Identification
- Summary
Quazepam is a long-acting benzodiazepine used to manage insomnia.
- Brand Names
- Doral
- Generic Name
- Quazepam
- DrugBank Accession Number
- DB01589
- Background
Quazepam is a trifluoroethyl benzodiazepine derivative. It was first approved in the US in 1985 and is used as a hypnotic for the treatment of insomnia.6
It appears to be unique amongst other benzodiazepine derivatives in its relatively high affinity for sleep-promoting α1 subunit-containing GABAA receptors and low affinity for other receptors.5
- Type
- Small Molecule
- Groups
- Approved, Illicit
- Structure
Structure for Quazepam (DB01589)
- Weight
- Average: 386.794
Monoisotopic: 386.026759579 - Chemical Formula
- C17H11ClF4N2S
- Synonyms
- Quazepam
- Quazepamum
- External IDs
- SCH 16134
- SCH-16134
Pharmacology
- Indication
Quazepam is indicated for the treatment of insomnia characterized by difficulty falling asleep, frequent nocturnal awakenings, and/or early morning awakenings.6
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Insomnia •••••••••••• •••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Benzodiazepines, including quazepam, exert their sedative and anxiolytic effects by potentiating the effects of endogenous GABA, the primary inhibitory neurotransmitter in the central nervous system.3
- Mechanism of action
Like other benzodiazepines, quazepam likely exerts its effects by potentiating the effect of gamma-aminobutyric acid (GABA) on GABA(A) receptors, the main inhibitory neurotransmitter receptors in the mammalian brain.4 GABA(A) receptors are a component of GABA-gated ionotropic chloride channels that produce inhibitory postsynaptic potentials - following activation by GABA, the channel undergoes a conformational change that allows the passage of chloride ions through the channel. The inhibitory potentials produced by GABA neurotransmission play an integral role in the suppression and control of epileptiform nerve firing such as that seen in epilepsy, which makes the GABA system a desirable target in the treatment of epilepsy.
Benzodiazepines are positive allosteric modulators of GABA(A) function. They bind to the interface between alpha (α) and gamma (γ) subunits on the receptor, commonly referred to as the benzodiazepine binding site, and modulate the receptor such that its inhibitory response to GABA binding is dramatically increased.4
Target Actions Organism AGABA(A) Receptor positive allosteric modulatorHumans AGABA(A) Receptor Benzodiazepine Binding Site ligandHumans - Absorption
The half-life of absorption following oral administration is approximately 30 minutes.6 Peak plasma concentration (Cmax) is approximately 20 ng/mL and occurs around 2 hours following administration.6
- Volume of distribution
Not Available
- Protein binding
Quazepam and both of its major metabolites are >95% protein-bound in plasma.6
- Metabolism
Quazepam undergoes extensive hepatic metabolism, primarily via CYP3A4 and to a lesser extent via CYP2C9, CYP2C19, and FMO1.1 Quazepam is first metabolized to 2-oxoquazepam, which is then further metabolized to both N-desalkyl-2-oxoquazepam (norflurazepam) and 3-hydroxy-2-oxoquazepam.1,2 Both 2-oxoquazepam and N-desalkyl-2-oxoquazepam exert CNS depressant activity.6
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- Route of elimination
Over the course of five days following the administration of radiolabeled quazepam, approximately 31% of the administered dose appeared in the urine and 23% appeared in the feces.6 Unchanged drug appeared in only trace amounts in the urine.6
- Half-life
The mean elimination half-lives of both quazepam and 2-oxoquazepam is approximately 39 hours.6 The mean elimination half-life of N-desalkyl-2-oxoquazepam is approximately 73 hours.6
- Clearance
Not Available
- Adverse Effects
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Benzodiazepine overdose is typically characterized by central nervous system depression ranging from mild drowsiness to coma.6 Mild-to-moderate cases may involve relatively minor symptoms like drowsiness, dysarthria, confusion, and ataxia, while severe cases may lead to respiratory depression and coma. In rare cases, paradoxical disinhibitory reactions (e.g. agitation, violent behaviour, impulsivity) may occur.
