Identification

Name
Cinolazepam
Accession Number
DB01594
Type
Small Molecule
Groups
Approved
Description

Cinolazepam is a benzodiazepine derivative. It possesses anxiolytic, anticonvulsant, sedative and skeletal muscle relaxant properties. Cinolazepam is not approved for sale in the United States or Canada.

Structure
Thumb
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
  • Cinolazepamum
International/Other Brands
Gerodorm
Categories
UNII
68P0556B0U
CAS number
75696-02-5
Weight
Average: 357.766
Monoisotopic: 357.068032587
Chemical Formula
C18H13ClFN3O2
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

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.

Structured Indications
Not Available
Pharmacodynamics

Cinolazepam is a drug which is a benzodiazepine derivative. It possesses anxiolytic, anticonvulsant, sedative and skeletal muscle relaxant properties. Cinolazepam is not approved for sale in the United States or Canada.

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
AGamma-aminobutyric acid receptor subunit alpha-1
potentiator
Human
AGamma-aminobutyric acid receptor subunit alpha-2
potentiator
Human
AGamma-aminobutyric acid receptor subunit alpha-3
potentiator
Human
AGamma-aminobutyric acid receptor subunit alpha-5
potentiator
Human
AGamma-aminobutyric acid receptor subunit gamma-1
potentiator
Human
AGamma-aminobutyric acid receptor subunit gamma-2
potentiator
Human
AGamma-aminobutyric acid receptor subunit gamma-3
potentiator
Human
AGamma-aminobutyric acid receptor subunit beta-1
potentiator
Human
AGamma-aminobutyric acid receptor subunit beta-2
potentiator
Human
AGamma-aminobutyric acid receptor subunit beta-3
potentiator
Human
AGamma-aminobutyric acid receptor subunit delta
potentiator
Human
AGamma-aminobutyric acid receptor subunit epsilon
potentiator
Human
AGamma-aminobutyric acid receptor subunit pi
potentiator
Human
AGamma-aminobutyric acid receptor subunit rho-1
potentiator
Human
AGamma-aminobutyric acid receptor subunit rho-2
potentiator
Human
AGamma-aminobutyric acid receptor subunit rho-3
potentiator
Human
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
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.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
  • Avoid alcohol.
  • Avoid excessive quantities of coffee or tea (Caffeine).
  • Take with food.

References

General References
Not Available
External Links
Human Metabolome Database
HMDB15533
PubChem Compound
3033621
PubChem Substance
46508803
ChemSpider
2298251
ChEBI
59514
ChEMBL
CHEMBL2104926
Therapeutic Targets Database
DAP001250
PharmGKB
PA164748034
Wikipedia
Cinolazepam
ATC Codes
N05CD13 — Cinolazepam

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
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

