FLURAZEPAM

First approved in 1970

Details

Stereochemistry	ACHIRAL
Molecular Formula	C21H23ClFN3O
Molecular Weight	387.878
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCN(CC)CCN1C2=C(C=C(Cl)C=C2)C(=NCC1=O)C3=C(F)C=CC=C3

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	387.878
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/016721s076lbl.pdf | https://www.drugs.com/pro/flurazepam.html

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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
GABA-A receptor; anion channel 202 Target ID: CHEMBL2093872 Sources: https://www.drugbank.ca/drugs/DB00690 \| https://www.ncbi.nlm.nih.gov/pubmed/6094209 \| https://www.ncbi.nlm.nih.gov/pubmed/2863335	Positive Allosteric Modulator 179

Conditions

Condition	Modality	Targets	Highest Phase	Product
Insomnia 108 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/016721s076lbl.pdf	Primary		Approved 8360	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

C_max

Value	Dose	Analyte	Population
8.6 ng/mL OTHER https://pdf.hres.ca/dpd_pm/00013427.PDF	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 OTHER https://pdf.hres.ca/dpd_pm/00013427.PDF	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 OTHER https://pdf.hres.ca/dpd_pm/00013427.PDF	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

T_1/2

Value	Dose	Analyte	Population
2.5 h OTHER https://pdf.hres.ca/dpd_pm/00013427.PDF	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 OTHER https://pdf.hres.ca/dpd_pm/00013427.PDF	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 OTHER https://pdf.hres.ca/dpd_pm/00013427.PDF	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

Dose	Population	Adverse 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: https://pubmed.ncbi.nlm.nih.gov/16702893/	healthy n = 18 Health Status: healthy Sex: M Population Size: 18 Sources: https://pubmed.ncbi.nlm.nih.gov/16702893/	Other AEs: Somnolence, Agitation... Other AEs: Somnolence (5 patients) Agitation (1 patient) Dizziness (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/16702893/

AEs

AE	Significance	Dose	Population
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: https://pubmed.ncbi.nlm.nih.gov/16702893/	healthy n = 18 Health Status: healthy Sex: M Population Size: 18 Sources: https://pubmed.ncbi.nlm.nih.gov/16702893/
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: https://pubmed.ncbi.nlm.nih.gov/16702893/	healthy n = 18 Health Status: healthy Sex: M Population Size: 18 Sources: https://pubmed.ncbi.nlm.nih.gov/16702893/
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: https://pubmed.ncbi.nlm.nih.gov/16702893/	healthy n = 18 Health Status: healthy Sex: M Population Size: 18 Sources: https://pubmed.ncbi.nlm.nih.gov/16702893/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1437 OCT2 638

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
OCT2 639	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/19002438/ Page: 10.0	yes [IC50 60 uM]
P-gp 1626	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/18190907/	yes [IC50 62.5 uM]

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:5128	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:5128
ZINC	ZINC000000537752	http://zinc15.docking.org/substances/ZINC000000537752
eMolecules	1986868	https://www.emolecules.com/cgi-bin/more?vid=1986868

