Lormetazepam

Identification

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Name
Lormetazepam
Accession Number
DB13872
Type
Small Molecule
Groups
Approved
Description

Lormatazepam is an orally available benzodiazepine used in the UK for the treatment of short-term insomnia 2. It is marketed by Auden Mckenzie (Pharma Division) in 0.5 and 1 mg tablet formulations.

Structure
Thumb
Synonyms
  • (±)-Lormetazepam
  • (RS)-Lormetazepam
  • 7-Chloro-1,3-dihydro-5-(o-chlorophenyl)-3-hydroxy-1-methyl-2H-1,4-benzodiazepin-2-one
  • 7-Chloro-5-(2-chlorophenyl)-1,3-dihydro-3-hydroxy-1-methyl-2H-1,4-benzodiazepin-2-one
  • Methyllorazepam
  • N-Methyllorazepam
Categories
UNII
GU56C842ZA
CAS number
848-75-9
Weight
Average: 335.185
Monoisotopic: 334.027583052
Chemical Formula
C16H12Cl2N2O2
InChI Key
FJIKWRGCXUCUIG-UHFFFAOYSA-N
InChI
InChI=1S/C16H12Cl2N2O2/c1-20-13-7-6-9(17)8-11(13)14(19-15(21)16(20)22)10-4-2-3-5-12(10)18/h2-8,15,21H,1H3
IUPAC Name
7-chloro-5-(2-chlorophenyl)-3-hydroxy-1-methyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one
SMILES
CN1C2=C(C=C(Cl)C=C2)C(=NC(O)C1=O)C1=CC=CC=C1Cl

Pharmacology

Indication

For the treatment of short-term insomnia 2

Pharmacodynamics

Lormetazepam is a benzodiazepine which reduces central nervous system (CNS) activity 2,1. It produces anxiolytic, muscle relaxant, sedative and hypnotic effects. Because it is a short-acting benzodiapine, it does not produce significant sedation after waking.

Mechanism of action

Lormetazepam, as a benzodiazepine, binds to the regulatory site between the α and γ subunits of γ-aminobutryic acid (GABA) A receptors with γ2 and α1, α2, α3, or α5 subunits 1. This facilitates the opening of the chloride channel allowing chloride ions to flow into the neuron resulting in hyperpolarization. Hyperpolarized neurons require greater simulation to reach their action potential threshold. The general inhibitory effect on neuronal depolarization produces the effects of lormetazepam.

TargetActionsOrganism
AGamma-aminobutyric acid receptor subunit alpha-2
positive allosteric modulator
Humans
AGamma-aminobutyric acid receptor subunit gamma-2
positive allosteric modulator
Humans
AGamma-aminobutyric acid receptor subunit alpha-3
positive allosteric modulator
Humans
AGamma-aminobutyric acid receptor subunit alpha-5
positive allosteric modulator
Humans
AGamma-aminobutyric acid receptor subunit alpha-1
positive allosteric modulator
Humans
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Metabolised to an inactive metabolite via glucuronide conjugation 2

Route of elimination
Not Available
Half life

The terminal phase half life is 11 h 2.

Clearance
Not Available
Toxicity

The primary manifestation of overdosage ranges from drowsiness to coma and symptoms may include ataxia, hypotension, hypotonia, respiratory depression which may lead to death 2.

Experimental LD50 values are as follows 3: Mouse - 780 mg/kg (intraperitoneal), 1790 mg/kg (oral), 10000 mg/kg (subcutaneous). Rat - 6250 mg/kg (intraperitoneal), 10000 mg/kg (oral), 10000 mg/kg (intraperitoneal).

