FLURAZEPAM MONOHYDROCHLORIDE

First approved in 1970

Details

Stereochemistry	ACHIRAL
Molecular Formula	C21H23ClFN3O.ClH
Molecular Weight	424.339
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of FLURAZEPAM MONOHYDROCHLORIDE

Structure Search

SMILES

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

InChI

InChIKey=PUGVROXLRUQCAF-UHFFFAOYSA-N

InChI=1S/C21H23ClFN3O.ClH/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;1H

HIDE SMILES / InChI

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count

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

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
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
New sorbent for HPTLC--FTIR in situ determination of impurities in flurazepam.	2001 Feb	11231113
Sensitive gas chromatographic--mass spectrometric screening of acetylated benzodiazepines.	2001 Feb 23	11263563
Selective enhancement of AMPA receptor-mediated function in hippocampal CA1 neurons from chronic benzodiazepine-treated rats.	2002 Jul	12213255
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
Effects of striatal injections of GABA(A) receptor agonists and antagonists in a genetic animal model of paroxysmal dystonia.	2002 May 17	12044793
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
Role of GABA(A) receptors in the ethanol-mediated inhibition of extracellular signal-regulated kinase.	2002 Sep 6	12223228
H3 agonist immepip markedly reduces cortical histamine release, but only weakly promotes sleep in the rat.	2003 Aug	12798672
Clustering of extrasynaptic GABA(A) receptors modulates tonic inhibition in cultured hippocampal neurons.	2004 Oct 29	15317810
Risk and benefit of drug use during pregnancy.	2005	16007261
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
Sleep maintenance insomnia: strengths and weaknesses of current pharmacologic therapies.	2006 Jan-Mar	16517453
A double-blind, placebo-controlled investigation of the residual psychomotor and cognitive effects of zolpidem-MR in healthy elderly volunteers.	2006 Nov	17061961
Zolpidem modified-release in insomnia.	2007	19300582
Genomic and functional conservation of sedative-hypnotic targets in the zebrafish.	2007 Apr	17496723
Eszopiclone: its use in the treatment of insomnia.	2007 Aug	19300573
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
Increased AMPA receptor GluR1 subunit incorporation in rat hippocampal CA1 synapses during benzodiazepine withdrawal.	2008 Dec 20	18924138
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
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
Association between risk factors for injurious falls and new benzodiazepine prescribing in elderly persons.	2009 Jan 6	19126237
Functional characterization of the human organic cation transporter 2 variant p.270Ala>Ser.	2009 Jun	19251820
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 `Fri Dec 15 18:59:45 GMT 2023` Edited by `admin` on `Fri Dec 15 18:59:45 GMT 2023`
Record UNII	7C4JH842IJ
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

FLURAZEPAM MONOHYDROCHLORIDE

Common Name

English

FLURAZEPAM MONOHYDROCHLORIDE [EP MONOGRAPH]

Common Name

English

FLURAZEPAM MONOHYDROCHLORIDE [MART.]

Common Name

English

2H-1,4-BENZODIAZEPIN-2-ONE, 7-CHLORO-1-(2-(DIETHYLAMINO)ETHYL)-5-(2-FLUOROPHENYL)-1,3-DIHYDRO-, MONOHYDROCHLORIDE

Common Name

English

2H-1,4-BENZODIAZEPIN-2-ONE, 7-CHLORO-1-(2-(DIETHYLAMINO)ETHYL)-5-(2-FLUOROPHENYL)-1,3-DIHYDRO-, HYDROCHLORIDE (1:1)

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1012