABAA receptors in isolated rat hippocampal neurons.
2002 Dec
Benzodiazepine binding studies on living cells: application of small ligands for fluorescence correlation spectroscopy.
2002 Nov
Square-wave voltammetric techniques for determination of psychoactive 1,4-benzodiazepine drugs.
2002 Nov
19F NMR spectrometric determination of the partition coefficients of some fluorinated psychotropic drugs between phosphatidylcholine bilayer vesicles and water.
2002 Nov 7
The continuing challenge of inappropriate prescribing in the elderly: an update of the evidence.
2002 Nov-Dec
Ventral tegmental area dopamine neurons mediate the shock sensitization of acoustic startle: a potential site of action for benzodiazepine anxiolytics.
2002 Oct
Chronic benzodiazepine administration alters hippocampal CA1 neuron excitability: NMDA receptor function and expression(1).
2002 Sep
Behavioral and hypnotic treatments for insomnia subtypes.
2003
Effects of benzodiazepines on frog ERG.
2003 Apr
A study into the rate of incorporation of eight benzodiazepines into rat hair.
2003 Apr 23
Effects of itraconazole on the plasma kinetics of quazepam and its two active metabolites after a single oral dose of the drug.
2003 Aug
H3 agonist immepip markedly reduces cortical histamine release, but only weakly promotes sleep in the rat.
2003 Aug
Deletion of the alpha1 or beta2 subunit of GABAA receptors reduces actions of alcohol and other drugs.
2003 Jan
Role of protein kinase A in GABAA receptor dysfunction in CA1 pyramidal cells following chronic benzodiazepine treatment.
2003 May
Pharmacokinetics and drug interactions of the sedative hypnotics.
2003 Winter
Residual effects of hypnotics: epidemiology and clinical implications.
2004
[Diagnostics and treatment of insomnia with concomitant arterial hypertension. Use of somnol as an adjuvant remedy].
2004 Apr-May
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
Quetiapine in hospitalized patients with schizophrenia refractory to treatment with first-generation antipsychotics: a 4-week, flexible-dose, single-blind, exploratory, pilot trial.
2004 Aug 1
Abolition of zolpidem sensitivity in mice with a point mutation in the GABAA receptor gamma2 subunit.
2004 Jul
Validated semiquantitative/quantitative screening of 51 drugs in whole blood as silylated derivatives by gas chromatography-selected ion monitoring mass spectrometry and gas chromatography electron capture detection.
2004 Jul 5
Transient plasticity of hippocampal CA1 neuron glutamate receptors contributes to benzodiazepine withdrawal-anxiety.
2004 Nov
The characterisation of selected drugs with amine-containing side chains using electrospray ionisation and ion trap mass spectrometry and their determination by HPLC-ESI-MS.
2004 Nov 15
A randomized controlled open trial of population-based disease and case management in a Medicare Plus Choice health maintenance organization.
2004 Oct
Presynaptic source of quantal size variability at GABAergic synapses in rat hippocampal neurons in culture.
2004 Oct
Clustering of extrasynaptic GABA(A) receptors modulates tonic inhibition in cultured hippocampal neurons.
2004 Oct 29
'Hypnotic' prescription patterns in a large managed-care population.
2004 Sep
Relative abuse liability of hypnotic drugs: a conceptual framework and algorithm for differentiating among compounds.
2005
Risk and benefit of drug use during pregnancy.
2005
Benzodiazepine modulation of partial agonist efficacy and spontaneously active GABA(A) receptors supports an allosteric model of modulation.
2005 Aug
Safety and tolerability of oral antifungal agents in the treatment of fungal nail disease: a proven reality.
2005 Dec
Toxic epidermal necrolysis caused by flurazepam?
2005 Dec
A 5-year prospective assessment of the risk associated with individual benzodiazepines and doses in new elderly users.
2005 Feb
Changes of brain neuropeptide Y and its receptors in rats with flurazepam tolerance and dependence.
2005 Nov
Role of giant depolarizing potentials in shaping synaptic currents in the developing hippocampus.
2006
Pharmacological properties of GABAA receptors containing gamma1 subunits.
2006 Feb
GABAergic signaling at mossy fiber synapses in neonatal rat hippocampus.
2006 Jan 11
Quantification of benzodiazepines in whole blood and serum.
