Cinolazepam

Identification

Summary

Cinolazepam is a benzodiazepine used to manage severe and debilitating forms of sleep disorders of various origins in adults.

Generic Name
Cinolazepam
DrugBank Accession Number
DB01594
Background

Cinolazepam is a benzodiazepine derivative with anxiolytic, anticonvulsant, sedative and skeletal muscle relaxant activity. It is not approved in Canada or America.

Type
Small Molecule
Groups
Experimental
Structure
Thumb
Weight
Average: 357.766
Monoisotopic: 357.068032587
Chemical Formula
C18H13ClFN3O2
Synonyms
  • 1-(2-cyanoethyl)-7-chloro-3-hydroxy-5-(2'-fluorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one
  • 7-chloro-5-(2-fluorophenyl)-2,3-dihydro-3-hydroxy-2-oxo-1H-1,4-benzodiazepine-1-propanenitrile
  • 7-chloro-5-(o-fluorophenyl)-2,3-dihydro-3-hydroxy-2-oxo-1H-1,4-benzodiazepine-1-propionitrile
  • Cinolazepam
  • Cinolazepamum
External IDs
  • OX 373
  • OX-373

Pharmacology

Indication

For the management of anxiety disorders or for the short-term relief of the symptoms of anxiety or anxiety associated with depressive symptoms.

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Cinolazepam is a benzodiazepine derivative with anxiolytic, anticonvulsant, sedative and skeletal muscle relaxant activity. It is not approved in Canada or America.

Mechanism of action

Cinolazepam binds to central benzodiazepine receptors which interact allosterically with GABA receptors. This potentiates the effects of the inhibitory neurotransmitter GABA, increasing the inhibition of the ascending reticular activating system and blocking the cortical and limbic arousal that occurs following stimulation of the reticular pathways.

TargetActionsOrganism
AGABA(A) Receptor
positive allosteric modulator
Humans
AGABA(A) Receptor Benzodiazepine Binding Site
ligand
Humans
Absorption

Bioavailability following oral administration is 90-100%.

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

Hepatic.

Route of elimination

Not Available

Half-life

9 hours

Clearance

Not Available

Adverse Effects
Adverseeffects
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Toxicity

The onset of impairment of consciousness is relatively rapid in benzodiazepine poisoning. Onset is more rapid following larger doses and with agents of shorter duration of action. The most common and initial symptom is somnolence. This may progress to coma Grade I or Grade II following very large ingestions.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
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.
DrugInteraction
1,2-BenzodiazepineThe risk or severity of adverse effects can be increased when Cinolazepam is combined with 1,2-Benzodiazepine.
AcetazolamideThe risk or severity of adverse effects can be increased when Acetazolamide is combined with Cinolazepam.
AcetophenazineThe risk or severity of adverse effects can be increased when Acetophenazine is combined with Cinolazepam.
AclidiniumCinolazepam may increase the central nervous system depressant (CNS depressant) activities of Aclidinium.
AgomelatineThe risk or severity of adverse effects can be increased when Cinolazepam is combined with Agomelatine.
AlfentanilThe risk or severity of adverse effects can be increased when Alfentanil is combined with Cinolazepam.
AlimemazineThe risk or severity of adverse effects can be increased when Alimemazine is combined with Cinolazepam.
AlmotriptanThe risk or severity of adverse effects can be increased when Almotriptan is combined with Cinolazepam.
AlosetronThe risk or severity of adverse effects can be increased when Alosetron is combined with Cinolazepam.
AlprazolamThe risk or severity of adverse effects can be increased when Alprazolam is combined with Cinolazepam.
Interactions
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Food Interactions
  • Avoid alcohol.
  • Limit caffeine intake.
  • Take with food.

Products

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International/Other Brands
Gerodorm

Categories

ATC Codes
N05CD13 — Cinolazepam
Drug Categories
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
Alpha amino acids and derivatives / Fluorobenzenes / Aryl chlorides / Aryl fluorides / Tertiary carboxylic acid amides / Ketimines / Lactams / Alkanolamines / Propargyl-type 1,3-dipolar organic compounds / Azacyclic compounds
show 7 more
Substituents
1,4-benzodiazepine / Alkanolamine / Alpha-amino acid or derivatives / Aromatic heteropolycyclic compound / Aryl chloride / Aryl fluoride / Aryl halide / Azacycle / Benzenoid / Carbonitrile
show 23 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
organochlorine compound, 1,4-benzodiazepinone (CHEBI:59514)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
68P0556B0U
CAS number
75696-02-5
InChI Key
XAXMYHMKTCNRRZ-UHFFFAOYSA-N
InChI
InChI=1S/C18H13ClFN3O2/c19-11-6-7-15-13(10-11)16(12-4-1-2-5-14(12)20)22-17(24)18(25)23(15)9-3-8-21/h1-2,4-7,10,17,24H,3,9H2
IUPAC Name
3-[7-chloro-5-(2-fluorophenyl)-3-hydroxy-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-1-yl]propanenitrile
SMILES
OC1N=C(C2=CC=CC=C2F)C2=C(C=CC(Cl)=C2)N(CCC#N)C1=O

References

General References
Not Available
Human Metabolome Database
HMDB0015533
KEGG Drug
D07328
PubChem Compound
3033621
PubChem Substance
46508803
ChemSpider
2298251
ChEBI
59514
ChEMBL
CHEMBL2104926
Therapeutic Targets Database
DAP001250
PharmGKB
PA164748034
Wikipedia
Cinolazepam

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
TabletOral40 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.012 mg/mLALOGPS
logP2.42ALOGPS
logP2.7ChemAxon
logS-4.5ALOGPS
pKa (Strongest Acidic)10.68ChemAxon
pKa (Strongest Basic)-2.5ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area76.69 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity90.99 m3·mol-1ChemAxon
Polarizability34.12 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9872
Blood Brain Barrier+0.9778
Caco-2 permeable+0.5712
P-glycoprotein substrateSubstrate0.5264
P-glycoprotein inhibitor IInhibitor0.7371
P-glycoprotein inhibitor IIInhibitor0.9286
Renal organic cation transporterInhibitor0.5421
CYP450 2C9 substrateNon-substrate0.6806
CYP450 2D6 substrateNon-substrate0.8239
CYP450 3A4 substrateSubstrate0.7105
CYP450 1A2 substrateInhibitor0.6771
CYP450 2C9 inhibitorInhibitor0.5139
CYP450 2D6 inhibitorNon-inhibitor0.8453
CYP450 2C19 inhibitorInhibitor0.5565
CYP450 3A4 inhibitorInhibitor0.6491
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6814
Ames testNon AMES toxic0.757
CarcinogenicityNon-carcinogens0.8621
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.0412 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9948
hERG inhibition (predictor II)Non-inhibitor0.5099
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Drugtargets2
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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
  1. 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]
  2. 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
  1. 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]
  2. 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]

Drug created on August 29, 2007 17:43 / Updated on May 05, 2021 20:30