Identification

Name
Fludiazepam
Accession Number
DB01567
Type
Small Molecule
Groups
Experimental, Illicit
Description

Fludiazepam is a drug which is a benzodiazepine derivative. It possesses anxiolytic, anticonvulsant, sedative and skeletal muscle relaxant properties. It is a scheduled drug in the U.S., but is approved for use in Japan.

Structure
Thumb
Synonyms
  • 7-chloro-5-(O-Fluorophenyl)-1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-one
  • Erispan
  • Fludiazepamum
International/Other Brands
Erispan (Sumitomo)
Categories
UNII
7F64A2K16Z
CAS number
3900-31-0
Weight
Average: 302.731
Monoisotopic: 302.062218928
Chemical Formula
C16H12ClFN2O
InChI Key
ROYOYTLGDLIGBX-UHFFFAOYSA-N
InChI
InChI=1S/C16H12ClFN2O/c1-20-14-7-6-10(17)8-12(14)16(19-9-15(20)21)11-4-2-3-5-13(11)18/h2-8H,9H2,1H3
IUPAC Name
7-chloro-5-(2-fluorophenyl)-1-methyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one
SMILES
CN1C2=C(C=C(Cl)C=C2)C(=NCC1=O)C1=CC=CC=C1F

Pharmacology

Indication

Used for the short-term treatment of anxiety disorders.

Pharmacodynamics

Fludiazepam is a benzodiazepine derivative. It possesses anxiolytic, anticonvulsant, sedative and skeletal muscle relaxant properties. Fludiazepam accumulates primarily in the cortex and thalamus.

Mechanism of action

Fludiazepam has similar action to diazepam, but binds with four times more affinity to benzodiazepine receptors than diazepam.

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
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Hepatic.

Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

Symptoms of overdose include drowsiness, weakness, nausea, dizziness, abdominal pain, cerebral oedema and renal tubular necrosis, hyperglycaemia and hypoglycaemia, liver damage, encephalopathy, coma and death.

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

Interactions

Drug Interactions
DrugInteraction
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when Fludiazepam is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3-isobutyl-1-methyl-7H-xanthineThe therapeutic efficacy of Fludiazepam can be decreased when used in combination with 3-isobutyl-1-methyl-7H-xanthine.
3,4-MethylenedioxyamphetamineThe risk or severity of adverse effects can be increased when 3,4-Methylenedioxyamphetamine is combined with Fludiazepam.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Fludiazepam.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Methoxyamphetamine is combined with Fludiazepam.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of adverse effects can be increased when Fludiazepam is combined with 5-methoxy-N,N-dimethyltryptamine.
6-O-benzylguanineThe therapeutic efficacy of Fludiazepam can be decreased when used in combination with 6-O-benzylguanine.
7-DeazaguanineThe therapeutic efficacy of Fludiazepam can be decreased when used in combination with 7-Deazaguanine.
7-NitroindazoleThe risk or severity of adverse effects can be increased when Fludiazepam is combined with 7-Nitroindazole.
7,9-DimethylguanineThe therapeutic efficacy of Fludiazepam can be decreased when used in combination with 7,9-Dimethylguanine.
Food Interactions
  • Avoid alcohol.
  • Avoid excessive quantities of coffee or tea (Caffeine).
  • Avoid taking with grapefruit juice.

References

Synthesis Reference

Yamamato, H., Inaba, S.,Okamoto, T., Hirohashi, T., Ishizumi, K., Yamamoto, M., Maruyama, l., Mori, K. and Kobayashi, T.; U.S. Patents 3,723,461; March 27, 1973; 3,828,027; August 6, 1974 and 3,925,364; December 9, 1975; all assigned to Sumitomo Chemical Co., Ltd.

General References
  1. Ishiwata K, Yanai K, Ido T, Miura-Kanno Y, Kawashima K: Synthesis and biodistribution of [11C]fludiazepam for imaging benzodiazepine receptors. Int J Rad Appl Instrum B. 1988;15(4):365-71. [PubMed:2855634]
  2. Nakatsuka I, Shimizu H, Asami Y, Katoh T, Hirose A, Yoshitake A: Benzodiazepines and their metabolites: relationship between binding affinity to the benzodiazepine receptor and pharmacological activity. Life Sci. 1985 Jan 14;36(2):113-9. [PubMed:2857046]
External Links
Human Metabolome Database
HMDB0015513
KEGG Drug
D01354
PubChem Compound
3369
PubChem Substance
46507563
ChemSpider
3252
ChEBI
31618
ChEMBL
CHEMBL13291
Therapeutic Targets Database
DAP000934
PharmGKB
PA164745609
Wikipedia
Fludiazepam
ATC Codes
N05BA17 — Fludiazepam

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
PropertyValueSource
melting point (°C)218.5-219Yamamato, H., Inaba, S.,Okamoto, T., Hirohashi, T., Ishizumi, K., Yamamoto, M., Maruyama, l., Mori, K. and Kobayashi, T.; U.S. Patents 3,723,461; March 27, 1973; 3,828,027; August 6, 1974 and 3,925,364; December 9, 1975; all assigned to Sumitomo Chemical Co., Ltd.
logP2.75HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.0144 mg/mLALOGPS
logP2.83ALOGPS
logP3.22ChemAxon
logS-4.3ALOGPS
pKa (Strongest Basic)1.89ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area32.67 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity80.03 m3·mol-1ChemAxon
Polarizability29.45 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9946
Caco-2 permeable+0.8567
P-glycoprotein substrateSubstrate0.6618
P-glycoprotein inhibitor IInhibitor0.5293
P-glycoprotein inhibitor IINon-inhibitor0.8532
Renal organic cation transporterInhibitor0.592
CYP450 2C9 substrateNon-substrate0.6724
CYP450 2D6 substrateNon-substrate0.9087
CYP450 3A4 substrateSubstrate0.8081
CYP450 1A2 substrateInhibitor0.7925
CYP450 2C9 inhibitorNon-inhibitor0.5446
CYP450 2D6 inhibitorNon-inhibitor0.8884
CYP450 2C19 inhibitorInhibitor0.5598
CYP450 3A4 inhibitorInhibitor0.5153
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5827
Ames testNon AMES toxic0.8792
CarcinogenicityNon-carcinogens0.817
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.2719 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9953
hERG inhibition (predictor II)Non-inhibitor0.8236
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
Mass Spectrum (Electron Ionization)MSsplash10-0uk9-2794000000-6f1a3e2e0783b2069f2f
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 fluorides / Aryl chlorides / Tertiary carboxylic acid amides / Lactams / Ketimines / Propargyl-type 1,3-dipolar organic compounds / Azacyclic compounds / Organopnictogen compounds
show 5 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 20 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
organofluorine compound, organochlorine compound, 1,4-benzodiazepinone (CHEBI:31618)