2006 Nov
Noninvasive capnometry for continuous monitoring of mental status: a tale of 2 patients.
2006 Oct
Precipitation of long duration hypnic headaches after ACE inhibitor withdrawal.
2007 Nov
GABA transient sets the susceptibility of mIPSCs to modulation by benzodiazepine receptor agonists in rat hippocampal neurons.
2007 Nov 15
Determination of benzodiazepines in oral fluid using LC-MS-MS.
2007 Nov-Dec
Neuroanatomical pattern of mitochondrial complex I pathology varies between schizophrenia, bipolar disorder and major depression.
2008
Prevalence of contraindications to mefloquine use among USA military personnel deployed to Central Asia.
2008 Feb 11
Individually monitoring ligand-induced changes in the structure of the GABAA receptor at benzodiazepine binding site and non-binding-site interfaces.
2008 Jul
Benzodiazepine-mediated structural changes in the multidrug transporter P-glycoprotein: an intrinsic fluorescence quenching analysis.
2008 Jun
K+ channel TASK-1 knockout mice show enhanced sensitivities to ataxic and hypnotic effects of GABA(A) receptor ligands.
2008 Oct
Reduced benzodiazepine tolerance, but increased flumazenil-precipitated withdrawal in AMPA-receptor GluR-A subunit-deficient mice.
2009 Apr
Association between risk factors for injurious falls and new benzodiazepine prescribing in elderly persons.
2009 Jan 6
Patents

Sample Use Guides

Usual Adult Dose for Insomnia 15 mg orally once a day at bedtime for women and 15 or 30 mg orally once a day at bedtime for men Comments: -The 15 mg dose can be increased to 30 mg if necessary for efficacy. -The lowest effective dose should be used, since important adverse effects are dose related. -Dosage should be limited to 15 mg per day in elderly or debilitated patients.
Route of Administration: Oral
In Vitro Use Guide
Curator's Comment:: To investigate a possible mechanism of this synergistic interaction between propofol and benzodiazepines, the effect of propofol and flurazepam on GABAA receptor function was examined in Xenopus oocytes expressing recombinant alpha 1 beta 2 gamma 2L and alpha 2 beta 2 gamma 2L receptor constructs.
Potentiation of GABA receptor-activated current by low (1-10 uM) concentrations of propofol together with flurazepam (0.25-0.5 uM) was significantly greater than predicted by an additive response.
Substance Class Chemical
Created
by admin
on Sat Jun 26 03:40:24 UTC 2021
Edited
by admin
on Sat Jun 26 03:40:24 UTC 2021
Record UNII
IHP475989U
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
FLURAZEPAM
HSDB   INN   MART.   MI   VANDF   WHO-DD  
INN  
Official Name English
FLURAZEPAM [INN]
Common Name English
7-CHLORO-1-(2-(DIETHYLAMINO)ETHYL)-5-(O-FLUOROPHENYL)-1,3-DIHYDRO-2H-1,4-BENZODIAZEPIN-2-ONE
Common Name English
2H-1,4-BENZODIAZEPIN-2-ONE, 7-CHLORO-1-(2-(DIETHYLAMINO)ETHYL)-5-(2-FLUOROPHENYL)-1,3-DIHYDRO
Common Name English
FLURAZEPAM [MI]
Common Name English
FLURAZEPAM [JAN]
Common Name English
FLURAZEPAM [MART.]