PubMed

Title	Date	PubMed
The use of flurazepam (dalmane) as a substitute for barbiturates and methaqualone/diphenhydramine (mandrax) in general practice.	1976	18375
Determination of Clobazam, Clorazepate, Flurazepam and Flunitrazepam in pharmaceutical preparations.	2002 May 16	18968634
Behavioral and hypnotic treatments for insomnia subtypes.	2003	15600131
H3 agonist immepip markedly reduces cortical histamine release, but only weakly promotes sleep in the rat.	2003 Aug	12798672
Pharmacokinetics and drug interactions of the sedative hypnotics.	2003 Winter	14561946
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	15329838
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	15469204
Abolition of zolpidem sensitivity in mice with a point mutation in the GABAA receptor gamma2 subunit.	2004 Jul	15165831
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	15522519
A randomized controlled open trial of population-based disease and case management in a Medicare Plus Choice health maintenance organization.	2004 Oct	15670436
Presynaptic source of quantal size variability at GABAergic synapses in rat hippocampal neurons in culture.	2004 Oct	15380001
'Hypnotic' prescription patterns in a large managed-care population.	2004 Sep	15341891
Relative abuse liability of hypnotic drugs: a conceptual framework and algorithm for differentiating among compounds.	2005	16336040
Risk and benefit of drug use during pregnancy.	2005	16007261
Benzodiazepine modulation of partial agonist efficacy and spontaneously active GABA(A) receptors supports an allosteric model of modulation.	2005 Aug	15912137
Safety and tolerability of oral antifungal agents in the treatment of fungal nail disease: a proven reality.	2005 Dec	18360572
Toxic epidermal necrolysis caused by flurazepam?	2005 Dec	16392434
A 5-year prospective assessment of the risk associated with individual benzodiazepines and doses in new elderly users.	2005 Feb	15673346
Changes of brain neuropeptide Y and its receptors in rats with flurazepam tolerance and dependence.	2005 Nov	16225749
Role of giant depolarizing potentials in shaping synaptic currents in the developing hippocampus.	2006	17725505
Modeling cumulative dose and exposure duration provided insights regarding the associations between benzodiazepines and injuries.	2006 Apr	16549262
Actions of glutamate and ivermectin on the pharyngeal muscle of Ascaridia galli: a comparative study with Caenorhabditis elegans.	2006 Apr	16442540
Pharmacological properties of GABAA receptors containing gamma1 subunits.	2006 Feb	16272224
Anti-conflict effects of benzodiazepines in rhesus monkeys: relationship with therapeutic doses in humans and role of GABAA receptors.	2006 Jan	16378217
GABAergic signaling at mossy fiber synapses in neonatal rat hippocampus.	2006 Jan 11	16407558
Impact of epsilon and theta subunits on pharmacological properties of alpha3beta1 GABAA receptors expressed in Xenopus oocytes.	2006 Jan 13	16412217
Sleep maintenance insomnia: strengths and weaknesses of current pharmacologic therapies.	2006 Jan-Mar	16517453
A double-blind, placebo- and flurazepam-controlled investigation of the residual psychomotor and cognitive effects of modified release zolpidem in young healthy volunteers.	2006 Jun	16702893
Acute flurazepam intoxication: a case report.	2006 Mar	16501350
Quantification of benzodiazepines in whole blood and serum.	2006 Nov	16220317
Eating and weight related cognitions in people with Schizophrenia : a case control study.	2006 Oct 31	17076886
Zolpidem modified-release in insomnia.	2007	19300582
Eszopiclone: its use in the treatment of insomnia.	2007 Aug	19300573
Benzodiazepine withdrawal-induced glutamatergic plasticity involves up-regulation of GluR1-containing alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors in Hippocampal CA1 neurons.	2007 Aug	17510319
Greater incidence of depression with hypnotic use than with placebo.	2007 Aug 21	17711589
Benzodiazepine receptor agonists affect both binding and gating of recombinant alpha1beta2gamma2 gamma-aminobutyric acid-A receptors.	2007 May 28	17471066
Precipitation of long duration hypnic headaches after ACE inhibitor withdrawal.	2007 Nov	17965960
GABA transient sets the susceptibility of mIPSCs to modulation by benzodiazepine receptor agonists in rat hippocampal neurons.	2007 Nov 15	17855751
Methadone induced torsade de pointes in a patient receiving antiretroviral therapy.	2007 Nov-Dec	18277734
Benzodiazepine-induced hippocampal CA1 neuron alpha-amino-3-hydroxy-5-methylisoxasole-4-propionic acid (AMPA) receptor plasticity linked to severity of withdrawal anxiety: differential role of voltage-gated calcium channels and N-methyl-D-aspartic acid receptors.	2007 Sep	17762513
Prevalence of contraindications to mefloquine use among USA military personnel deployed to Central Asia.	2008 Feb 11	18267019
Individually monitoring ligand-induced changes in the structure of the GABAA receptor at benzodiazepine binding site and non-binding-site interfaces.	2008 Jul	18424553
Subchronic treatment with antiepileptic drugs modifies pentylenetetrazol-induced seizures in mice: Its correlation with benzodiazepine receptor binding.	2008 Jun	18830436
Benzodiazepine-mediated structural changes in the multidrug transporter P-glycoprotein: an intrinsic fluorescence quenching analysis.	2008 Jun	18791834
Structural mechanisms underlying benzodiazepine modulation of the GABA(A) receptor.	2008 Mar 26	18367615
Flurazepam effect on GABAergic currents depends on extracellular pH.	2008 May	18362897
K+ channel TASK-1 knockout mice show enhanced sensitivities to ataxic and hypnotic effects of GABA(A) receptor ligands.	2008 Oct	18660435
Reduced benzodiazepine tolerance, but increased flumazenil-precipitated withdrawal in AMPA-receptor GluR-A subunit-deficient mice.	2009 Apr	19141300
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	18937304
Towards a basic endoscopic evaluation of swallowing in acute stroke - identification of salient findings by the inexperienced examiner.	2009 Mar 10	19284543

Patents

Sample Use Guides

In Vivo Use Guide

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

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 `Wed Jul 05 22:51:29 UTC 2023` Edited by `admin` on `Wed Jul 05 22:51:29 UTC 2023`
Record UNII	IHP475989U
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

FLURAZEPAM

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

Flurazepam [WHO-DD]

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

INSUMIN

Brand Name

English

FLURAZEPAM [HSDB]

Common Name

English

FLURAZEPAM [VANDF]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1012