Taxonomy

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 / Alpha-amino acid or derivatives / Fluorobenzene / Halobenzene / Aryl chloride / Aryl fluoride / Aryl halide / Monocyclic benzene moiety / Benzenoid / Tertiary carboxylic acid amide
show 23 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
organochlorine compound, 1,4-benzodiazepinone (CHEBI:59514)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Potentiator
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...
Gene Name
GABRA1
Uniprot ID
P14867
Uniprot Name
Gamma-aminobutyric acid receptor subunit alpha-1
Molecular Weight
51801.395 Da
References
  1. Amin J, Brooks-Kayal A, Weiss DS: Two tyrosine residues on the alpha subunit are crucial for benzodiazepine binding and allosteric modulation of gamma-aminobutyric acidA receptors. Mol Pharmacol. 1997 May;51(5):833-41. [PubMed:9145922]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Potentiator
General Function
Inhibitory extracellular ligand-gated ion channel activity
Specific Function
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name
GABRA2
Uniprot ID
P47869
Uniprot Name
Gamma-aminobutyric acid receptor subunit alpha-2
Molecular Weight
51325.85 Da
References
  1. Walash MI, Belal F, Metwally ME, Hefnawy MM: A selective fluorimetric method for the determination of some 1,4-benzodiazepine drugs containing a hydroxyl group at C-3. J Pharm Biomed Anal. 1994 Nov;12(11):1417-23. [PubMed:7849137]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Potentiator
General Function
Inhibitory extracellular ligand-gated ion channel activity
Specific Function
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name
GABRA3
Uniprot ID
P34903
Uniprot Name
Gamma-aminobutyric acid receptor subunit alpha-3
Molecular Weight
55164.055 Da
References
  1. Walash MI, Belal F, Metwally ME, Hefnawy MM: A selective fluorimetric method for the determination of some 1,4-benzodiazepine drugs containing a hydroxyl group at C-3. J Pharm Biomed Anal. 1994 Nov;12(11):1417-23. [PubMed:7849137]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Potentiator
General Function
Transporter activity
Specific Function
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name
GABRA5
Uniprot ID
P31644
Uniprot Name
Gamma-aminobutyric acid receptor subunit alpha-5
Molecular Weight
52145.645 Da
References
  1. Walash MI, Belal F, Metwally ME, Hefnawy MM: A selective fluorimetric method for the determination of some 1,4-benzodiazepine drugs containing a hydroxyl group at C-3. J Pharm Biomed Anal. 1994 Nov;12(11):1417-23. [PubMed:7849137]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Potentiator
General Function
Inhibitory extracellular ligand-gated ion channel activity
Specific Function
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name
GABRG1
Uniprot ID
Q8N1C3
Uniprot Name
Gamma-aminobutyric acid receptor subunit gamma-1
Molecular Weight
53594.49 Da
References
  1. Walash MI, Belal F, Metwally ME, Hefnawy MM: A selective fluorimetric method for the determination of some 1,4-benzodiazepine drugs containing a hydroxyl group at C-3. J Pharm Biomed Anal. 1994 Nov;12(11):1417-23. [PubMed:7849137]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Potentiator
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...
Gene Name
GABRG2
Uniprot ID
P18507
Uniprot Name
Gamma-aminobutyric acid receptor subunit gamma-2
Molecular Weight
54161.78 Da
References
  1. Walash MI, Belal F, Metwally ME, Hefnawy MM: A selective fluorimetric method for the determination of some 1,4-benzodiazepine drugs containing a hydroxyl group at C-3. J Pharm Biomed Anal. 1994 Nov;12(11):1417-23. [PubMed:7849137]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Potentiator
General Function
Inhibitory extracellular ligand-gated ion channel activity
Specific Function
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name
GABRG3
Uniprot ID
Q99928
Uniprot Name
Gamma-aminobutyric acid receptor subunit gamma-3
Molecular Weight
54288.16 Da
References
  1. Walash MI, Belal F, Metwally ME, Hefnawy MM: A selective fluorimetric method for the determination of some 1,4-benzodiazepine drugs containing a hydroxyl group at C-3. J Pharm Biomed Anal. 1994 Nov;12(11):1417-23. [PubMed:7849137]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Potentiator
General Function
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...
Gene Name
GABRB1
Uniprot ID
P18505
Uniprot Name
Gamma-aminobutyric acid receptor subunit beta-1
Molecular Weight
54234.085 Da
References