Common Name English
FLURAZEPAM [WHO-DD]
Common Name English
INSUMIN
Brand Name English
FLURAZEPAM [HSDB]
Common Name English
FLURAZEPAM [VANDF]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C1012
Created by admin on Sat Jun 26 03:40:24 UTC 2021 , Edited by admin on Sat Jun 26 03:40:24 UTC 2021
NDF-RT N0000175694
Created by admin on Sat Jun 26 03:40:24 UTC 2021 , Edited by admin on Sat Jun 26 03:40:24 UTC 2021
NDF-RT N0000007542
Created by admin on Sat Jun 26 03:40:24 UTC 2021 , Edited by admin on Sat Jun 26 03:40:24 UTC 2021
WHO-VATC QN05CD01
Created by admin on Sat Jun 26 03:40:24 UTC 2021 , Edited by admin on Sat Jun 26 03:40:24 UTC 2021
WHO-ATC N05CD01
Created by admin on Sat Jun 26 03:40:24 UTC 2021 , Edited by admin on Sat Jun 26 03:40:24 UTC 2021
LIVERTOX 427
Created by admin on Sat Jun 26 03:40:24 UTC 2021 , Edited by admin on Sat Jun 26 03:40:24 UTC 2021
DEA NO. 2767
Created by admin on Sat Jun 26 03:40:24 UTC 2021 , Edited by admin on Sat Jun 26 03:40:24 UTC 2021
Code System Code Type Description
INN
2551
Created by admin on Sat Jun 26 03:40:24 UTC 2021 , Edited by admin on Sat Jun 26 03:40:24 UTC 2021
PRIMARY
ChEMBL
CHEMBL968
Created by admin on Sat Jun 26 03:40:24 UTC 2021 , Edited by admin on Sat Jun 26 03:40:24 UTC 2021
PRIMARY
EVMPD
SUB07744MIG
Created by admin on Sat Jun 26 03:40:24 UTC 2021 , Edited by admin on Sat Jun 26 03:40:24 UTC 2021
PRIMARY
RXCUI
4501
Created by admin on Sat Jun 26 03:40:24 UTC 2021 , Edited by admin on Sat Jun 26 03:40:24 UTC 2021
PRIMARY RxNorm
HSDB
3085
Created by admin on Sat Jun 26 03:40:24 UTC 2021 , Edited by admin on Sat Jun 26 03:40:24 UTC 2021
PRIMARY
DRUG BANK
DB00690
Created by admin on Sat Jun 26 03:40:24 UTC 2021 , Edited by admin on Sat Jun 26 03:40:24 UTC 2021
PRIMARY
FDA UNII
IHP475989U
Created by admin on Sat Jun 26 03:40:24 UTC 2021 , Edited by admin on Sat Jun 26 03:40:24 UTC 2021
PRIMARY
WIKIPEDIA
FLURAZEPAM
Created by admin on Sat Jun 26 03:40:24 UTC 2021 , Edited by admin on Sat Jun 26 03:40:24 UTC 2021
PRIMARY
NCI_THESAURUS
C62030
Created by admin on Sat Jun 26 03:40:24 UTC 2021 , Edited by admin on Sat Jun 26 03:40:24 UTC 2021
PRIMARY
IUPHAR
7188
Created by admin on Sat Jun 26 03:40:24 UTC 2021 , Edited by admin on Sat Jun 26 03:40:24 UTC 2021
PRIMARY
EPA CompTox
17617-23-1
Created by admin on Sat Jun 26 03:40:24 UTC 2021 , Edited by admin on Sat Jun 26 03:40:24 UTC 2021
PRIMARY
ECHA (EC/EINECS)
241-591-7
Created by admin on Sat Jun 26 03:40:24 UTC 2021 , Edited by admin on Sat Jun 26 03:40:24 UTC 2021
PRIMARY
MESH
D005479
Created by admin on Sat Jun 26 03:40:24 UTC 2021 , Edited by admin on Sat Jun 26 03:40:24 UTC 2021
PRIMARY
LACTMED
Flurazepam
Created by admin on Sat Jun 26 03:40:24 UTC 2021 , Edited by admin on Sat Jun 26 03:40:24 UTC 2021
PRIMARY
MERCK INDEX
M5498
Created by admin on Sat Jun 26 03:40:24 UTC 2021 , Edited by admin on Sat Jun 26 03:40:24 UTC 2021
PRIMARY Merck Index
CAS
17617-23-1
Created by admin on Sat Jun 26 03:40:24 UTC 2021 , Edited by admin on Sat Jun 26 03:40:24 UTC 2021
PRIMARY
PUBCHEM
3393
Created by admin on Sat Jun 26 03:40:24 UTC 2021 , Edited by admin on Sat Jun 26 03:40:24 UTC 2021
PRIMARY
DRUG CENTRAL
1218
Created by admin on Sat Jun 26 03:40:24 UTC 2021 , Edited by admin on Sat Jun 26 03:40:24 UTC 2021
PRIMARY
Related Record Type Details
BINDER->LIGAND
BINDING
TRANSPORTER -> INHIBITOR
Related Record Type Details
METABOLITE -> PARENT
URINE
METABOLITE -> PARENT
MAJOR
PLASMA
METABOLITE -> PARENT
PLASMA
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC