Halazepam

Identification

Name
Halazepam
Accession Number
DB00801
Description

Halazepam is a benzodiazepine derivative drug exerting anxiolytic, anticonvulsant, sedative, a muscle relaxing effects.1,2 It has been shown to be less toxic than chlordiazepoxide or diazepam.1 This drug is no longer marketed in the United States, and was withdrawn by Schering, its manufacturer, in 2009.3,4

Type
Small Molecule
Groups
Approved, Illicit, Withdrawn
Structure
Thumb
Weight
Average: 352.738
Monoisotopic: 352.059025338
Chemical Formula
C17H12ClF3N2O
Synonyms
  • Halazépam
  • Halazepam
  • Halazepamum
External IDs
  • Sch 12041
  • SCH-12041

Pharmacology

Indication

Used to relieve anxiety, nervousness, and tension associated with anxiety disorders.

Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
Learn More
Pharmacodynamics
Not Available
Mechanism of action

Benzodiazepines bind nonspecifically to benzodiazepine receptors BNZ1, which mediates sleep, and BNZ2, which affects affects muscle relaxation, anticonvulsant activity, motor coordination, and memory. As benzodiazepine receptors are thought to be coupled to gamma-aminobutyric acid-A (GABAA) receptors, this enhances the effects of GABA by increasing GABA affinity for the GABA receptor. Binding of GABA to the site opens the chloride channel, resulting in a hyperpolarized cell membrane that prevents further excitation of the cell.

TargetActionsOrganism
AGABA(A) Receptor
positive allosteric modulator
Humans
UGABA(A) Receptor Benzodiazepine Binding Site
ligand
Humans
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
Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
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
AcetazolamideThe risk or severity of adverse effects can be increased when Halazepam is combined with Acetazolamide.
AcetophenazineThe risk or severity of adverse effects can be increased when Halazepam is combined with Acetophenazine.
AclidiniumHalazepam may increase the central nervous system depressant (CNS depressant) activities of Aclidinium.
AgomelatineThe risk or severity of adverse effects can be increased when Halazepam is combined with Agomelatine.
AlfentanilThe risk or severity of adverse effects can be increased when Alfentanil is combined with Halazepam.
AlimemazineThe risk or severity of adverse effects can be increased when Halazepam is combined with Alimemazine.
AlmotriptanThe risk or severity of adverse effects can be increased when Halazepam is combined with Almotriptan.
AlosetronThe risk or severity of adverse effects can be increased when Halazepam is combined with Alosetron.
AlprazolamThe risk or severity of adverse effects can be increased when Alprazolam is combined with Halazepam.
AlverineThe risk or severity of adverse effects can be increased when Halazepam is combined with Alverine.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

    Learn more
  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

    Learn more
  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
Not Available

Products

International/Other Brands
Alapryl (Menarini) / Pacinone (Schering-Plough) / Paxipam (Schering-Plough)

Categories

ATC Codes
N05BA13 — Halazepam
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 / Benzene and substituted derivatives / Aryl chlorides / Tertiary carboxylic acid amides / Lactams / Ketimines / Propargyl-type 1,3-dipolar organic compounds / Azacyclic compounds / Organopnictogen compounds / Organofluorides
show 5 more
Substituents
1,4-benzodiazepine / Alkyl fluoride / Alkyl halide / Alpha-amino acid or derivatives / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide / Azacycle / Benzenoid / Carbonyl group
show 19 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Chemical Identifiers

UNII
320YC168LF
CAS number
23092-17-3
InChI Key
WYCLKVQLVUQKNZ-UHFFFAOYSA-N
InChI
InChI=1S/C17H12ClF3N2O/c18-12-6-7-14-13(8-12)16(11-4-2-1-3-5-11)22-9-15(24)23(14)10-17(19,20)21/h1-8H,9-10H2
IUPAC Name
7-chloro-5-phenyl-1-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one
SMILES
FC(F)(F)CN1C2=C(C=C(Cl)C=C2)C(=NCC1=O)C1=CC=CC=C1

References

Synthesis Reference

U.S. Patents 3,429,874 and 3,641,147.

General References
  1. Fann WE, Pitts WM, Wheless JC: Pharmacology, efficacy, and adverse effects of halazepam, a new benzodiazepine. Pharmacotherapy. 1982 Mar-Apr;2(2):72-9. [PubMed:6152591]
  2. Richards BL, Whittle SL, Buchbinder R: Muscle relaxants for pain management in rheumatoid arthritis. Cochrane Database Syst Rev. 2012 Jan 18;1:CD008922. doi: 10.1002/14651858.CD008922.pub2. [PubMed:22258993]
  3. Paxipam approval, FDA [Link]
  4. Federal drug register, FDA [Link]
Human Metabolome Database
HMDB0014939
KEGG Drug
D00338
PubChem Compound
31640
PubChem Substance
46508415
ChemSpider
29343
BindingDB
50408018
RxNav
26412
ChEBI
5603
ChEMBL
CHEMBL970
ZINC
ZINC000000537811
Therapeutic Targets Database
DAP000679
PharmGKB
PA164746526
Drugs.com
Drugs.com Drug Page
Wikipedia
Halazepam

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount

Pharmacoeconomics

Manufacturers
  • Schering corp sub schering plough corp
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)165 °CPhysProp
logP3.97SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility0.0017 mg/mLALOGPS
logP3.52ALOGPS
logP4.03ChemAxon
logS-5.3ALOGPS
pKa (Strongest Acidic)18.88ChemAxon
pKa (Strongest Basic)2.33ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area32.67 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity85.26 m3·mol-1ChemAxon
Polarizability31.82 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9952
Blood Brain Barrier+0.9966
Caco-2 permeable+0.6558
P-glycoprotein substrateSubstrate0.6489
P-glycoprotein inhibitor IInhibitor0.739
P-glycoprotein inhibitor IIInhibitor0.6548
Renal organic cation transporterInhibitor0.5819
CYP450 2C9 substrateNon-substrate0.7819
CYP450 2D6 substrateNon-substrate0.8422
CYP450 3A4 substrateSubstrate0.7404
CYP450 1A2 substrateInhibitor0.776
CYP450 2C9 inhibitorInhibitor0.5458
CYP450 2D6 inhibitorNon-inhibitor0.809
CYP450 2C19 inhibitorInhibitor0.7949
CYP450 3A4 inhibitorInhibitor0.5085
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7781
Ames testNon AMES toxic0.8369
CarcinogenicityNon-carcinogens0.7657
BiodegradationNot ready biodegradable1.0
Rat acute toxicity1.7143 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9836
hERG inhibition (predictor II)Inhibitor0.5729
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)MSsplash10-0fmi-3539000000-76854e3f82279b906a7f
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

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. [PubMed:23038269]
  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. [PubMed:29950725]
Kind
Protein group
Organism
Humans
Pharmacological action
Unknown
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. 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. [PubMed:29950725]
  2. 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. [PubMed:23038269]

Drug created on June 13, 2005 07:24 / Updated on June 12, 2020 10:51

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