The management of benzodiazepine overdose should involve general supportive measures as clinically indicated. Flumazenil is a benzodiazepine receptor antagonist which is indicated for the complete or partial reversal of benzodiazepine-induced sedation, although its appropriateness is highly dependent on the clinical status and history of the patient.6 The use of flumazenil can lead to withdrawal and significant adverse reactions (e.g. seizures), especially in the context of mixed overdoses and in long-term benzodiazepine users with an established physical dependency, and its use is contraindicated in patients using benzodiazepines for potentially life-threatening conditions (e.g. status epilepticus).6 If the decision is made to use flumazenil, it should be used as specified in its prescribing information and as an adjunct alongside general supportive management.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The risk or severity of CNS depression can be increased when Quazepam is combined with 1,2-Benzodiazepine. Abametapir The serum concentration of Quazepam can be increased when it is combined with Abametapir. Acetazolamide The risk or severity of CNS depression can be increased when Acetazolamide is combined with Quazepam. Acetophenazine The risk or severity of CNS depression can be increased when Acetophenazine is combined with Quazepam. Agomelatine The risk or severity of CNS depression can be increased when Quazepam is combined with Agomelatine. - Food Interactions
- Avoid alcohol. Ingesting alcohol may increase the drowsiness and CNS depression caused by quazepam.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- International/Other Brands
- Dormalin
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Doral Tablet 15 mg/1 Oral Physicians Total Care, Inc. 1994-03-02 2002-06-30 US 
Doral Tablet 15 mg/1 Oral Nuro Pharma, Inc. 1985-12-27 2014-12-18 US Doral Tablet 15 mg/1 Oral Galt Pharmaceuticals, LLC 2017-07-19 Not applicable US Doral Tablet 15 mg/1 Oral Questcor Pharmaceuticals, Inc. 1985-12-27 2013-06-20 US Quazepam Tablet 15 mg/1 Oral KLE 2, Inc. 2013-08-08 2015-10-30 US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Quazepam Tablet 15 mg/1 Oral Atland Pharmaceuticals, Llc 2018-03-20 Not applicable US
Categories
- ATC Codes
- N05CD10 — Quazepam
- Drug Categories
- Benzazepines
- Benzodiazepine hypnotics and sedatives
- Benzodiazepines and benzodiazepine derivatives
- Central Nervous System Agents
- Central Nervous System Depressants
- Cytochrome P-450 CYP2B6 Inhibitors
- Cytochrome P-450 CYP2B6 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2C19 Substrates
- Cytochrome P-450 CYP2C9 Substrates
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Heterocyclic Compounds, Fused-Ring
- Hypnotics and Sedatives
- Nervous System
- Psycholeptics
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as 1,4-benzodiazepines. These are organic compounds containing a benzene ring fused to a 1,4-azepine.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Benzodiazepines
- Sub Class
- 1,4-benzodiazepines
- Direct Parent
- 1,4-benzodiazepines
- Alternative Parents
- Fluorobenzenes / Aryl fluorides / Aryl chlorides / Thiolactams / Ketimines / Propargyl-type 1,3-dipolar organic compounds / Azacyclic compounds / Thiocarbonyl compounds / Organopnictogen compounds / Organofluorides show 3 more
- Substituents
- 1,4-benzodiazepine / Alkyl fluoride / Alkyl halide / Aromatic heteropolycyclic compound / Aryl chloride / Aryl fluoride / Aryl halide / Azacycle / Benzenoid / Fluorobenzene show 16 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- benzodiazepine (CHEBI:8694)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- JF8V0828ZI
- CAS number
- 36735-22-5
- InChI Key
- IKMPWMZBZSAONZ-UHFFFAOYSA-N
- InChI
- 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
- IUPAC Name
- 7-chloro-5-(2-fluorophenyl)-1-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-1,4-benzodiazepine-2-thione
- SMILES
- FC1=CC=CC=C1C1=NCC(=S)N(CC(F)(F)F)C2=C1C=C(Cl)C=C2
References
- General References
- Miura M, Ohkubo T: In vitro metabolism of quazepam in human liver and intestine and assessment of drug interactions. Xenobiotica. 2004 Nov-Dec;34(11-12):1001-11. [Article]
- Zampaglione N, Hilbert JM, Ning J, Chung M, Gural R, Symchowicz S: Disposition and metabolic fate of 14C-quazepam in man. Drug Metab Dispos. 1985 Jan-Feb;13(1):25-9. [Article]
- Griffin CE 3rd, Kaye AM, Bueno FR, Kaye AD: Benzodiazepine pharmacology and central nervous system-mediated effects. Ochsner J. 2013 Summer;13(2):214-23. [Article]
- Sigel E, Steinmann ME: Structure, function, and modulation of GABA(A) receptors. J Biol Chem. 2012 Nov 23;287(48):40224-31. doi: 10.1074/jbc.R112.386664. Epub 2012 Oct 4. [Article]
- Moniri NH: Reintroduction of quazepam: an update on comparative hypnotic and adverse effects. Int Clin Psychopharmacol. 2019 Nov;34(6):275-285. doi: 10.1097/YIC.0000000000000277. [Article]
- FDA Approved Drug Products: Doral (quazepam) tablets for oral use [Link]
- External Links
- Human Metabolome Database
- HMDB0015528
- KEGG Drug
- D00457
- KEGG Compound
- C07336
- PubChem Compound
- 4999
- PubChem Substance
- 46505952
- ChemSpider
- 4825
- 35185
- ChEBI
- 8694
- ChEMBL
- CHEMBL1200472
- ZINC
- ZINC000000538266
- Therapeutic Targets Database
- DAP000690
- PharmGKB
- PA164744373
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Quazepam
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Physicians Total Care Inc.
- Questcor
- Dosage Forms
Form Route Strength Tablet Oral 15 mg/1 Tablet Oral - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US7608616 No 2009-10-27 2028-06-03 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 137.5-139 °C PhysProp water solubility Insoluble https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/018708s029lbl.pdf logP 4.03 SANGSTER (1994) - Predicted Properties
Property Value Source Water Solubility 0.00231 mg/mL ALOGPS logP 4.76 ALOGPS logP 5.06 Chemaxon logS -5.2 ALOGPS pKa (Strongest Acidic) 18.93 Chemaxon pKa (Strongest Basic) 2.59 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 1 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 15.6 Å2 Chemaxon Rotatable Bond Count 3 Chemaxon Refractivity 93.47 m3·mol-1 Chemaxon Polarizability 33.99 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter Yes Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9385 Blood Brain Barrier + 0.9789 Caco-2 permeable + 0.5748 P-glycoprotein substrate Substrate 0.5341 P-glycoprotein inhibitor I Inhibitor 0.9324 P-glycoprotein inhibitor II Inhibitor 0.8253 Renal organic cation transporter Inhibitor 0.6883 CYP450 2C9 substrate Non-substrate 0.8255 CYP450 2D6 substrate Non-substrate 0.8135 CYP450 3A4 substrate Substrate 0.5133 CYP450 1A2 substrate Inhibitor 0.7023 CYP450 2C9 inhibitor Inhibitor 0.5757 CYP450 2D6 inhibitor Non-inhibitor 0.6337 CYP450 2C19 inhibitor Inhibitor 0.688 CYP450 3A4 inhibitor Inhibitor 0.7937 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.9484 Ames test Non AMES toxic 0.6683 Carcinogenicity Non-carcinogens 0.7273 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 1.9195 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.978 hERG inhibition (predictor II) Inhibitor 0.6396
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 176.2374232 predictedDarkChem Lite v0.1.0 [M-H]- 178.92126 predictedDeepCCS 1.0 (2019) [M+H]+ 176.8136232 predictedDarkChem Lite v0.1.0 [M+H]+ 181.27925 predictedDeepCCS 1.0 (2019) [M+Na]+ 176.7332232 predictedDarkChem Lite v0.1.0 [M+Na]+ 188.37138 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Positive allosteric modulator
- Curator comments
- The GABA(A) receptor is pentameric (i.e. comprising 5 subunit proteins) and therefore has a multitude of potential isoforms. The above target is a collection of all possible GABA(A) subunits that may participate in the formation of the pentameric receptor and is not meant to imply direct a drug-protein interaction for each individual subunit.
