QUAZEPAM

Details

Stereochemistry	ACHIRAL
Molecular Formula	C17H11ClF4N2S
Molecular Weight	386.794
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

FC1=C(C=CC=C1)C2=NCC(=S)N(CC(F)(F)F)C3=C2C=C(Cl)C=C3

InChI

InChIKey=IKMPWMZBZSAONZ-UHFFFAOYSA-N

InChI=1S/C17H11ClF4N2S/c18-10-5-6-14-12(7-10)16(11-3-1-2-4-13(11)19)23-8-15(25)24(14)9-17(20,21)22/h1-7H,8-9H2

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018708s023lbl.pdf
Curator's Comment: description was created based on several sources, including: https://www.drugs.com/pro/quazepam.html | https://livertox.nlm.nih.gov/Quazepam.htm | https://www.ncbi.nlm.nih.gov/pubmed/1969151

Quazepam is indicated for the treatment of insomnia characterized by difficulty in falling asleep, frequent nocturnal awakenings, and/or early morning awakenings. Quazepam interact preferentially with the benzodiazepine-1 (BZ1) receptors. Most common adverse reactions (>1%): drowsiness, headache, fatigue, dizziness, dry mouth, dyspepsia. Downward of CAN depressant dose adjustment may be necessary due to additive effects.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
GABA-A receptor; anion channel 202 Target ID: CHEMBL2093872 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1969151 \| https://www.ncbi.nlm.nih.gov/pubmed/12420154	Positive Allosteric Modulator 179	101.0 nM [IC50]
Cytochrome P450 3A4 127 Target ID: CHEMBL340 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15801544	Substrate 661
Cytochrome P450 2C19 51 Target ID: CHEMBL3622 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15801544	Substrate 661
Cytochrome P450 2C9 50 Target ID: CHEMBL3397 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15801544	Substrate 661

Conditions

Condition	Modality	Targets	Highest Phase	Product
Insomnia 108 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018708s023lbl.pdf	Primary		Approved 8429	DORAL Approved Use QUAZEPAM® (quazepam) is indicated for the treatment of insomnia characterized by difficulty in falling asleep, frequent nocturnal awakenings, and/or early morning awakenings. The effectiveness of QUAZEPAM has been established in placebo-controlled clinical studies of 5 nights duration in acute and chronic insomnia. The sustained effectiveness of QUAZEPAM has been established in chronic insomnia in a sleep lab (polysomnographic) study of 28 nights duration. Because insomnia is often transient and intermittent, the prolonged administration of QUAZEPAM Tablets is generally not necessary or recommended. Since insomnia may be a symptom of several other disorders, the possibility that the complaint may be related to a condition for which there is a more specific treatment should be considered. QUAZEPAM, a gamma-aminobutyric (GABAA ) agonist, is indicated for the treatment of insomnia characterized by difficulty falling asleep, frequent nocturnal awakenings, and/or early morning awakenings. (1) Launch Date 1985

C_max

Value	Dose	Co-administered	Analyte	Population
28 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12680887	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:		QUAZEPAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
81.2 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12680887	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:		QUAZEPAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED

AUC

Value	Dose	Co-administered	Analyte	Population
291 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12680887	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:		QUAZEPAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
468 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12680887	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:		QUAZEPAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED

T_1/2

Value	Dose	Co-administered	Analyte	Population
14.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12680887	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:		QUAZEPAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
15.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12680887	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:		QUAZEPAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED

F_unbound

Value	Dose	Co-administered	Analyte	Population
5% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/018708s018lbl.pdf			QUAZEPAM plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
15 mg 1 times / day steady, oral Recommended Dose: 15 mg, 1 times / day Route: oral Route: steady Dose: 15 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6705450/	healthy, 19 - 39 years n = 11 Health Status: healthy Age Group: 19 - 39 years Sex: M Population Size: 11 Sources: https://pubmed.ncbi.nlm.nih.gov/6705450/	Sources: https://pubmed.ncbi.nlm.nih.gov/6705450/
30 mg 1 times / day steady, oral Highest studied dose Dose: 30 mg, 1 times / day Route: oral Route: steady Dose: 30 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6113910/	unhealthy, 22 -58 years n = 18 Health Status: unhealthy Condition: insomnia Age Group: 22 -58 years Sex: M+F Population Size: 18 Sources: https://pubmed.ncbi.nlm.nih.gov/6113910/	Sources: https://pubmed.ncbi.nlm.nih.gov/6113910/
20 mg single, oral Dose: 20 mg Route: oral Route: single Dose: 20 mg Sources: https://pubmed.ncbi.nlm.nih.gov/15385836/	healthy, 30.6 years n = 20 Health Status: healthy Age Group: 30.6 years Sex: M+F Population Size: 20 Sources: https://pubmed.ncbi.nlm.nih.gov/15385836/	Sources: https://pubmed.ncbi.nlm.nih.gov/15385836/
15 mg 1 times / day steady, oral Recommended Dose: 15 mg, 1 times / day Route: oral Route: steady Dose: 15 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018708s023lbl.pdf	unhealthy, adult n = 267 Health Status: unhealthy Condition: insomnia Age Group: adult Sex: unknown Population Size: 267 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018708s023lbl.pdf	Other AEs: Drowsiness, Headache... Other AEs: Drowsiness (12%) Headache (5%) Fatigue (2%) Dizziness (2%) Dry mouth (2%) Dyspepsia (1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018708s023lbl.pdf