  1. Walash MI, Belal F, Metwally ME, Hefnawy MM: A selective fluorimetric method for the determination of some 1,4-benzodiazepine drugs containing a hydroxyl group at C-3. J Pharm Biomed Anal. 1994 Nov;12(11):1417-23. [PubMed:7849137]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Potentiator
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...
Gene Name
GABRB2
Uniprot ID
P47870
Uniprot Name
Gamma-aminobutyric acid receptor subunit beta-2
Molecular Weight
59149.895 Da
References
  1. Walash MI, Belal F, Metwally ME, Hefnawy MM: A selective fluorimetric method for the determination of some 1,4-benzodiazepine drugs containing a hydroxyl group at C-3. J Pharm Biomed Anal. 1994 Nov;12(11):1417-23. [PubMed:7849137]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Potentiator
General Function
Gaba-gated chloride 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...
Gene Name
GABRB3
Uniprot ID
P28472
Uniprot Name
Gamma-aminobutyric acid receptor subunit beta-3
Molecular Weight
54115.04 Da
References
  1. Walash MI, Belal F, Metwally ME, Hefnawy MM: A selective fluorimetric method for the determination of some 1,4-benzodiazepine drugs containing a hydroxyl group at C-3. J Pharm Biomed Anal. 1994 Nov;12(11):1417-23. [PubMed:7849137]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Potentiator
General Function
Gaba-a receptor activity
Specific Function
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name
GABRD
Uniprot ID
O14764
Uniprot Name
Gamma-aminobutyric acid receptor subunit delta
Molecular Weight
50707.835 Da
References
  1. Walash MI, Belal F, Metwally ME, Hefnawy MM: A selective fluorimetric method for the determination of some 1,4-benzodiazepine drugs containing a hydroxyl group at C-3. J Pharm Biomed Anal. 1994 Nov;12(11):1417-23. [PubMed:7849137]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Potentiator
General Function
Inhibitory extracellular ligand-gated ion channel activity
Specific Function
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name
GABRE
Uniprot ID
P78334
Uniprot Name
Gamma-aminobutyric acid receptor subunit epsilon
Molecular Weight
57971.175 Da
References
  1. Walash MI, Belal F, Metwally ME, Hefnawy MM: A selective fluorimetric method for the determination of some 1,4-benzodiazepine drugs containing a hydroxyl group at C-3. J Pharm Biomed Anal. 1994 Nov;12(11):1417-23. [PubMed:7849137]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Potentiator
General Function
Gaba-a receptor activity
Specific Function
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel. In the ute...
Gene Name
GABRP
Uniprot ID
O00591
Uniprot Name
Gamma-aminobutyric acid receptor subunit pi
Molecular Weight
50639.735 Da
References
  1. Walash MI, Belal F, Metwally ME, Hefnawy MM: A selective fluorimetric method for the determination of some 1,4-benzodiazepine drugs containing a hydroxyl group at C-3. J Pharm Biomed Anal. 1994 Nov;12(11):1417-23. [PubMed:7849137]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Potentiator
General Function
Gaba-a receptor activity
Specific Function
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel. Rho-1 GABA...
Gene Name
GABRR1
Uniprot ID
P24046
Uniprot Name
Gamma-aminobutyric acid receptor subunit rho-1
Molecular Weight
55882.91 Da
References
  1. Walash MI, Belal F, Metwally ME, Hefnawy MM: A selective fluorimetric method for the determination of some 1,4-benzodiazepine drugs containing a hydroxyl group at C-3. J Pharm Biomed Anal. 1994 Nov;12(11):1417-23. [PubMed:7849137]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Potentiator
General Function
Gaba-a receptor activity
Specific Function
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel. Rho-2 GABA...
Gene Name
GABRR2
Uniprot ID
P28476
Uniprot Name
Gamma-aminobutyric acid receptor subunit rho-2
Molecular Weight
54150.41 Da
References
  1. Walash MI, Belal F, Metwally ME, Hefnawy MM: A selective fluorimetric method for the determination of some 1,4-benzodiazepine drugs containing a hydroxyl group at C-3. J Pharm Biomed Anal. 1994 Nov;12(11):1417-23. [PubMed:7849137]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Potentiator
General Function
Gaba-a receptor activity
Specific Function
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name
GABRR3
Uniprot ID
A8MPY1
Uniprot Name
Gamma-aminobutyric acid receptor subunit rho-3
Molecular Weight
54271.1 Da
References
  1. Walash MI, Belal F, Metwally ME, Hefnawy MM: A selective fluorimetric method for the determination of some 1,4-benzodiazepine drugs containing a hydroxyl group at C-3. J Pharm Biomed Anal. 1994 Nov;12(11):1417-23. [PubMed:7849137]

Drug created on August 29, 2007 11:43 / Updated on November 09, 2017 03:02