- General Function
- Inhibitory extracellular ligand-gated ion channel activity
- Specific Function
- Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine...
Components:
References
- Sigel E, Steinmann ME: Structure, function, and modulation of GABA(A) receptors. J Biol Chem. 2012 Nov 23;287(48):40224-31. doi: 10.1074/jbc.R112.386664. Epub 2012 Oct 4. [Article]
- Zhu S, Noviello CM, Teng J, Walsh RM Jr, Kim JJ, Hibbs RE: Structure of a human synaptic GABAA receptor. Nature. 2018 Jul;559(7712):67-72. doi: 10.1038/s41586-018-0255-3. Epub 2018 Jun 27. [Article]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Ligand
- Curator comments
- Benzodiazepines modulate GABA(A) function by binding at the interface between alpha (α) and gamma (γ) subunits. Of the 6 α-subunits, only 4 (α-1, -2, -3, and -5) participate in the formation of this binding site. The above target is a collection of all α- and γ-subunits that are known to participate in the formation of the benzodiazepine binding site.
- General Function
- Inhibitory extracellular ligand-gated ion channel activity
- Specific Function
- Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine...
Components:
References
- Sigel E, Steinmann ME: Structure, function, and modulation of GABA(A) receptors. J Biol Chem. 2012 Nov 23;287(48):40224-31. doi: 10.1074/jbc.R112.386664. Epub 2012 Oct 4. [Article]
- Zhu S, Noviello CM, Teng J, Walsh RM Jr, Kim JJ, Hibbs RE: Structure of a human synaptic GABAA receptor. Nature. 2018 Jul;559(7712):67-72. doi: 10.1038/s41586-018-0255-3. Epub 2018 Jun 27. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Sugimoto K, Araki N, Ohmori M, Harada K, Cui Y, Tsuruoka S, Kawaguchi A, Fujimura A: Interaction between grapefruit juice and hypnotic drugs: comparison of triazolam and quazepam. Eur J Clin Pharmacol. 2006 Mar;62(3):209-15. doi: 10.1007/s00228-005-0071-1. Epub 2006 Jan 17. [Article]
- Kawaguchi A, Ohmori M, Tsuruoka S, Nishiki K, Harada K, Miyamori I, Yano R, Nakamura T, Masada M, Fujimura A: Drug interaction between St John's Wort and quazepam. Br J Clin Pharmacol. 2004 Oct;58(4):403-10. doi: 10.1111/j.1365-2125.2004.02171.x. [Article]
- Miura M, Ohkubo T: In vitro metabolism of quazepam in human liver and intestine and assessment of drug interactions. Xenobiotica. 2004 Nov-Dec;34(11-12):1001-11. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
- Gene Name
- CYP2C19
- Uniprot ID
- P33261
- Uniprot Name
- Cytochrome P450 2C19
- Molecular Weight
- 55930.545 Da
References
- Miura M, Ohkubo T: In vitro metabolism of quazepam in human liver and intestine and assessment of drug interactions. Xenobiotica. 2004 Nov-Dec;34(11-12):1001-11. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- Sugimoto K, Araki N, Ohmori M, Harada K, Cui Y, Tsuruoka S, Kawaguchi A, Fujimura A: Interaction between grapefruit juice and hypnotic drugs: comparison of triazolam and quazepam. Eur J Clin Pharmacol. 2006 Mar;62(3):209-15. doi: 10.1007/s00228-005-0071-1. Epub 2006 Jan 17. [Article]
Drug created at August 29, 2007 15:30 / Updated at February 10, 2023 08:55