AEs

AE	Significance	Dose	Population
Dyspepsia	1%	15 mg 1 times / day steady, oral Recommended Dose: 15 mg, 1 times / day Route: oral Route: steady Dose: 15 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018708s023lbl.pdf	unhealthy, adult n = 267 Health Status: unhealthy Condition: insomnia Age Group: adult Sex: unknown Population Size: 267 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018708s023lbl.pdf
Drowsiness	12%	15 mg 1 times / day steady, oral Recommended Dose: 15 mg, 1 times / day Route: oral Route: steady Dose: 15 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018708s023lbl.pdf	unhealthy, adult n = 267 Health Status: unhealthy Condition: insomnia Age Group: adult Sex: unknown Population Size: 267 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018708s023lbl.pdf
Dizziness	2%	15 mg 1 times / day steady, oral Recommended Dose: 15 mg, 1 times / day Route: oral Route: steady Dose: 15 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018708s023lbl.pdf	unhealthy, adult n = 267 Health Status: unhealthy Condition: insomnia Age Group: adult Sex: unknown Population Size: 267 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018708s023lbl.pdf
Dry mouth	2%	15 mg 1 times / day steady, oral Recommended Dose: 15 mg, 1 times / day Route: oral Route: steady Dose: 15 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018708s023lbl.pdf	unhealthy, adult n = 267 Health Status: unhealthy Condition: insomnia Age Group: adult Sex: unknown Population Size: 267 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018708s023lbl.pdf
Fatigue	2%	15 mg 1 times / day steady, oral Recommended Dose: 15 mg, 1 times / day Route: oral Route: steady Dose: 15 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018708s023lbl.pdf	unhealthy, adult n = 267 Health Status: unhealthy Condition: insomnia Age Group: adult Sex: unknown Population Size: 267 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018708s023lbl.pdf
Headache	5%	15 mg 1 times / day steady, oral Recommended Dose: 15 mg, 1 times / day Route: oral Route: steady Dose: 15 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018708s023lbl.pdf	unhealthy, adult n = 267 Health Status: unhealthy Condition: insomnia Age Group: adult Sex: unknown Population Size: 267 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018708s023lbl.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737	substrate 1037

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2B6 810 CYP2C8 911 CYP2E1 882	CYP2C19 991

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/018708s018lbl.pdf#page=2; https://patentimages.storage.googleapis.com/f0/4e/2b/bb4627286b330a/US7608616.pdf Page: 2.0	likely	likely (co-administration study) Comment: mechanism based inhibition; Increased plasma concentrations of drugs that are substrates of CYP2B6 may result if coadministered with DORAL; Bupropion (a CYP2B6 substrate): Co-administration of a single dose of 150 mg Bupropion Hydrochloride XL with steady state quazepam did not significantly affect the AUC and Cmax of bupropion or its primary metabolite, hydroxybupropion Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/018708s018lbl.pdf#page=2; https://patentimages.storage.googleapis.com/f0/4e/2b/bb4627286b330a/US7608616.pdf Page: 2.0
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/018708s018lbl.pdf#page=2 Page: 2.0	no
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/018708s018lbl.pdf#page=2 Page: 2.0	no

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP3A4 1737	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15801544/; https://journals.lww.com/drug-monitoring/Abstract/2003/08000/Effects_of_Itraconazole_on_the_Plasma_Kinetics_of.10.aspx	major	no (co-administration study) Comment: Itraconazole treatment did not change the plasma kinetics of quazepam Sources: https://pubmed.ncbi.nlm.nih.gov/15801544/; https://journals.lww.com/drug-monitoring/Abstract/2003/08000/Effects_of_Itraconazole_on_the_Plasma_Kinetics_of.10.aspx
CYP2C19 991	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15801544/	minor
CYP2C9 1037	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15801544/	minor