Affected organisms
Not Available
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 Lormetazepam is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3-isobutyl-1-methyl-7H-xanthineThe therapeutic efficacy of Lormetazepam can be decreased when used in combination with 3-isobutyl-1-methyl-7H-xanthine.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Lormetazepam.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Methoxyamphetamine is combined with Lormetazepam.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of adverse effects can be increased when Lormetazepam is combined with 5-methoxy-N,N-dimethyltryptamine.
6-O-benzylguanineThe therapeutic efficacy of Lormetazepam can be decreased when used in combination with 6-O-benzylguanine.
7-DeazaguanineThe therapeutic efficacy of Lormetazepam can be decreased when used in combination with 7-Deazaguanine.
7-NitroindazoleThe risk or severity of adverse effects can be increased when 7-Nitroindazole is combined with Lormetazepam.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineThe risk or severity of adverse effects can be increased when 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline is combined with Lormetazepam.
7,9-DimethylguanineThe therapeutic efficacy of Lormetazepam can be decreased when used in combination with 7,9-Dimethylguanine.
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.

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  • Action
    Action

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Food Interactions
Not Available

References

General References
  1. 43. (2012). In Rang and Dale's Pharmacology (7th ed., pp. 533-534). Edinburgh: Elsevier/Churchill Livingstone. [ISBN:978-0-7020-3471-8]
  2. MRHA: Lormetazepam Summary of Product Characteristics [Link]
  3. ChemIDPlus: Lormetazepam [Link]
External Links
Human Metabolome Database
HMDB0041919
PubChem Compound
13314
PubChem Substance
347829324
ChemSpider
12750
ChEBI
52993
ChEMBL
CHEMBL22097
Wikipedia
Lormetazepam
ATC Codes
N05CD06 — Lormetazepam
MSDS
Download (49.8 KB)

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 Solubility0.0164 mg/mLALOGPS
logP2.92ALOGPS
logP3.39ChemAxon
logS-4.3ALOGPS
pKa (Strongest Acidic)10.68ChemAxon
pKa (Strongest Basic)-2.2ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area52.9 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity85.82 m3·mol-1ChemAxon
Polarizability32.21 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - EI-BGC-MSsplash10-0a4i-1219000000-503deaa645713d28cd79
Mass Spectrum (Electron Ionization)MSsplash10-0a4i-2739000000-db8dc59f3b0cd2b1f961
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 / Chlorobenzenes / Aryl chlorides / Tertiary carboxylic acid amides / Lactams / Ketimines / Propargyl-type 1,3-dipolar organic compounds / Azacyclic compounds / Alkanolamines / Organopnictogen compounds
show 4 more
Substituents
1,4-benzodiazepine / Alpha-amino acid or derivatives / Chlorobenzene / Halobenzene / Aryl chloride / Aryl halide / Monocyclic benzene moiety / Benzenoid / Tertiary carboxylic acid amide / Carboxamide group
show 19 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
organochlorine compound, 1,4-benzodiazepinone (CHEBI:52993)

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Positive allosteric modulator
Curator comments
Facilitates opening of the chloride channel.
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. Rang, H. P. and Dale, M. M. (2012). Rang and Dale's Pharmacology (7th ed.). Edinburgh: Elsevier/Churchill Livingstone. [ISBN:978-0-7020-3471-8]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Positive allosteric modulator
Curator comments
Facilitates opening of the chloride channel.
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. Rang, H. P. and Dale, M. M. (2012). Rang and Dale's Pharmacology (7th ed.). Edinburgh: Elsevier/Churchill Livingstone. [ISBN:978-0-7020-3471-8]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Positive allosteric modulator
Curator comments
Facilitates opening of the chloride channel.
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. Rang, H. P. and Dale, M. M. (2012). Rang and Dale's Pharmacology (7th ed.). Edinburgh: Elsevier/Churchill Livingstone. [ISBN:978-0-7020-3471-8]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Positive allosteric modulator
Curator comments
Facilitates opening of the chloride channel.
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. Rang, H. P. and Dale, M. M. (2012). Rang and Dale's Pharmacology (7th ed.). Edinburgh: Elsevier/Churchill Livingstone. [ISBN:978-0-7020-3471-8]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Positive allosteric modulator
Curator comments
Facilitates opening of the chloride channel.
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. Rang, H. P. and Dale, M. M. (2012). Rang and Dale's Pharmacology (7th ed.). Edinburgh: Elsevier/Churchill Livingstone. [ISBN:978-0-7020-3471-8]

Drug created on July 07, 2017 15:36 / Updated on May 01, 2019 11:53