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 8429	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 1970

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 1461 OCT2 647

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
OCT2 648	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/19002438/ Page: 10.0	yes [IC50 60 uM]
P-gp 1650	inhibitor 3277 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
Medullary A1 noradrenergic neurones may mediate oxytocin release after noxious stimuli.	2001 Aug 8	11496137
Effect of flumazenil on GABAA receptors in isolated rat hippocampal neurons.	2002 Dec	12515312
Effect of phosphatidylserine content on the partition coefficients of diazepam and flurazepam between phosphatidylcholine-phosphatidylserine bilayer of small unilamellar vesicles and water studied by second derivative spectrophotometry.	2002 Mar	11911192
Ethanol-mediated inhibition of mitogen-activated protein kinase phosphorylation in mouse brain.	2002 Mar 29	11937092
Benzodiazepine binding studies on living cells: application of small ligands for fluorescence correlation spectroscopy.	2002 Nov	12530545
Square-wave voltammetric techniques for determination of psychoactive 1,4-benzodiazepine drugs.	2002 Nov	12458422
19F NMR spectrometric determination of the partition coefficients of some fluorinated psychotropic drugs between phosphatidylcholine bilayer vesicles and water.	2002 Nov 7	12408899
The continuing challenge of inappropriate prescribing in the elderly: an update of the evidence.	2002 Nov-Dec	12482007
Ventral tegmental area dopamine neurons mediate the shock sensitization of acoustic startle: a potential site of action for benzodiazepine anxiolytics.	2002 Oct	12369800
Chronic benzodiazepine administration alters hippocampal CA1 neuron excitability: NMDA receptor function and expression(1).	2002 Sep	12367605
Deletion of the alpha1 or beta2 subunit of GABAA receptors reduces actions of alcohol and other drugs.	2003 Jan	12490572
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	15171931
'Hypnotic' prescription patterns in a large managed-care population.	2004 Sep	15341891
Toxic epidermal necrolysis caused by flurazepam?	2005 Dec	16392434
Role of giant depolarizing potentials in shaping synaptic currents in the developing hippocampus.	2006	17725505
Actions of glutamate and ivermectin on the pharyngeal muscle of Ascaridia galli: a comparative study with Caenorhabditis elegans.	2006 Apr	16442540
Zolpidem modified-release in insomnia.	2007	19300582
Genomic and functional conservation of sedative-hypnotic targets in the zebrafish.	2007 Apr	17496723
GABA transient sets the susceptibility of mIPSCs to modulation by benzodiazepine receptor agonists in rat hippocampal neurons.	2007 Nov 15	17855751
Prevalence of contraindications to mefloquine use among USA military personnel deployed to Central Asia.	2008 Feb 11	18267019
Flurazepam inhibits the P-glycoprotein transport function: an insight to revert multidrug-resistance phenotype.	2008 Feb 26	18190907
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
Reduced benzodiazepine tolerance, but increased flumazenil-precipitated withdrawal in AMPA-receptor GluR-A subunit-deficient mice.	2009 Apr	19141300
An epigenetic intervention interacts with genetic strain differences to modulate the stress-induced reduction of flurazepam's antiseizure efficacy in the mouse.	2009 Jun	19189880

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 `Fri Dec 15 15:20:49 GMT 2023` Edited by `admin` on `Fri Dec 15 15:20:49 GMT 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