Sourcing

Vendor/Aggregator	ID	URL
ABI Chem	AC1L1JE0
Alfa Chemistry	36735-22-5	https://www.alfa-chemistry.com/quazepam-civ-200-mg-cas-36735-22-5-item-291703.htm
Ambinter	Amb13889656	http://www.ambinter.com/reference/13889656
ChemTik	CTK6H1725
Chemieliva Pharmaceutical Co., Ltd	PBCM0529451
Clearsynth	CS-EB-01820	https://www.clearsynth.com/en/CSEB01820.html
Clearsynth	CS-ER-01811	https://www.clearsynth.com/en/CSER01811.html
Compound Cloud	4999
MuseChem	I008860	https://www.musechem.com/product/I008860.html
NovoSeek	4999
OChem	18282	http://www.ocheminc.com/index.php?act=psearch&pid=735Q225
PI Chemicals	PI-33655
Smolecule	S540818	http://www.smolecule.com/products/s540818
THE BioTek	bt-281199	https://www.thebiotek.com/product/inhibitors/bt-281199
Toronto Research Chemicals	KIT7213
ZINC	ZINC000000538266	http://zinc15.docking.org/substances/ZINC000000538266
iChemical	EBD23735	http://www.ichemical.com/chemicals/cas-36735-22-5
mcule	MCULE-9166809561

PubMed

Title	Date	PubMed
Bidirectional effects of beta-carbolines in reflex epilepsy.	1987 Sep	3119161
Quazepam versus triazolam in patients with sleep disorders: a double-blind study.	1993	7901174
Feasibility of an every-other-night regimen in insomniac patients: subjective hypnotic effectiveness of quazepam, triazolam, and placebo.	1993 Jan	8428895
Effect of dietary fat content in meals on pharmacokinetics of quazepam.	2002 Dec	12463728
Interaction study between fluvoxamine and quazepam.	2003 Dec	14615476
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
[Pharmacological profiles of benzodiazepinergic hypnotics and correlations with receptor subtypes].	2005 Jun	16045197
Sleep maintenance insomnia: strengths and weaknesses of current pharmacologic therapies.	2006 Jan-Mar	16517453
Effects of genetic polymorphism of cytochrome P450 enzymes on the pharmacokinetics of benzodiazepines.	2007 Aug	17635335
Indiplon in the treatment of sleep disorders.	2007 Dec	19300612
Community-based randomised controlled trial evaluating falls and osteoporosis risk management strategies.	2008 Nov 4	18983670
Diagnosis and treatment of chronic insomnia.	2010 Apr	20814491
Neuronal network pharmacodynamics of GABAergic modulation in the human cortex determined using pharmaco-magnetoencephalography.	2010 Apr	19937723
Development of a list of potentially inappropriate drugs for the korean elderly using the delphi method.	2010 Dec	21818443

Patents

Sample Use Guides

In Vivo Use Guide

Recommended initial dose is 7.5 mg

Route of Administration: Oral

In Vitro Use Guide

IC50 values obtained with quazepam as the competing ligand were 101 nM in cortex and 258 nM in rat cerebellum.

Name

Type

Language

QUAZEPAM

Official Name

English

QUAZEPAM [USP MONOGRAPH]

Common Name

English

QUAZEPAM CIV [USP-RS]

Common Name

English

7-Chloro-5-(O-fluorophenyl)-1,3-dihydro-1-(2,2,2-trifluoroethyl)-2H-1,4-benzodiazepine-2-thione

Common Name

English

2H-1,4-BENZODIAZEPINE-2-THIONE, 7-CHLORO-5-(2-FLUOROPHENYL)-1,3-DIHYDRO-1-(2,2,2-TRIFLUOROETHYL)-

Systematic Name

English

SCH-16134

Code

English

quazepam [INN]

Common Name

English

QUAZEPAM CIV

Common Name

English

Quazepam [WHO-DD]

Common Name

English

QUAZEPAM [MART.]

Common Name

English

DORAL

Common Name

English

QUAZEPAM [USAN]

Common Name

English

SCH 16134

Code

English

NSC-309702

Code

English

QUAZEPAM [JAN]

Common Name

English

QUAZEPAM [MI]

Common Name

English

QUAZEPAM [ORANGE BOOK]

Common Name

English

QUAZEPAM [VANDF]

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000175694