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. Nakatsuka I, Shimizu H, Asami Y, Katoh T, Hirose A, Yoshitake A: Benzodiazepines and their metabolites: relationship between binding affinity to the benzodiazepine receptor and pharmacological activity. Life Sci. 1985 Jan 14;36(2):113-9. [PubMed:2857046]
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. Nakatsuka I, Shimizu H, Asami Y, Katoh T, Hirose A, Yoshitake A: Benzodiazepines and their metabolites: relationship between binding affinity to the benzodiazepine receptor and pharmacological activity. Life Sci. 1985 Jan 14;36(2):113-9. [PubMed:2857046]
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. Nakatsuka I, Shimizu H, Asami Y, Katoh T, Hirose A, Yoshitake A: Benzodiazepines and their metabolites: relationship between binding affinity to the benzodiazepine receptor and pharmacological activity. Life Sci. 1985 Jan 14;36(2):113-9. [PubMed:2857046]
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. Nakatsuka I, Shimizu H, Asami Y, Katoh T, Hirose A, Yoshitake A: Benzodiazepines and their metabolites: relationship between binding affinity to the benzodiazepine receptor and pharmacological activity. Life Sci. 1985 Jan 14;36(2):113-9. [PubMed:2857046]
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. Nakatsuka I, Shimizu H, Asami Y, Katoh T, Hirose A, Yoshitake A: Benzodiazepines and their metabolites: relationship between binding affinity to the benzodiazepine receptor and pharmacological activity. Life Sci. 1985 Jan 14;36(2):113-9. [PubMed:2857046]
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. Nakatsuka I, Shimizu H, Asami Y, Katoh T, Hirose A, Yoshitake A: Benzodiazepines and their metabolites: relationship between binding affinity to the benzodiazepine receptor and pharmacological activity. Life Sci. 1985 Jan 14;36(2):113-9. [PubMed:2857046]
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. Nakatsuka I, Shimizu H, Asami Y, Katoh T, Hirose A, Yoshitake A: Benzodiazepines and their metabolites: relationship between binding affinity to the benzodiazepine receptor and pharmacological activity. Life Sci. 1985 Jan 14;36(2):113-9. [PubMed:2857046]
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. Nakatsuka I, Shimizu H, Asami Y, Katoh T, Hirose A, Yoshitake A: Benzodiazepines and their metabolites: relationship between binding affinity to the benzodiazepine receptor and pharmacological activity. Life Sci. 1985 Jan 14;36(2):113-9. [PubMed:2857046]
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. Nakatsuka I, Shimizu H, Asami Y, Katoh T, Hirose A, Yoshitake A: Benzodiazepines and their metabolites: relationship between binding affinity to the benzodiazepine receptor and pharmacological activity. Life Sci. 1985 Jan 14;36(2):113-9. [PubMed:2857046]
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. Nakatsuka I, Shimizu H, Asami Y, Katoh T, Hirose A, Yoshitake A: Benzodiazepines and their metabolites: relationship between binding affinity to the benzodiazepine receptor and pharmacological activity. Life Sci. 1985 Jan 14;36(2):113-9. [PubMed:2857046]
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. Nakatsuka I, Shimizu H, Asami Y, Katoh T, Hirose A, Yoshitake A: Benzodiazepines and their metabolites: relationship between binding affinity to the benzodiazepine receptor and pharmacological activity. Life Sci. 1985 Jan 14;36(2):113-9. [PubMed:2857046]
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. Nakatsuka I, Shimizu H, Asami Y, Katoh T, Hirose A, Yoshitake A: Benzodiazepines and their metabolites: relationship between binding affinity to the benzodiazepine receptor and pharmacological activity. Life Sci. 1985 Jan 14;36(2):113-9. [PubMed:2857046]
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. Nakatsuka I, Shimizu H, Asami Y, Katoh T, Hirose A, Yoshitake A: Benzodiazepines and their metabolites: relationship between binding affinity to the benzodiazepine receptor and pharmacological activity. Life Sci. 1985 Jan 14;36(2):113-9. [PubMed:2857046]
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. Nakatsuka I, Shimizu H, Asami Y, Katoh T, Hirose A, Yoshitake A: Benzodiazepines and their metabolites: relationship between binding affinity to the benzodiazepine receptor and pharmacological activity. Life Sci. 1985 Jan 14;36(2):113-9. [PubMed:2857046]
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. Nakatsuka I, Shimizu H, Asami Y, Katoh T, Hirose A, Yoshitake A: Benzodiazepines and their metabolites: relationship between binding affinity to the benzodiazepine receptor and pharmacological activity. Life Sci. 1985 Jan 14;36(2):113-9. [PubMed:2857046]
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. Nakatsuka I, Shimizu H, Asami Y, Katoh T, Hirose A, Yoshitake A: Benzodiazepines and their metabolites: relationship between binding affinity to the benzodiazepine receptor and pharmacological activity. Life Sci. 1985 Jan 14;36(2):113-9. [PubMed:2857046]

Drug created on July 31, 2007 07:10 / Updated on November 02, 2018 05:03