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

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
Lack of residual sedation following middle-of-the-night zaleplon administration in sleep maintenance insomnia.	2000 Jan-Feb	10682226
Derivative spectrophotometric method for determination of acidity constants of single step acid-base equilibria.	2001 Aug 30	18968381
Sensitive gas chromatographic--mass spectrometric screening of acetylated benzodiazepines.	2001 Feb 23	11263563
Carbon monoxide-mediated hippocampal injury.	2001 Jul 10	11445621
Copper-psychoactive drug complexes: a voltammetric approach to complexation by 1,4-benzodiazepines.	2002 Apr 15	11950210
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
Long term benzodiazepine use for insomnia in patients over the age of 60: discordance of patient and physician perceptions.	2002 May 8	12019038
Benzodiazepine binding studies on living cells: application of small ligands for fluorescence correlation spectroscopy.	2002 Nov	12530545
Ventral tegmental area dopamine neurons mediate the shock sensitization of acoustic startle: a potential site of action for benzodiazepine anxiolytics.	2002 Oct	12369800
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
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
'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
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
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
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
Quantification of benzodiazepines in whole blood and serum.	2006 Nov	16220317
Genomic and functional conservation of sedative-hypnotic targets in the zebrafish.	2007 Apr	17496723
Greater incidence of depression with hypnotic use than with placebo.	2007 Aug 21	17711589
Prevalence of contraindications to mefloquine use among USA military personnel deployed to Central Asia.	2008 Feb 11	18267019
Benzodiazepine-mediated structural changes in the multidrug transporter P-glycoprotein: an intrinsic fluorescence quenching analysis.	2008 Jun	18791834
Chronic benzodiazepine-induced reduction in GABA(A) receptor-mediated synaptic currents in hippocampal CA1 pyramidal neurons prevented by prior nimodipine injection.	2008 Nov 11	18805463
Association between risk factors for injurious falls and new benzodiazepine prescribing in elderly persons.	2009 Jan 6	19126237
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.

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